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The purpose of the study is to determine the maximal tolerated dose and schedule of CC-486, known as oral azacitidine, in patients with AML or MDS after allogeneic hematopoetic stem cell transplant (HSCT). HSCT is more frequently used in AML or MDS as a potential curative therapy. However, disease recurrence/relapse and graft-versus-host disease (GVHD) remain the principal causes of fatal complications after transplantation. Oral azacitidine has significant activity in MDS and AML. Oral azacitidine has also demonstrated immunomodulatory activity in AML patients after allogeneic HSCT. An oral formulation of oral azacitidine provides a convenient route of administration and an opportunity to deliver the drug over a prolonged schedule.
This is an open-label, multicenter study of oral azacitidine in MDS or AML patients who have undergone allogeneic HSCT. The study consists of three phases: Screening, Treatment and Follow-up. During the Screening phase, the study doctor will do tests to see if the patient is suitable for this study. The patients meeting protocol-specified entry criteria will enter the treatment phase and be assigned to receive one of the oral azacitidine cohorts. The dosing group of 200 mg QD on Days 1 to 7 will be evaluated first (ie, Cohort 1). In the event that unacceptable toxicity occurs in Cohort 1, then oral azacitidine may be evaluated at lower dose levels (eg, 150 mg). If the dosing regimen is confirmed to be safe in Cohort 1, other cohorts will be evaluated sequentially. During the treatment phase, patients will be monitored closely for safety and tolerability. Dosing interruption or delay, dose or schedule reduction, intra-subject dose/schedule escalation or re-escalation may occur on the basis of protocol-specified dosing adjustment guidelines. Safety will be monitored throughout the study at predetermined intervals and as clinically indicated by vital signs, physical examination, performance status, laboratory tests and evaluation of adverse events. The patient can continue to receive the study treatment for up to 12 months provided that they benefit from the study treatment and all protocol-specified criteria are met. However, the patient may receive the study treatment for less than 12 months due to adverse event, disease recurrence or progression. When the study treatment is discontinued, all patients who have received at least one dose of oral azacitidine will be asked to see the study doctor for the treatment discontinuation visit. Thereafter, all patients discontinued from the study treatment will enter the Follow-up phase for safety and survival follow up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CC-486 | Experimental | Dose of 150 mg, 200 mg, or 300 mg once daily (QD) for the first 7, 10, or 14 days of each 28-day cycle, starting 42-84 days after transplantation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CC-486 | Drug | Cohorts of 3 to 6 subjects will be treated at escalating or de-escalating sequential dose levels until a preliminary Maximum Tolerated Dose (MTD) is identified. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Participants With Dose Limiting Toxicities (DLT) | A DLT included events that started within 28 days of the first dose of CC-486 in a 28-day cycle, constituted a change from baseline irrespective of outcome, as decided by the investigator to be related to CC-486 including:
The maximum tolerated dose is defined as the cohort delivering the highest dose in which no more than 33% of the evaluable subjects had a DLT The safety population included subjects who received ≥ 1 dose of CC-486 | 2 months (Cycles 1 and 2) |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | A TEAE was defined as any AE with an onset date on or after the first dose of IP or any event already present that worsened in severity or increased in frequency after exposure to IP up to 28 days after the last dose. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.0, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above. | From the first dose of investigational product (IP) up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall; up to the final data cut off date of 14 July 2017 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Graft Versus Host Disease During the Entire Course of the Study | Acute graft versus host disease generally occurs after allogeneic hematopoietic stem cell transplantation. It is a reaction of donor immune cells against host tissues. The 3 main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract. Chronic GVHD is scored per the National Institute of Health consensus conference grading system. Clinical manifestations of chronic GVHD include skin involvement resembling lichen planus or the cutaneous manifestations of scleroderma; dry oral mucosa with ulcerations and sclerosis of the gastrointestinal tract; and a rising serum bilirubin concentration. |
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Inclusion Criteria:
At the time of allogeneic HSCT:
Be able to start study drug between 42 to 84 days following allogeneic HSCT
Post transplant bone marrow blast count ≤ 5% confirmed within 21 days prior to starting study therapy
Adequate engraftment within 14 days prior to starting study therapy:
Adequate organ function:
Adequate coagulation (Prothrombin time [PT] ≤ 15 seconds, Partial thromboplastin time (PTT) ≤ 40 seconds, and/or International normalized ratio [INR] ≤ 1.5)
Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL at screening).
