An Efficacy and Safety Study of AG-221 (CC-90007) Versus... | NCT02577406 | Trialant
NCT02577406
Sponsor
Celgene
Status
Completed
Last Update Posted
May 18, 2025Actual
Enrollment
319Actual
Phase
Phase 3
Conditions
Leukemia, Myeloid
Isocitrate Dehydrogenase
Interventions
AG-221
BSC
Azacitidine
Low-dose cytarabine (LDAC)
Intermediate-dose cytarabine (IDAC)
Countries
United States
Australia
Austria
Belgium
Brazil
Canada
China
Czechia
Denmark
France
Germany
Italy
Russia
South Korea
Spain
Taiwan
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02577406
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
AG-221-AML-004
Secondary IDs
Not provided
Brief Title
An Efficacy and Safety Study of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation
Official Title
A Phase 3, Multicenter, Open-label, Randomized Study Comparing the Efficacy and Safety of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation
Acronym
IDHENTIFY
Organization
CelgeneINDUSTRY
Status Module
Record Verification Date
May 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
YesNCT03723057No longer available
Start Date
Dec 30, 2015Actual
Primary Completion Date
Mar 17, 2020Actual
Completion Date
Mar 25, 2024Actual
First Submitted Date
Oct 14, 2015
First Submission Date that Met QC Criteria
Oct 14, 2015
First Posted Date
Oct 16, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 29, 2022
Results First Submitted that Met QC Criteria
Aug 17, 2022
Results First Posted Date
Sep 10, 2022Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 5, 2025
Last Update Posted Date
May 18, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
CelgeneINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is an international, multicenter, open-label, randomized, Phase 3 study comparing the efficacy and safety of AG-221 versus conventional care regimens (CCRs) in subjects 60 years or older with acute myeloid leukemia (AML) refractory to or relapsed after second- or third-line AML therapy and positive for an isocitrate dehydrogenase (IDH2) mutation.
Detailed Description
Acute myeloid leukaemia (AML) is a form of cancer that is common in older patients. Mutations in the isocitrate dehydrogenase enzyme 2 (IDH2) have been found in approximately 15% of patients with AML.
The outcome of first line chemotherapy treatment is poor and many patients fail to attain complete remission (CR, ie refractory) or will eventually relapse. There is no single standard of care for relapsed or refractory AML. Since the prognosis is very poor there is a great need for new therapies.
Inhibition of the mutant IDH2 enzyme may represent a promising targeted therapy for AML. AG-221 is a small molecule inhibitor of the IDH2 enzyme, designed to preferentially target the mutant IDH2 variants. Data from the ongoing first-in-human study has shown AG-221 to be generally well tolerated and demonstrated CR in patients with IDH2 mutation positive relapsed or refractory AML.
The study purpose is to test the safety and efficacy of AG-221 compared with conventional care regimens (CCR), which include best supportive care (BSC) only, azacitidine plus BSC, low-dose cytarabine plus BSC or intermediate-dose cytarabine plus BSC, in patients with late stage AML refractory to or relapsed after second or third line therapy and positive for the IDH2 mutation. Patients will be randomly assigned to receive open-label tablets of AG-221 or one of the CCR on continuous 28-day treatment cycles. The trial duration is expected to be 78 months which includes 42 months enrollment, approximately 7 months treatment and a follow-up period.
Study procedures include: vital signs, physical exams, ECGs, ECHO, urine/blood samples, bone marrow aspirates and/or biopsies and peripheral blood to test for IDH2 and assess treatment response. Bone marrow, blood, cheek swab samples will be used for genetic tests.
This study is being sponsored by Celgene Corporation. Approximately 316 participants will take part in the study.
Conditions Module
Conditions
Leukemia, Myeloid
Isocitrate Dehydrogenase
Keywords
AG-221
CC-90007
Efficacy
Safety
Leukemia
Acute myeloid meukemia
Isocitrate dehydrogenase 2 mutation
Enasidenib
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
319Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
AG-221 plus Best supportive care (BSC)
Experimental
Continuous 28-day cycles of AG 221 100 mg orally (PO) once a day (QD) for 28 days, plus BSC.
Drug: AG-221
Other: BSC
Conventional care regimen (CCR)
Active Comparator
Continuous 28-day cycles of BSC only, azacitidine subcutaneously (SC) plus BSC, low-dose cytarabine (LDAC) SC plus BSC, or intermediate-dose cytarabine (IDAC) intravenously (IV) plus BSC. Subjects will be assigned by the investigator to one of the CCR treatment options based on the investigator's assessment of subjects' eligibility.
Other: BSC
Drug: Azacitidine
Drug: Low-dose cytarabine (LDAC)
Drug: Intermediate-dose cytarabine (IDAC)
Interventions
Name
Type
Description
Arm Group Labels
Other Names
AG-221
Drug
Continuous 28-day cycles of AG 221 100 mg orally (PO) once a day (QD) for 28 days
AG-221 plus Best supportive care (BSC)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Overall Survival (OS)
The time between randomization and death from any cause. Participants who drop-out or are alive at the end of trial will have their OS times censored at the time of last contact, as appropriate.
From randomization to death due to any cause (up to approximately 49 months)
Secondary Outcomes
Measure
Description
Time Frame
Overall Response Rate
Number of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
Subject is ≥ 60 years of age at the time of signing the ICF
Subject has primary (ie, de novo) or secondary (progression of MDS or myeloproliferative neoplasms ([MPN], or therapy-related) AML according to WHO classification (Appendix B)
Subject has received second- or third-line of AML therapy (see Appendix G for the definition of prior AML line; note that, for subjects having AML secondary to prior higher risk [Intermediate-2 or High risk according to the International Prognostic Scoring System] MDS treated with a hypomethylating agent [eg, azacitidine or decitabine], the hypomethylating therapy can be counted as a line if there is disease progression to AML during or shortly [eg, within 60 days] after the hypomethylating therapy.)
Subject has the following disease status:
Refractory to or relapsed after second- or third-line of intensive therapy for AML (eg, the "7 + 3" regimen):
at least 5% leukemic blasts in bone marrow (the minimum number of treatment cycles of the intensive therapy is per the investigator's discretion); or
Refractory to or relapsed after second- or third-line low-intensity AML therapy (eg, LDAC, azacitidine or decitabine):
at least 5% leukemic blasts in bone marrow after at least 2 treatment cycles
Subject is eligible for and willing to receive the pre-selected CCR treatment option, according to the investigator's assessment (Note: Subjects with degenerative and toxic encephalopathies, especially after the use of methotrexate or treatment with ionizing radiation, should not receive cytarabine.)
Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix D)
Subject has IDH2 gene mutations tested centrally (using the "investigational use only"PCR assay, Abbott RealTime IDH2) in samples of bone marrow aspirate and peripheral blood, and confirmed positive in bone marrow aspirate and/or peripheral blood. (Note: in the event that the central laboratory result is delayed and precludes acute clinical management of a subject who has confirmed IDH2 gene mutation by local evaluation, the subject may be eligible for randomization with approval by the Medical Monitor.)
Subject has adequate organ function defined as:
Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, following review by the Medical Monitor; and
Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome (eg, a gene mutation in UGT1A1) or leukemic organ involvement, following review by the Medical Monitor; and
Creatinine clearance > 30 mL/min based on the Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR):
GFR (mL/min/1.73 m2) = 175 × (serum creatinine)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)
Females of childbearing potential (FCBP)* may participate, providing they meet the following conditions:
Agree to practice true abstinence from sexual intercourse or to use highly effective contraceptive methods (eg, combined [containing estrogen and progestogen] or progestogen-only associated with inhibition of ovulation, oral, injectable, intravaginal, patch, or implantable hormonal contraceptive; bilateral tubal occlusion; intra-uterine device; intrauterine hormone-releasing system; or male partner sterilization [note that vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the FCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success]) at screening and throughout the study, and for 4 months following the last study treatment (6 months following the last dose of cytarabine); and
Have a negative serum β-subunit of human chorionic gonadotropin (β-hCG) pregnancy test (sensitivity of at least 25 mIU/mL) at screening; and
Have a negative serum or urine (investigator's discretion under local regulations) β-hCG pregnancy test (sensitivity of at least 25 mIU/mL) within 72 hours prior to the start of study treatment in the Treatment Phase (note that the screening serum pregnancy test can be used as the test prior to the start of study treatment in the Treatment Phase if it is performed within the 72-hour timeframe).
Male subjects must agree to practice true abstinence from sexual intercourse or to the use of highly effective contraceptive methods (as described above) with non-pregnant female partners of childbearing potential at screening and throughout the course of the study, and should avoid conception with their partners during the course of the study and for 4 months following the last study treatment (6 months following the last dose of cytarabine; 6 months following the last dose of azacitidine in Canada)
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
Subject is willing and able to adhere to the study visit schedule and other protocol requirements
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
Subject is suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype
Subject has AML secondary to chronic myelogenous leukemia
Subject has received a targeted agent against an IDH2 mutation
Subject has received systemic anticancer therapy or radiotherapy < 14 days prior to the start of study treatment. Note that hydroxyurea is allowed prior to the start of study treatment for the control of leukocytosis (however, hydroxyurea should not be given within 72 hours prior to and after administration of azacitidine).
Subject has received non-cytotoxic or investigational agents < 14 days or 5 half-lives, whichever is longer, prior to the start of study treatment
Subject has undergone HSCT within 60 days prior to the start of study treatment, or on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of a stable dose of oral steroid post-HSCT and/or topical steroids for ongoing skin GVHD is permitted.
Subject has persistent, clinically significant non-hematologic toxicities from prior therapies
Subject has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening.
Subject has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
Subject has immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
Subject has significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) class III or IV congestive heart failure (Appendix E); acute coronary syndrome (ACS); and/or stroke; or left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment
Subject has prior history of malignancy, other than MDS, MPN or AML, unless the subject has been free of the disease for ≥ 1 year prior to the start of study treatment.
However, subjects with the following history/concurrent conditions are allowed:
Basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis clinical staging system)
Subject is known seropositive or active infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
Subjects has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg)
Subject is a pregnant or lactating female
Subject has known or suspected to have hypersensitivity to any of the components of study treatment
Subject is taking those medications (listed in Section 8.2) that are known to prolong QT interval unless the subject can be transferred to other medications at least 5 half-lives prior to the start of study treatment
Subject has QTc interval (ie, Fridericia's correction [QTcF]) ≥ 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval syndrome) at screening
Subject is taking the following sensitive CYP substrate medications that have a narrow therapeutic range are excluded from the study unless the subject can be transferred to other medications at least 5 half-lives prior to the start of study treatment: paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2)
Subject is taking the breast cancer resistance protein (BCRP) transporter-sensitive substrate rosuvastatin should be excluded from the study unless the subject can be transferred to other medications at least 5 half-lives prior to the start of study treatment
Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Subject has any condition that confounds the ability to interpret data from the study
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
60 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Bristol-Myers Squibb
Bristol-Myers Squibb
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Local Institution - 121
Miami
Florida
33136
United States
University of Florida Health Cancer Center at Orlando Health
319 participants were randomized and 298 participants received treatment
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
FG001
Conventional Care Regimens (CCRs)
Periods
Title
Milestones
Reasons Not Completed
Randomized Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Nov 30, 2017
Jun 29, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
BSC
Other
Best supportive care includes, hydroxyurea for leukocytosis and/or differentiation-like syndrome, anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support
AG-221 plus Best supportive care (BSC)
Conventional care regimen (CCR)
Azacitidine
Drug
continuous 28-day cycles of azacitidine 75 mg/m2/day SC for 7 days, plus BSC
Conventional care regimen (CCR)
Low-dose cytarabine (LDAC)
Drug
continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC
Conventional care regimen (CCR)
Intermediate-dose cytarabine (IDAC)
Drug
28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after IDAC therapy concludes per standard institutional practice
Conventional care regimen (CCR)
From randomization up to study completion (approximately 78 months)
Event-Free Survival
Time from randomization to documented morphologic relapse after complete remission/complete remission with incomplete neutrophil recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp), progressive disease (PD) or death from any cause, whichever occurs first. Morphologic Relapse after CR/CRi/CRp is defined as either reappearance of ≥ 5% blasts in the BM not attributable to any other cause or the development of extramedullary disease. PD is defined as a > 50% increase of BM blast count percentage from baseline to ≥ 20% for participants with 5 to 70% BM blasts at baseline or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10 x 109/L (10,000/μL) for participants with > 70% BM blasts at baseline or the development of new extramedullary disease.
From randomization up to study completion (approximately 78 months)
Duration of Response
Time from first documented MLFS/CR/CRi/CRp/PR to documented morphologic relapse after CR/CRi/CRp/ PD or death due to any cause, whichever occurs first. CR and MLFS are defined as <5% blasts in a BM aspirate sample with marrow spicules + a count of ≥200 nucleated cells with no blasts with Auer rods + no extramedullary disease. CR must also include: ANC ≥ 1,000/μL, Platelet count ≥100,000/μL, + independent of red cell transfusions for ≥1 week before assessment. CRi is all criteria of CR except ANC. CRp is all criteria of CR except platelet count. PR is defined as all hematologic criteria of CR with >50% decrease in BM blasts to 5%-25%. Relapse after CR/CRi/CRp is defined as reappearance of ≥ 5% blasts in the BM not attributable to other cause or development of extramedullary disease. PD is defined as > 50% increase of BM blast count from baseline to ≥ 20% or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10,000/μL or development of new extramedullary disease.