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Must agree to follow protocol-specified pregnancy precautions
Exclusion Criteria:
Use of any of the following after transplantation and prior to starting oral azacitidine:
Active Graft-versus-host disease (GVHD) grade II or higher
Any evidence of gastrointestinal (GI) GVHD
Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg
Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)
Active uncontrolled systemic fungal, bacterial or viral infection
Presence of malignancies, other than MDS or AML, within the previous 12 months
Significant active cardiac disease within the previous 6 months
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| Name | Affiliation | Role |
|---|---|---|
| Barry Skikne, M.D., FACP; FCP (SA) | Celgene Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan-Kettering Cancer Center. | New York | New York | 10065 | United States | ||
| University Hospitals Cleveland Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29933073 | Derived | de Lima M, Oran B, Champlin RE, Papadopoulos EB, Giralt SA, Scott BL, William BM, Hetzer J, Laille E, Hubbell B, Skikne BS, Craddock C. CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes. Biol Blood Marrow Transplant. 2018 Oct;24(10):2017-2024. doi: 10.1016/j.bbmt.2018.06.016. Epub 2018 Jun 20. |
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Participants with a confirmed diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received an allogeneic hematopoietic stem cell transplant (HSCT) were eligible to participate and begin study drug between 42 and 84 days post HSCT. One participant was enrolled into the study but discontinued before being treated.
The multicenter study was conducted in the United States and the United Kingdom. Participants were enrolled at 5 study sites.
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| ID | Title | Description |
|---|---|---|
| FG000 | CC-486 200 mg Days 1-7 (Cohort 1) | Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
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| From the first dose of CC-486 up to study discontinuation or death. Up to final data cut off date of 14 July 2017; up to 186 weeks and 4 days |
| Kaplan Meier Estimate of Time to Discontinuation From Treatment | The time to discontinuation from treatment was assessed as an estimate of treatment tolerability and was defined as the interval from the date of the first IP dose to the date of discontinuation from IP as indicated on the discontinuation from treatment Case Report Form page. Time to discontinuation from study treatment was analyzed using the Kaplan-Meier method where participants who did not discontinue were censored at the date of last visit. | From the first dose of IP dose to the date of discontinuation from IP; the overall median time to discontinuation of IP was 283.5 days |
| Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t) | Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. | On Day 1, pharmacokinetic (PK) samples were collected at predose and over a 6-hour period following drug administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose; Cycle 1 or 2 until 6 hours after CC-486 administration. |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated to Infinity (AUC-inf; AUC0-∞) Of CC-486 | Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported. | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
| Maximum Observed Concentration (Cmax) Of CC-486 | Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
| Time to Reach Maximum Concentration (Tmax) of CC-486 | Time to Cmax, obtained directly from the observed concentration versus time data. | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
| Terminal Half-Life (T1/2) of CC-486 | Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 will only be calculated when a reliable estimate for λz can be obtained. | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
| Apparent Total Clearance (CL/F) of CC-486 | Apparent total clearance, calculated as [Dose/AUCinf]. | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
| Apparent Volume of Distribution (Vz/F) of CC-486 | Apparent volume of distribution, calculated as [(CL/F)/λz].Apparent volume of distribution, calculated as [(CL/F)/λz]. | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
| Percentage of Participants With Disease Relapse or Progression | Disease relapse was defined as the reappearance of > 5% blasts in the bone marrow that persists for at least 4 weeks. Disease progression was defined as the reappearance of > 10% of blasts in the bone marrow that persisted for at least 4 weeks. | Date of first dose of IP to disease relapse or progression; up to data cut-off date of 14 July 2017; median number of days assessed was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3. |
| Time to Disease Recurrence/Progression | Time to disease relapse/progression was defined as the interval from the date of allogeneic HSCT to the date of treatment discontinuation or study discontinuation where reason for discontinuation is disease relapse or disease progression, or the date of disease progression recorded on the survival electronic Case Report Form page, whichever occurred first. Time to disease relapse/progression was analyzed using competing risk methods where death without documented relapse/progression was treated as a competing risk for relapse/progression. relapse/progression. | Date of allogenic HSCT to disease progression or relaopse; up to data cut-off date of 14 July 2017; median number of days assessed was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3. |
| Overall Survival | Overall Survival was defined as the time from the date of allogeneic hematopoietic stem cell transplantation to death from any cause. | Date of the allogeneic HSCT to death from any cause. Median number of days participants were assessed from first dose to last contact was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3. |
| Kaplan Meier Estimate of Relapse-Free Survival (RFS) | Relapse-free survival was defined as the interval from the date of allogeneic HSCT to the date of first documented > 5% blasts in the bone marrow or death from any cause, whichever occurs first. Participants who were still alive and continued to have less than or equal to 5% blasts in the bone marrow or who were lost to follow-up were censored at the date of their last response assessment. | Date of allogenic HSCT to date of progression or death from any cause; Median number of days participants were assessed from first dose to last contact was 963 days for Cohort 1, 674.8 days for Cohort 2, 577.5 days for Cohort 3A and 553 days for Cohort 3 |