From randomization up to study completion (approximately 78 months)
Time to Response
Time from randomization to first documented MLFS/CR/CRi/CRp/PR. Complete remission (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
From randomization to to first documented MLFS/CR/CRi/CRp/PR (up to approximately 49 months)
Treatment Mortality at 30 Days
The number of participant deaths from any cause within 30 days of initiation of study treatment.
From first dose to 30 days after first dose
Treatment Mortality at 60 Days
The number of participant deaths from any cause within 60 days of initiation of study treatment.
From first dose to 60 days after first dose
One-Year Survival Rate
The proportion of participants alive at 1 year after randomization
From randomization up to 1 year post (approximately 12 months)
Overall Remission Rate
The number of participants with CR + CRi + CRp according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria. Complete remission (CR) is defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count.
From randomization up to approximately 49 months
Complete Remission Rate
The number of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML). CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease; plus the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment.
From randomization up to approximately 49 months
Hematologic Improvement Rate
The number of participants with hematologic improvement neutrophil response (HI-N) + hematologic improvement platelet response (HI-P) + hematologic improvement erythroid response (HI-E) according to the International Working Group for Myelodysplastic Syndromes for Hematologic Improvement (IWG MDS HI) criteria. HI-E is defined as a hemoglobin increase by ≥ 1.5 g/dL and a relevant reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. HI-P is defined as an absolute increase of ≥ 30 X 10^9/L for participants starting with > 20 X and an increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-N is defined as At least 100% increase and an absolute increase > 0.5 X 10^9/L.
From randomization up to approximately 49 months
The Number of Participants That Underwent Hematopoietic Stem Cell Transplantation (HSCT)
The number of participants that underwent hematopoietic stem cell transplantation during the study.
From randomization up to approximately 49 months
Time to Treatment Failure
Time from randomization to discontinuation of study treatment due to any cause
From randomization to discontinuation of study treatment due to any cause (up to approximately 49 months)
The Number of Participants Experiencing Adverse Events (AEs)
The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (SAE) is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or constitutes an important medical event. All AEs were coded using the MedDRA Version 22.0. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). A treatment-related TEAE was defined as a TEAE that was suspected by the investigator to be related to study treatment. The severity was graded by the study personnel based on NCI National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
From randomization up to study completion (approximately 78 months)
The Percent of Participants Experiencing Clinically Significant Laboratory Abnormalities - Serum Chemistry
The percent of participants with clinically significant serum chemistry laboratory abnormalities. A clinically significant laboratory abnormality is defined as meeting Grade 3 or Grade 4 criteria according to the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is defined as severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. The chemistry panel includes sodium, potassium, calcium, magnesium, chloride, phosphorus, CO2, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, albumin, total protein, alkaline phosphatase (ALP), bilirubin (total and direct), uric acid, lactate dehydrogenase (LDH), AST/SGOT, ALT/SGPT, gamma glutamyl transpeptidase (GGT), amylase and lipase.
From first dose up to approximately 49 months
The Percent of Participants Experiencing Clinically Significant Laboratory Abnormalities - Hematology
The percent of participants with clinically significant hematology laboratory abnormalities. A clinically significant laboratory abnormality is defined as meeting Grade 3 or Grade 4 criteria according to the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is defined as severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. The hematology panel includes complete blood count (CBC) with differential, including red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC) count (with differential), absolute neutrophil count (ANC) and platelet count.
From first dose up to approximately 49 months
The Percent of Participants Experiencing Clinically Significant Vital Sign Abnormalities
The percent of participants with clinically significant vital sign abnormalities including weight, temperature, blood pressure, pulse rate, and respiratory rate.
From first dose up to approximately 49 months
The Percentage of Participants Experiencing Clinically Significant Electrocardiogram (ECG) Abnormalities
The percent of participants with clinically significant ECG abnormalities. 12-lead ECG was assessed by a physician trained in ECG interpretation. Intervals including PR, QRS, QT and RR were collected, as well as heart rate and rhythm.
From first dose up to approximately 49 months
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)
The change from baseline in the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered meaningful. Results obtained just prior to the start of study treatment on Day 1 of Cycle 1 will serve as the baseline values. If not available, the most recent screening results prior to the start of study treatment on Day 1 of Cycle 1 will be considered the baseline values.
From baseline to cycle 2 day 1 (up to approximately 1 month)
Change From Baseline in EQ-5D-5L Health Utility Index
The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values.
From baseline up to cycle 2 day 1 (up to approximately 1 month)
Orlando
Florida
32806
United States
Local Institution - 111
Chicago
Illinois
60637
United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack
New Jersey
07601
United States
Roswell Park Cancer Institute
Buffalo
New York
14263
United States
Local Institution - 128
New York
New York
10029
United States
Strong Health System
Rochester
New York
14642
United States
Montefiore Medical Center Albert Einstein Cancer Center
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC: Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
FG000158 subjects
FG001161 subjects
COMPLETED
Continuing to treatment period
FG000157 subjects
FG001141 subjects
NOT COMPLETED
FG0001 subjects
FG00120 subjects
Type
Comment
Reasons
Death
FG0001 subjects
FG0010 subjects
Other reasons
FG0000 subjects
FG00120 subjects
Treatment Period
Type
Comment
Milestone Data
STARTED
FG000157 subjects
FG001141 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
NOT COMPLETED
FG000157 subjects
FG001141 subjects
Type
Comment
Reasons
Death
FG00038 subjects
FG00123 subjects
Adverse Event
FG00017 subjects
FG001
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
BG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC: Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000158
BG001161
BG002319
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00071.4± 6.04
BG00170.5± 6.17
BG00270.9± 6.11
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
≥ 60 to < 70 years
BG00061
BG00172
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00067
BG00165
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0004
BG0013
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Overall Survival (OS)
The time between randomization and death from any cause. Participants who drop-out or are alive at the end of trial will have their OS times censored at the time of last contact, as appropriate.
All randomized participants
Posted
Median
95% Confidence Interval
Months
From randomization to death due to any cause (up to approximately 49 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC: Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG0006.5(5.5 to 9.5)
OG0016.2(4.6 to 7.7)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Stratified Log Rank
0.2288
Hazard Ratio (HR)
0.86
2-Sided
95
0.67
1.10
The hazard ratio was from a Cox proportional hazards model stratified by prior intensive therapy for AML and primary refractory
Superiority
Secondary
Overall Response Rate
Number of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
All randomized participants
Posted
Count of Participants
Participants
From randomization up to study completion (approximately 78 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Event-Free Survival
Time from randomization to documented morphologic relapse after complete remission/complete remission with incomplete neutrophil recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp), progressive disease (PD) or death from any cause, whichever occurs first. Morphologic Relapse after CR/CRi/CRp is defined as either reappearance of ≥ 5% blasts in the BM not attributable to any other cause or the development of extramedullary disease. PD is defined as a > 50% increase of BM blast count percentage from baseline to ≥ 20% for participants with 5 to 70% BM blasts at baseline or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10 x 109/L (10,000/μL) for participants with > 70% BM blasts at baseline or the development of new extramedullary disease.
All randomized participants
Posted
Median
95% Confidence Interval
Months
From randomization up to study completion (approximately 78 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Duration of Response
Time from first documented MLFS/CR/CRi/CRp/PR to documented morphologic relapse after CR/CRi/CRp/ PD or death due to any cause, whichever occurs first. CR and MLFS are defined as <5% blasts in a BM aspirate sample with marrow spicules + a count of ≥200 nucleated cells with no blasts with Auer rods + no extramedullary disease. CR must also include: ANC ≥ 1,000/μL, Platelet count ≥100,000/μL, + independent of red cell transfusions for ≥1 week before assessment. CRi is all criteria of CR except ANC. CRp is all criteria of CR except platelet count. PR is defined as all hematologic criteria of CR with >50% decrease in BM blasts to 5%-25%. Relapse after CR/CRi/CRp is defined as reappearance of ≥ 5% blasts in the BM not attributable to other cause or development of extramedullary disease. PD is defined as > 50% increase of BM blast count from baseline to ≥ 20% or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10,000/μL or development of new extramedullary disease.
All participants who achieved CR/CRi/CRp/PR/MLFS
Posted
Median
95% Confidence Interval
Months
From randomization up to study completion (approximately 78 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Time to Response
Time from randomization to first documented MLFS/CR/CRi/CRp/PR. Complete remission (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
All participants who achieved CR/CRi/CRp/PR/MLFS
Posted
Median
Full Range
Days
From randomization to to first documented MLFS/CR/CRi/CRp/PR (up to approximately 49 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Treatment Mortality at 30 Days
The number of participant deaths from any cause within 30 days of initiation of study treatment.
All randomized participants
Posted
Count of Participants
Participants
From first dose to 30 days after first dose
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Treatment Mortality at 60 Days
The number of participant deaths from any cause within 60 days of initiation of study treatment.
All randomized participants
Posted
Count of Participants
Participants
From first dose to 60 days after first dose
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
One-Year Survival Rate
The proportion of participants alive at 1 year after randomization
All randomized participants
Posted
Number
95% Confidence Interval
Proportion of participants
From randomization up to 1 year post (approximately 12 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Overall Remission Rate
The number of participants with CR + CRi + CRp according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria. Complete remission (CR) is defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count.
All randomized participants
Posted
Count of Participants
Participants
From randomization up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Complete Remission Rate
The number of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML). CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease; plus the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment.
All randomized participants
Posted
Count of Participants
Participants
From randomization up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Hematologic Improvement Rate
The number of participants with hematologic improvement neutrophil response (HI-N) + hematologic improvement platelet response (HI-P) + hematologic improvement erythroid response (HI-E) according to the International Working Group for Myelodysplastic Syndromes for Hematologic Improvement (IWG MDS HI) criteria. HI-E is defined as a hemoglobin increase by ≥ 1.5 g/dL and a relevant reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. HI-P is defined as an absolute increase of ≥ 30 X 10^9/L for participants starting with > 20 X and an increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-N is defined as At least 100% increase and an absolute increase > 0.5 X 10^9/L.
All randomized participants
Posted
Count of Participants
Participants
From randomization up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
The Number of Participants That Underwent Hematopoietic Stem Cell Transplantation (HSCT)
The number of participants that underwent hematopoietic stem cell transplantation during the study.
All randomized participants
Posted
Count of Participants
Participants
From randomization up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Time to Treatment Failure
Time from randomization to discontinuation of study treatment due to any cause
All randomized participants
Posted
Median
95% Confidence Interval
Months
From randomization to discontinuation of study treatment due to any cause (up to approximately 49 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
The Number of Participants Experiencing Adverse Events (AEs)
The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (SAE) is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or constitutes an important medical event. All AEs were coded using the MedDRA Version 22.0. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). A treatment-related TEAE was defined as a TEAE that was suspected by the investigator to be related to study treatment. The severity was graded by the study personnel based on NCI National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
All treated participants
Posted
Count of Participants
Participants
From randomization up to study completion (approximately 78 months)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
The Percent of Participants Experiencing Clinically Significant Laboratory Abnormalities - Serum Chemistry
The percent of participants with clinically significant serum chemistry laboratory abnormalities. A clinically significant laboratory abnormality is defined as meeting Grade 3 or Grade 4 criteria according to the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is defined as severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. The chemistry panel includes sodium, potassium, calcium, magnesium, chloride, phosphorus, CO2, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, albumin, total protein, alkaline phosphatase (ALP), bilirubin (total and direct), uric acid, lactate dehydrogenase (LDH), AST/SGOT, ALT/SGPT, gamma glutamyl transpeptidase (GGT), amylase and lipase.
All treated participants
Posted
Number
Percent of Participants
From first dose up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
The Percent of Participants Experiencing Clinically Significant Laboratory Abnormalities - Hematology
The percent of participants with clinically significant hematology laboratory abnormalities. A clinically significant laboratory abnormality is defined as meeting Grade 3 or Grade 4 criteria according to the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is defined as severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. The hematology panel includes complete blood count (CBC) with differential, including red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC) count (with differential), absolute neutrophil count (ANC) and platelet count.
All treated participants
Posted
Number
Percent of Participants
From first dose up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
The Percent of Participants Experiencing Clinically Significant Vital Sign Abnormalities
The percent of participants with clinically significant vital sign abnormalities including weight, temperature, blood pressure, pulse rate, and respiratory rate.
All treated participants
Posted
Number
Percent of Participants
From first dose up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
The Percentage of Participants Experiencing Clinically Significant Electrocardiogram (ECG) Abnormalities
The percent of participants with clinically significant ECG abnormalities. 12-lead ECG was assessed by a physician trained in ECG interpretation. Intervals including PR, QRS, QT and RR were collected, as well as heart rate and rhythm.
All treated participants with evaluable measurements
Posted
Number
Percentage of Participants
From first dose up to approximately 49 months
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)
The change from baseline in the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered meaningful. Results obtained just prior to the start of study treatment on Day 1 of Cycle 1 will serve as the baseline values. If not available, the most recent screening results prior to the start of study treatment on Day 1 of Cycle 1 will be considered the baseline values.
All participants who completed at least 15 of the 30 items at baseline and at least one post-baseline assessment based on EORTC QLQ-C30
Posted
Mean
Standard Deviation
Change from baseline in QLQ-C30 score
From baseline to cycle 2 day 1 (up to approximately 1 month)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Secondary
Change From Baseline in EQ-5D-5L Health Utility Index
The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values.