| Cleveland |
| Ohio |
| 44106 |
| United States |
| MD Anderson Cancer Center The University of Texas | Houston | Texas | 77030 | United States |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109-4417 | United States |
| Queen Elizabeth Hospital UHB NHS Foundation Trust | Birmingham | B15 2TH | United Kingdom |
| FG001 | CC-486 300 mg Days 1-7 (Cohort 2) | Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| FG002 | CC-486 150 mg Days 1-14 (Cohort 3A) | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| FG003 | CC-486 200 mg Days 1-14 (Cohort 3) | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
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| COMPLETED | Completed entire study treatment |
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| NOT COMPLETED |
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The safety population includes all participants who received at least 1 dose of investigational product (IP)
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| ID | Title | Description |
|---|---|---|
| BG000 | CC-486 200 mg Days 1-7 (Cohort 1) | Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death |
| BG001 | CC-486 300 mg Days 1-7 (Cohort 2) | Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| BG002 | CC-486 150 mg Days 1-14 (Cohort 3A) | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| BG003 | CC-486 200 mg Days 1-14 (Cohort 3) | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Diagnosis at Study Entry | The number of participants with a diagnosis of AML or MDS | Count of Participants | Participants |
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| MDS International Prognostic Scoring System (IPSS) Risk Classification | The MDS IPSS score assesses the severity of MDS based on 3 prognostic factors each assigned a score: the percentage of bone marrow blasts, chromosome changes in the marrow cells (karyotype) and the presence of one or more low blood cell counts (cytopenias). The IPSS score is the sum of the bone marrow blast + karyotype + cytopenia score and ranges from 0 (low risk) to 3.5 (high risk). Prognosis is categorized as Low risk (score = 0), Intermediate-1 (score 0.5 to 1.0), Intermediate-2 (score 1.5 to 2.0) or High risk (score ≥ 2.5). | MDS Participants Have This Classification | Count of Participants | Participants |
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| Eastern Cooperative Oncology Group (ECOG) Performance Status | ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity) | Count of Participants | Participants |
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| Time from MDS or AML Diagnosis to Allogeneic HSCT | Mean | Standard Deviation | months |
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| AML World Health Organization (WHO) Classification | Description:AML is classified using the WHO classification system based upon a combination of morphology, immunophenotype, genetics, and clinical features. There are several broad groups and include: 1. AML with genetic abnormalities; 2. AML with multilineage dysplasia 3. AML related to previous chemotherapy or radiation 4. Unspecified AML - do not fall into the above groups | Number | Participants:Participants |
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| Age, Categorical | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||
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| Primary | The Number of Participants With Dose Limiting Toxicities (DLT) | A DLT included events that started within 28 days of the first dose of CC-486 in a 28-day cycle, constituted a change from baseline irrespective of outcome, as decided by the investigator to be related to CC-486 including:
The maximum tolerated dose is defined as the cohort delivering the highest dose in which no more than 33% of the evaluable subjects had a DLT The safety population included subjects who received ≥ 1 dose of CC-486 | The safety population included all participants who received at least one dose of investigational product. | Posted | Number | participants | 2 months (Cycles 1 and 2) |
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| Primary | Number of Participants With Treatment Emergent Adverse Events (TEAE) | A TEAE was defined as any AE with an onset date on or after the first dose of IP or any event already present that worsened in severity or increased in frequency after exposure to IP up to 28 days after the last dose. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.0, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above. | The safety population includes all participants who received at least one dose of IP. | Posted | Number | participants | From the first dose of investigational product (IP) up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall; up to the final data cut off date of 14 July 2017 |
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| Secondary | Percentage of Participants With Graft Versus Host Disease During the Entire Course of the Study | Acute graft versus host disease generally occurs after allogeneic hematopoietic stem cell transplantation. It is a reaction of donor immune cells against host tissues. The 3 main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract. Chronic GVHD is scored per the National Institute of Health consensus conference grading system. Clinical manifestations of chronic GVHD include skin involvement resembling lichen planus or the cutaneous manifestations of scleroderma; dry oral mucosa with ulcerations and sclerosis of the gastrointestinal tract; and a rising serum bilirubin concentration. | Safety population includes all participants who received at least 1 dose of IP. | Posted | Number | 95% Confidence Interval | percentage of participants | From the first dose of CC-486 up to study discontinuation or death. Up to final data cut off date of 14 July 2017; up to 186 weeks and 4 days |
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| Secondary | Kaplan Meier Estimate of Time to Discontinuation From Treatment | The time to discontinuation from treatment was assessed as an estimate of treatment tolerability and was defined as the interval from the date of the first IP dose to the date of discontinuation from IP as indicated on the discontinuation from treatment Case Report Form page. Time to discontinuation from study treatment was analyzed using the Kaplan-Meier method where participants who did not discontinue were censored at the date of last visit. | The safety population includes all participants who received at least one dose of investigational product. Participants who were on treatment at the time of study closure were censored at the date of last available visit | Posted | Median | Inter-Quartile Range | Days | From the first dose of IP dose to the date of discontinuation from IP; the overall median time to discontinuation of IP was 283.5 days |
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| Secondary | Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of CC-486 (AUC-t) | Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. | The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is <1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | On Day 1, pharmacokinetic (PK) samples were collected at predose and over a 6-hour period following drug administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose; Cycle 1 or 2 until 6 hours after CC-486 administration. |
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| Secondary | Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated to Infinity (AUC-inf; AUC0-∞) Of CC-486 | Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported. | The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is <1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
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| Secondary | Maximum Observed Concentration (Cmax) Of CC-486 | Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. | The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is <1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
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| Secondary | Time to Reach Maximum Concentration (Tmax) of CC-486 | Time to Cmax, obtained directly from the observed concentration versus time data. | The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is <1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined. | Posted | Median | Full Range | hours | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
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| Secondary | Terminal Half-Life (T1/2) of CC-486 | Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 will only be calculated when a reliable estimate for λz can be obtained. | The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is <1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
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| Secondary | Apparent Total Clearance (CL/F) of CC-486 | Apparent total clearance, calculated as [Dose/AUCinf]. | The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is <1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
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| Secondary | Apparent Volume of Distribution (Vz/F) of CC-486 | Apparent volume of distribution, calculated as [(CL/F)/λz].Apparent volume of distribution, calculated as [(CL/F)/λz]. | The PK population were those with evaluable CC-486 plasma PK profiles; PK data from those who received CC-486 200 mg QD were combined because following a single CC-486 dose, the half-life elimination is <1 h; CC 486 does not accumulate following multiple administrations. CC-486 200 mg Days 1-7 and CC-486 200 mg Days 1-14 arms can be combined. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | On Day 1, PK samples were collected at predose and over the 6-hour period following CC-486 administration on the following schedule: 0.5, 1, 1.5, 2, 2.5, 3, 4, and 6 hours post-dose at Cycle 1 or 2 until 6 hours after CC-486 administration. |
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| Secondary | Percentage of Participants With Disease Relapse or Progression | Disease relapse was defined as the reappearance of > 5% blasts in the bone marrow that persists for at least 4 weeks. Disease progression was defined as the reappearance of > 10% of blasts in the bone marrow that persisted for at least 4 weeks. | Preliminary efficacy population included all participants who received at ≥ 1 dose of IP and had at ≥ 1 post-baseline efficacy assessment performed. | Posted | Number | Percentage of Participants | Date of first dose of IP to disease relapse or progression; up to data cut-off date of 14 July 2017; median number of days assessed was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3. |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Time to Disease Recurrence/Progression | Time to disease relapse/progression was defined as the interval from the date of allogeneic HSCT to the date of treatment discontinuation or study discontinuation where reason for discontinuation is disease relapse or disease progression, or the date of disease progression recorded on the survival electronic Case Report Form page, whichever occurred first. Time to disease relapse/progression was analyzed using competing risk methods where death without documented relapse/progression was treated as a competing risk for relapse/progression. relapse/progression. | Preliminary efficacy population included all participants who received at ≥ 1 dose of IP and had at ≥ 1 post-baseline efficacy assessment performed. Participants who were lost to follow-up without documented relapse/progression, or were alive at last follow-up without documented relapse/progression were censored at the date of the last assessment. | Posted | Mean | Standard Deviation | days | Date of allogenic HSCT to disease progression or relaopse; up to data cut-off date of 14 July 2017; median number of days assessed was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3. |
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| Secondary | Overall Survival | Overall Survival was defined as the time from the date of allogeneic hematopoietic stem cell transplantation to death from any cause. | Preliminary efficacy population includes all participants who received at least 1 dose of IP and had at least 1 post-baseline efficacy assessment performed. All participants were followed until drop-out, death, or study closure. Participants who dropped out or were alive at study closure were censored at the time of last contact, as appropriate. | Posted | Median | Inter-Quartile Range | Days | Date of the allogeneic HSCT to death from any cause. Median number of days participants were assessed from first dose to last contact was 963.0 days for Cohort 1, 743.5 days for Cohort 2, 675.5 days for Cohort 3A and 559.0 days for Cohort 3. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Kaplan Meier Estimate of Relapse-Free Survival (RFS) | Relapse-free survival was defined as the interval from the date of allogeneic HSCT to the date of first documented > 5% blasts in the bone marrow or death from any cause, whichever occurs first. Participants who were still alive and continued to have less than or equal to 5% blasts in the bone marrow or who were lost to follow-up were censored at the date of their last response assessment. | Preliminary efficacy population includes all participants who received at least 1 dose of IP and had at least 1 post-baseline efficacy assessment performed. Participants who were still alive and continued to have ≤5% blasts in the bone marrow or who were lost to follow-up were censored at the date of their last response assessment. | Posted | Median | Inter-Quartile Range | Days | Date of allogenic HSCT to date of progression or death from any cause; Median number of days participants were assessed from first dose to last contact was 963 days for Cohort 1, 674.8 days for Cohort 2, 577.5 days for Cohort 3A and 553 days for Cohort 3 |