All participants with non-missing score of EQ-5D-5L Health Utility Index (i.e. all five items were completed) at baseline
Posted
Mean
Standard Deviation
Change from baseline in EQ-5D score
From baseline up to cycle 2 day 1 (up to approximately 1 month)
ID
Title
Description
OG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
OG001
Conventional Care Regimens (CCRs)
Treatment options include best supportive care (BSC) only, azacitidine subcutaneous (SC) plus BSC, LDAC subcutaneous (SC) plus BSC, or IDAC intravenously (IV) plus BSC.
BSC only: Participants receive continuous 28-day cycles of best supportive care (BSC). BSC includes, but is not limited to, hydroxyurea for leukocytosis and/or differentiation syndrome associated with therapy of mutant isocitrate dehydrogenase (IDH) inhibition (ie, IDH differentiation syndrome), anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support.
AZA+BSC: Participants receive continuous 28-day cycles of azacitidine 775 mg/m2/day SC for 7 days, plus BSC.
LDAC+BSC: Participants receive continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC.
IDAC+BSC :Participants receive 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after intermediate-dose cytarabine (IDAC) therapy concludes per standard institutional practice.
Time Frame
Serious Adverse Events and Other (Not Including Serious) Adverse Events were collected form from first dose to study completion (approximately 78 months). All-Cause Mortality was assessed from randomization up to study completion (approximately 99 months).
Description
Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed/monitored for the treated population. All-Cause Mortality was assessed for the randomized population.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
AG-221
Participants receive continuous 28-day cycles of AG-221 100 mg orally (PO) once a day (QD) for 28 days, plus best supportive care (BSC).
144
158
139
157
154
157
EG001
BSC Only
continuous 28-day cycles of BSC
20
22
10
22
11
22
EG002
Azacitidine + BSC
continuous 28-day cycles of azacitidine 75 mg/m2/day SC for 7 days, plus BSC
56
69
38
58
52
58
EG003
LDAC + BSC
continuous 28-day cycles of cytarabine 20 mg SC BID for 10 days, plus BSC
34
37
27
33
30
33
EG004
IDAC + BSC
28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after IDAC therapy concludes per standard institutional practice.
25
33
17
28
24
28
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
AGRANULOCYTOSIS
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG0030 affected33 at risk
EG0040 affected28 at risk
ANAEMIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0007 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
FEBRILE BONE MARROW APLASIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
FEBRILE NEUTROPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG00033 affected157 at risk
EG0015 affected22 at risk
EG00214 affected58 at risk
EG003
HAEMORRHAGIC DISORDER
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HYPERLEUKOCYTOSIS
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
LEUKAEMOID REACTION
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LEUKOCYTOSIS
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LEUKOSTASIS SYNDROME
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
NEUTROPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PANCYTOPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
THROMBOCYTOPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG0006 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
ACUTE CORONARY SYNDROME
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ACUTE MYOCARDIAL INFARCTION
Cardiac disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
ANGINA PECTORIS
Cardiac disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ATRIAL FIBRILLATION
Cardiac disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ATRIAL FLUTTER
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BRADYCARDIA
Cardiac disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CARDIAC ARREST
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CARDIAC FAILURE
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CARDIAC FAILURE CONGESTIVE
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CARDIAC HYPERTROPHY
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CARDIOMYOPATHY
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CORONARY ARTERY DISEASE
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PERICARDIAL EFFUSION
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PERICARDITIS
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
SINUS BRADYCARDIA
Cardiac disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RETINAL HAEMORRHAGE
Eye disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ASCITES
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
COLITIS
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
CONSTIPATION
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CROHN'S DISEASE
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DIARRHOEA HAEMORRHAGIC
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ENTEROCOLITIS
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ENTEROCOLITIS HAEMORRHAGIC
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
GASTROINTESTINAL DISORDER
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
GASTROINTESTINAL HAEMORRHAGE
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
GINGIVAL HYPERTROPHY
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
INGUINAL HERNIA
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LOWER GASTROINTESTINAL HAEMORRHAGE
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
MELAENA
Gastrointestinal disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
MOUTH HAEMORRHAGE
Gastrointestinal disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
NAUSEA
Gastrointestinal disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ODYNOPHAGIA
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
OESOPHAGEAL ULCER
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
OESOPHAGITIS
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ORAL BLOOD BLISTER
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RECTAL HAEMORRHAGE
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
STOMATITIS
Gastrointestinal disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
UPPER GASTROINTESTINAL HAEMORRHAGE
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
VOMITING
Gastrointestinal disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ASTHENIA
General disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
FATIGUE
General disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
GENERAL PHYSICAL HEALTH DETERIORATION
General disorders
26.1
Systematic Assessment
EG00014 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
INFLUENZA LIKE ILLNESS
General disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
MALAISE
General disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
MUCOSAL INFLAMMATION
General disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
MULTIPLE ORGAN DYSFUNCTION SYNDROME
General disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0011 affected22 at risk
EG0021 affected58 at risk
EG003
ORGAN FAILURE
General disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
PHYSICAL DECONDITIONING
General disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PYREXIA
General disorders
26.1
Systematic Assessment
EG00015 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
CHOLANGITIS ACUTE
Hepatobiliary disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CHOLELITHIASIS MIGRATION
Hepatobiliary disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CHRONIC HEPATIC FAILURE
Hepatobiliary disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HEPATIC CYTOLYSIS
Hepatobiliary disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
HEPATIC FAILURE
Hepatobiliary disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HEPATOTOXICITY
Hepatobiliary disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HYPERBILIRUBINAEMIA
Hepatobiliary disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
GRAFT VERSUS HOST DISEASE
Immune system disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
ACARODERMATITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
ACUTE SINUSITIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ANAL ABSCESS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
APPENDICITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
BACTERAEMIA
Infections and infestations
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BREVIBACTERIUM INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BRONCHITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BRONCHOPULMONARY ASPERGILLOSIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
CAMPYLOBACTER INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CELLULITIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
CLOSTRIDIAL SEPSIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CLOSTRIDIUM DIFFICILE COLITIS