|
From the first dose of IP up to 28 days after the last dose of IP. The median duration of exposure was 252.5 days overall.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CC-486 200 mg Days 1-7 (Cohort 1) | Participants received CC-486 200 mg by mouth (PO) once daily (QD) on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event (AE), disease recurrence or relapse, progressive disease (PD), development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death | 2 | 3 | 1 | 3 | 3 | 3 |
| EG001 | CC-486 300 mg Days 1-7 (Cohort 2) | Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. | 4 | 4 | 3 | 4 | 4 | 4 |
| EG002 | CC-486 150 mg Days 1-14 (Cohort 3A) | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. | 2 | 4 | 2 | 4 | 4 | 4 |
| EG003 | CC-486 200 mg Days 1-14 (Cohort 3) | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. | 11 | 19 | 6 | 19 | 18 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemolysis | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Graft versus host disease in gastrointestinal tract | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Pneumonia respiratory syncytial viral | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Vertigo positional | Ear and labyrinth disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Keratitis | Eye disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Photophobia | Eye disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Chronic graft versus host disease in skin | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Graft versus host disease | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Graft versus host disease in gastrointestinal tract | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Graft versus host disease in liver | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Graft versus host disease in skin | Immune system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Bacterial infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Catheter site cellulitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Corneal infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Nail infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Pneumonia respiratory syncytial viral | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Skin candida | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Radial nerve palsy | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Bladder spasm | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Obliterative bronchiolitis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Rosacea | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
|
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission up to 90 additional days. Investigator must delete confidential data before submission or defer publication to permit patent applications.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anne McClain, Senior Manager | Celgene Corporation | 888-260-1599 | ClinicalTrialDisclosure@Celgene.com |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000709231 | cc-486 |
Not provided
Not provided
Not provided
|
|
|
| White |
|
|
| Not Collected or Reported |
|
|
|
| Myelodysplastic Syndromes |
|
|
|
|
|
|
| AML With Myelodysplasia Related Changes |
|
|
| Therapy related Myeloid Neoplasms |
|
|
| AML Not Otherwise Specified |
|
|
|
| OG001 | CC-486 300 mg Days 1-7 | Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG003 | CC-486 200 mg Days 1-14 | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG003 | CC-486 200 mg Days 1-14 | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced, adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG003 | CC-486 200 mg Days 1-14 | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced, adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death.
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
|
|
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
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| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
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| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG003 | CC-486 200 mg Days 1-14 (Cohort 3) | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced, adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
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| OG001 | CC-486 300 mg Days 1-7 | Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG003 | CC-486 200 mg Days 1-14 | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced, adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
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| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG003 | CC-486 200 mg Days 1-14 | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced, adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
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Participants received CC-486 300 mg by mouth once daily on Days 1 to 7 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG002 | CC-486 150 mg Days 1-14 | Participants received CC-486 150 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced an adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease, withdrawal of consent, lost to follow-up, protocol violation or death. |
| OG003 | CC-486 200 mg Days 1-14 | Participants received CC-486 200 mg by mouth once daily on Days 1 to 14 of each 28-day cycle for a maximum duration of 12 months or until they experienced, adverse event, disease recurrence or relapse, progressive disease, development of Grade III/IV acute graft versus host disease (GVHD), withdrawal of consent, lost to follow-up, protocol violation or death. |
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