Infections and infestations
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
CLOSTRIDIUM DIFFICILE INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
COVID-19 PNEUMONIA
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DEVICE RELATED INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
DISSEMINATED MUCORMYCOSIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ENTEROCOCCAL INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ENTEROCOLITIS INFECTIOUS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
EPIGLOTTITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ESCHERICHIA BACTERAEMIA
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
ESCHERICHIA SEPSIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ESCHERICHIA URINARY TRACT INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
FURUNCLE
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
GASTROENTERITIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
GASTROINTESTINAL INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
GINGIVITIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HEPATIC INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HEPATOSPLENIC CANDIDIASIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HERPES SIMPLEX
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
INFLUENZA
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
INJECTION SITE CELLULITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
INTERVERTEBRAL DISCITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
KLEBSIELLA BACTERAEMIA
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LIVER ABSCESS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
LOCALISED INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
LOWER RESPIRATORY TRACT INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
MENINGITIS LISTERIA
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
NEUTROPENIC SEPSIS
Infections and infestations
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
NOCARDIA SEPSIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
NOCARDIOSIS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
OTITIS EXTERNA
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PERIORBITAL CELLULITIS
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PERIRECTAL ABSCESS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
PHARYNGITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PNEUMONIA
Infections and infestations
26.1
Systematic Assessment
EG00027 affected157 at risk
EG0012 affected22 at risk
EG0028 affected58 at risk
EG003
PNEUMONIA BACTERIAL
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PNEUMONIA FUNGAL
Infections and infestations
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
PNEUMONIA INFLUENZAL
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PNEUMONIA LEGIONELLA
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PNEUMONIA RESPIRATORY SYNCYTIAL VIRAL
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PSEUDOMONAS INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PYELONEPHRITIS ACUTE
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RESPIRATORY SYNCYTIAL VIRUS INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RESPIRATORY TRACT INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
SEPSIS
Infections and infestations
26.1
Systematic Assessment
EG00017 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
SEPTIC SHOCK
Infections and infestations
26.1
Systematic Assessment
EG0006 affected157 at risk
EG0012 affected22 at risk
EG0021 affected58 at risk
EG003
SINUSITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
SKIN INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
STAPHYLOCOCCAL BACTERAEMIA
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
STAPHYLOCOCCAL SEPSIS
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
STENOTROPHOMONAS INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
SUBCUTANEOUS ABSCESS
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
TOOTH ABSCESS
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
URETHRITIS
Infections and infestations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
URINARY TRACT INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
URINARY TRACT INFECTION ENTEROCOCCAL
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
VASCULAR DEVICE INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ANAPHYLACTIC TRANSFUSION REACTION
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ANKLE FRACTURE
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
FALL
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
FEMUR FRACTURE
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
INFUSION RELATED REACTION
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LOWER LIMB FRACTURE
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
OVERDOSE
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
POST PROCEDURAL HAEMORRHAGE
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
SUBDURAL HAEMATOMA
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
SUBDURAL HAEMORRHAGE
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
TRANSFUSION REACTION
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ALANINE AMINOTRANSFERASE INCREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BLAST CELL COUNT INCREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
BLOOD BILIRUBIN INCREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BLOOD CREATININE INCREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
EJECTION FRACTION DECREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
GENERAL PHYSICAL CONDITION ABNORMAL
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LIVER FUNCTION TEST INCREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PLATELET COUNT DECREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
TRANSAMINASES INCREASED
Investigations
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DECREASED APPETITE
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DEHYDRATION
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DIABETIC METABOLIC DECOMPENSATION
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HYPERGLYCAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HYPOKALAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HYPONATRAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
TUMOUR LYSIS SYNDROME
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ARTHRALGIA
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BACK PAIN
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BONE PAIN
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
JOINT EFFUSION
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
MUSCULAR WEAKNESS
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
NECK PAIN
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PAIN IN EXTREMITY
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
TENDONITIS
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ACUTE LEUKAEMIA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ACUTE LYMPHOCYTIC LEUKAEMIA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ACUTE MYELOID LEUKAEMIA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0006 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ACUTE MYELOID LEUKAEMIA RECURRENT
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DIFFERENTIATION SYNDROME
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0009 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ENDOMETRIAL CANCER
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
GASTRIC CANCER
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ONCOLOGIC COMPLICATION
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
SQUAMOUS CELL CARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
SQUAMOUS CELL CARCINOMA OF SKIN
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ATAXIA
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
BRAIN OEDEMA
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CEREBRAL HAEMORRHAGE
Nervous system disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CEREBRAL INFARCTION
Nervous system disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
DYSARTHRIA
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HAEMORRHAGE INTRACRANIAL
Nervous system disorders
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HEADACHE
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
INTRAVENTRICULAR HAEMORRHAGE
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ISCHAEMIC STROKE
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LOSS OF CONSCIOUSNESS
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
LUMBOSACRAL RADICULOPATHY
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
NORMAL PRESSURE HYDROCEPHALUS
Nervous system disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
SYNCOPE
Nervous system disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
CONFUSIONAL STATE
Psychiatric disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ACUTE KIDNEY INJURY
Renal and urinary disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
HAEMATURIA
Renal and urinary disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
OLIGURIA
Renal and urinary disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RENAL COLIC
Renal and urinary disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RENAL FAILURE
Renal and urinary disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
RENAL IMPAIRMENT
Renal and urinary disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
URINARY RETENTION
Renal and urinary disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
BENIGN PROSTATIC HYPERPLASIA
Reproductive system and breast disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
ACUTE RESPIRATORY FAILURE
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DYSPNOEA
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
EPISTAXIS
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
LUNG DISORDER
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0011 affected22 at risk
EG0021 affected58 at risk
EG003
LUNG INFILTRATION
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ORGANISING PNEUMONIA
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PLEURAL EFFUSION
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
PNEUMONITIS
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RESPIRATORY DISTRESS
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RESPIRATORY FAILURE
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ECCHYMOSIS
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PURPURA
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RASH
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
TOXIC SKIN ERUPTION
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HAEMORRHAGE
Vascular disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HYPOTENSION
Vascular disorders
26.1
Systematic Assessment
EG0006 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
ANAEMIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG00046 affected157 at risk
EG0012 affected22 at risk
EG0027 affected58 at risk
EG0037 affected33 at risk
EG0047 affected28 at risk
FEBRILE NEUTROPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG00014 affected157 at risk
EG0010 affected22 at risk
EG0027 affected58 at risk
EG003
LEUKOCYTOSIS
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG00020 affected157 at risk
EG0012 affected22 at risk
EG0023 affected58 at risk
EG003
LEUKOPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
NEUTROPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG00029 affected157 at risk
EG0012 affected22 at risk
EG00214 affected58 at risk
EG003
THROMBOCYTOPENIA
Blood and lymphatic system disorders
26.1
Systematic Assessment
EG00048 affected157 at risk
EG0012 affected22 at risk
EG00217 affected58 at risk
EG003
TACHYCARDIA
Cardiac disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0012 affected22 at risk
EG0021 affected58 at risk
EG003
CONJUNCTIVAL HAEMORRHAGE
Eye disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
DRY EYE
Eye disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0024 affected58 at risk
EG003
ABDOMINAL DISTENSION
Gastrointestinal disorders
26.1
Systematic Assessment
EG00010 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
ABDOMINAL PAIN
Gastrointestinal disorders
26.1
Systematic Assessment
EG00017 affected157 at risk
EG0010 affected22 at risk
EG0025 affected58 at risk
EG003
ABDOMINAL PAIN UPPER
Gastrointestinal disorders
26.1
Systematic Assessment
EG00011 affected157 at risk
EG0012 affected22 at risk
EG0024 affected58 at risk
EG003
CONSTIPATION
Gastrointestinal disorders
26.1
Systematic Assessment
EG00030 affected157 at risk
EG0012 affected22 at risk
EG00223 affected58 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
26.1
Systematic Assessment
EG00062 affected157 at risk
EG0010 affected22 at risk
EG00214 affected58 at risk
EG003
DRY MOUTH
Gastrointestinal disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
DYSPEPSIA
Gastrointestinal disorders
26.1
Systematic Assessment
EG0009 affected157 at risk
EG0011 affected22 at risk
EG0021 affected58 at risk
EG003
GINGIVAL BLEEDING
Gastrointestinal disorders
26.1
Systematic Assessment
EG00011 affected157 at risk
EG0011 affected22 at risk
EG0022 affected58 at risk
EG003
HAEMORRHOIDS
Gastrointestinal disorders
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0011 affected22 at risk
EG0025 affected58 at risk
EG003
MELAENA
Gastrointestinal disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
MOUTH HAEMORRHAGE
Gastrointestinal disorders
26.1
Systematic Assessment
EG00010 affected157 at risk
EG0011 affected22 at risk
EG0023 affected58 at risk
EG003
NAUSEA
Gastrointestinal disorders
26.1
Systematic Assessment
EG00069 affected157 at risk
EG0012 affected22 at risk
EG00216 affected58 at risk
EG003
STOMATITIS
Gastrointestinal disorders
26.1
Systematic Assessment
EG00015 affected157 at risk
EG0011 affected22 at risk
EG0024 affected58 at risk
EG003
VOMITING
Gastrointestinal disorders
26.1
Systematic Assessment
EG00040 affected157 at risk
EG0011 affected22 at risk
EG0029 affected58 at risk
EG003
ASTHENIA
General disorders
26.1
Systematic Assessment
EG00029 affected157 at risk
EG0012 affected22 at risk
EG00213 affected58 at risk
EG003
FATIGUE
General disorders
26.1
Systematic Assessment
EG00045 affected157 at risk
EG0010 affected22 at risk
EG00210 affected58 at risk
EG003
GENERAL PHYSICAL HEALTH DETERIORATION
General disorders
26.1
Systematic Assessment
EG00010 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
INFLUENZA LIKE ILLNESS
General disorders
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
INJECTION SITE PAIN
General disorders
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0026 affected58 at risk
EG003
NON-CARDIAC CHEST PAIN
General disorders
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0011 affected22 at risk
EG0023 affected58 at risk
EG003
OEDEMA PERIPHERAL
General disorders
26.1
Systematic Assessment
EG00033 affected157 at risk
EG0011 affected22 at risk
EG00213 affected58 at risk
EG003
PYREXIA
General disorders
26.1
Systematic Assessment
EG00037 affected157 at risk
EG0014 affected22 at risk
EG00214 affected58 at risk
EG003
HYPERBILIRUBINAEMIA
Hepatobiliary disorders
26.1
Systematic Assessment
EG00015 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
BRONCHITIS
Infections and infestations
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CELLULITIS
Infections and infestations
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0011 affected22 at risk
EG0022 affected58 at risk
EG003
INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
ORAL CANDIDIASIS
Infections and infestations
26.1
Systematic Assessment
EG00010 affected157 at risk
EG0011 affected22 at risk
EG0022 affected58 at risk
EG003
PHARYNGITIS
Infections and infestations
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
PNEUMONIA
Infections and infestations
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0011 affected22 at risk
EG0027 affected58 at risk
EG003
PNEUMONIA FUNGAL
Infections and infestations
26.1
Systematic Assessment
EG0003 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
RHINITIS
Infections and infestations
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
TOOTH INFECTION
Infections and infestations
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0010 affected22 at risk
EG0026 affected58 at risk
EG003
URINARY TRACT INFECTION
Infections and infestations
26.1
Systematic Assessment
EG00012 affected157 at risk
EG0012 affected22 at risk
EG0021 affected58 at risk
EG003
CONTUSION
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG00012 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
FALL
Injury, poisoning and procedural complications
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0010 affected22 at risk
EG0024 affected58 at risk
EG003
ALANINE AMINOTRANSFERASE INCREASED
Investigations
26.1
Systematic Assessment
EG0008 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
ASPARTATE AMINOTRANSFERASE INCREASED
Investigations
26.1
Systematic Assessment
EG0006 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
BLOOD ALKALINE PHOSPHATASE INCREASED
Investigations
26.1
Systematic Assessment
EG0005 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
BLOOD BILIRUBIN INCREASED
Investigations
26.1
Systematic Assessment
EG00041 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
BLOOD CREATININE INCREASED
Investigations
26.1
Systematic Assessment
EG00020 affected157 at risk
EG0010 affected22 at risk
EG0025 affected58 at risk
EG003
C-REACTIVE PROTEIN INCREASED
Investigations
26.1
Systematic Assessment
EG0008 affected157 at risk
EG0010 affected22 at risk
EG0024 affected58 at risk
EG003
ELECTROCARDIOGRAM QT PROLONGED
Investigations
26.1
Systematic Assessment
EG0008 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
WEIGHT DECREASED
Investigations
26.1
Systematic Assessment
EG00014 affected157 at risk
EG0010 affected22 at risk
EG0024 affected58 at risk
EG003
WEIGHT INCREASED
Investigations
26.1
Systematic Assessment
EG0000 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DECREASED APPETITE
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00049 affected157 at risk
EG0011 affected22 at risk
EG00213 affected58 at risk
EG003
HYPERGLYCAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00011 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
HYPERKALAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
HYPERURICAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00017 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
HYPOALBUMINAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0012 affected22 at risk
EG0024 affected58 at risk
EG003
HYPOCALCAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00015 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
HYPOKALAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00052 affected157 at risk
EG0011 affected22 at risk
EG00210 affected58 at risk
EG003
HYPOMAGNESAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00019 affected157 at risk
EG0011 affected22 at risk
EG0023 affected58 at risk
EG003
HYPONATRAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG00010 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
HYPOPHOSPHATAEMIA
Metabolism and nutrition disorders
26.1
Systematic Assessment
EG0009 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
ARTHRALGIA
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
BACK PAIN
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG00021 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
MUSCULAR WEAKNESS
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG00011 affected157 at risk
EG0011 affected22 at risk
EG0020 affected58 at risk
EG003
PAIN IN EXTREMITY
Musculoskeletal and connective tissue disorders
26.1
Systematic Assessment
EG00020 affected157 at risk
EG0010 affected22 at risk
EG0026 affected58 at risk
EG003
DIFFERENTIATION SYNDROME
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
26.1
Systematic Assessment
EG00016 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DIZZINESS
Nervous system disorders
26.1
Systematic Assessment
EG00023 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DYSGEUSIA
Nervous system disorders
26.1
Systematic Assessment
EG00012 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
HEADACHE
Nervous system disorders
26.1
Systematic Assessment
EG00024 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
PERIPHERAL SENSORY NEUROPATHY
Nervous system disorders
26.1
Systematic Assessment
EG0004 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
ANXIETY
Psychiatric disorders
26.1
Systematic Assessment
EG0009 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
CONFUSIONAL STATE
Psychiatric disorders
26.1
Systematic Assessment
EG0009 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
DEPRESSION
Psychiatric disorders
26.1
Systematic Assessment
EG0008 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
INSOMNIA
Psychiatric disorders
26.1
Systematic Assessment
EG00024 affected157 at risk
EG0011 affected22 at risk
EG00210 affected58 at risk
EG003
CHRONIC KIDNEY DISEASE
Renal and urinary disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
DYSURIA
Renal and urinary disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0010 affected22 at risk
EG0023 affected58 at risk
EG003
VAGINAL HAEMORRHAGE
Reproductive system and breast disorders
26.1
Systematic Assessment
EG0001 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
COUGH
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG00027 affected157 at risk
EG0013 affected22 at risk
EG0029 affected58 at risk
EG003
DYSPNOEA
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG00034 affected157 at risk
EG0012 affected22 at risk
EG0023 affected58 at risk
EG003
EPISTAXIS
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG00027 affected157 at risk
EG0013 affected22 at risk
EG00210 affected58 at risk
EG003
OROPHARYNGEAL PAIN
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0008 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
PLEURAL EFFUSION
Respiratory, thoracic and mediastinal disorders
26.1
Systematic Assessment
EG0008 affected157 at risk
EG0011 affected22 at risk
EG0023 affected58 at risk
EG003
ERYTHEMA
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG0006 affected157 at risk
EG0010 affected22 at risk
EG0025 affected58 at risk
EG003
PETECHIAE
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0010 affected22 at risk
EG0024 affected58 at risk
EG003
PRURITUS
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG00013 affected157 at risk
EG0010 affected22 at risk
EG0020 affected58 at risk
EG003
RASH
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG00011 affected157 at risk
EG0010 affected22 at risk
EG0026 affected58 at risk
EG003
RASH MACULO-PAPULAR
Skin and subcutaneous tissue disorders
26.1
Systematic Assessment
EG0009 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
HAEMATOMA
Vascular disorders
26.1
Systematic Assessment
EG00011 affected157 at risk
EG0010 affected22 at risk
EG0022 affected58 at risk
EG003
HYPERTENSION
Vascular disorders
26.1
Systematic Assessment
EG0008 affected157 at risk
EG0010 affected22 at risk
EG0024 affected58 at risk
EG003
HYPOTENSION
Vascular disorders
26.1
Systematic Assessment
EG00015 affected157 at risk
EG0010 affected22 at risk
EG0021 affected58 at risk
EG003
PHLEBITIS
Vascular disorders
26.1
Systematic Assessment
EG0002 affected157 at risk
EG0011 affected22 at risk
EG0023 affected58 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
p-value from a Cochran-Mantel-Haenszel test comparing the response rates between the AG-221 group and the combined CCR group with stratification factors of prior intensive therapy for AML and primary refractory status
Odds Ratio (OR)
6.08
2-Sided
95
3.32
11.14
Odds ratio from logistic regression
Superiority
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG0004.9(3.7 to 5.9)
OG0012.6(1.9 to 4.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Stratified Log Rank
0.0200
Hazard Ratio (HR)
0.72
2-Sided
95
0.55
0.95
The hazard ratio is from a Cox proportional hazards model stratified by prior intensive therapy for AML and primary refractory status.
Superiority
Units
Counts
Participants
OG00064
OG00116
Title
Denominators
Categories
Title
Measurements
OG0007.4(5.6 to 12.7)
OG00133.3(2.5 to NA)Not Estimable due to only 6 participants acheiving CR/CRi/CRp/PR/MLFS. For KM methodology to produce an ULN, need 50% of participants to acheive CR/CRi/CRp/PR/MLFS.
Units
Counts
Participants
OG00025
OG0017
Title
Denominators
Categories
Title
Measurements
OG00058.0(23 to 242)
OG00156.0(27 to 63)
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG00010
OG00113
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG00027
OG00130
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG0000.379(0.303 to 0.454)
OG0010.263(0.193 to 0.337)
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG00047
OG00110
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Fisher Exact
<0.0001
Superiority
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG00037
OG0016
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Fisher Exact
<0.0001
Superiority
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG00067
OG00118
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Fisher Exact
<0.0001
Superiority
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG0007
OG0012
Units
Counts
Participants
OG000158
OG001161
Title
Denominators
Categories
Title
Measurements
OG0004.9(4.0 to 6.0)
OG0011.9(1.4 to 2.5)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Stratified Log Rank
<0.0001
Hazard Ratio (HR)
0.53
2-Sided
95
0.41
0.67
The hazard ratio was from a Cox proportional hazards model stratified by prior intensive therapy for AML and primary refractory status
Superiority
Units
Counts
Participants
OG000157
OG001141
Title
Denominators
Categories
Treatment-Emergent Adverse Event (TEAE)
Title
Measurements
OG000157
OG001131
TEAE Related to Study Drug
Title
Measurements
OG000122
OG00186
Grade ≥ 3 TEAE
Title
Measurements
OG000148
OG001112
Grade ≥ 3 TEAE Related to Study Drug
Title
Measurements
OG00075
OG00149
Serious TEAE
Title
Measurements
OG000139
OG00192
Serious TEAE Related to Study Drug
Title
Measurements
OG00034
OG00130
TEAE Leading to Discontinuation of Study Drug
Title
Measurements
OG00038
OG00116
Treatment-related TEAE Leading to Discontinuation of Study Drug
Title
Measurements
OG0005
OG0016
TEAE Leading to Study Drug Dose Reduction Only
Title
Measurements
OG00022
OG0013
Treatment-related TEAE Leading to Study Drug Dose Reduction Only
Title
Measurements
OG00018
OG0013
TEAE Leading to Study Drug Dose Interruption Only
Title
Measurements
OG00085
OG00136
Treatment-related TEAE Leading to Study Drug Dose Interruption Only
Title
Measurements
OG00046
OG00121
TEAE Leading to Study Drug Dose Reduction or Dose Interruption
Title
Measurements
OG00092
OG00137
Treatment-related TEAE Leading to Study Drug Dose Reduction or Dose Interruption