Safety and Efficacy of Melflufen and Dexamethasone in Relapsed and/or Relapsed-Refractory Multiple Myeloma Patients
Official Title
An Open-Label Phase I/IIa Study of the Safety and Efficacy of Melphalan-flufenamide (Melflufen) and Dexamethasone Combination for Patients With Relapsed and/or Relapsed-Refractory Multiple Myeloma
Acronym
Not provided
Organization
Oncopeptides ABINDUSTRY
Status Module
Record Verification Date
Oct 2020
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The study was terminated at median 46-48 months long term follow-up and mature overall survival follow-up data.
Expanded Access Info
No
Start Date
Jul 2013Actual
Primary Completion Date
Dec 2017Actual
Completion Date
Mar 2020Actual
First Submitted Date
Jul 9, 2013
First Submission Date that Met QC Criteria
Jul 11, 2013
First Posted Date
Jul 12, 2013Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 29, 2020
Results First Submitted that Met QC Criteria
Aug 7, 2020
Results First Posted Date
Aug 24, 2020Actual
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
Oct 22, 2020
Last Update Posted Date
Oct 23, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Oncopeptides ABINDUSTRY
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
The study will explore escalating doses of melflufen in combination with dexamethasone in small groups of patients to find the maximum tolerated dose of melflufen. That dose will then be used to determine the efficacy and safety profile of melflufen in combination with dexamethasone in a larger group of patients.
Intravenous (IV) infusion of 15 milligram (mg) melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Drug: Melflufen
Drug: Dexamethasone
Phase I: Melflufen 25 mg + Dexamethasone
Experimental
IV infusion of 25 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Drug: Melflufen
Drug: Dexamethasone
Phase I: Melflufen 40 mg + Dexamethasone
Experimental
IV infusion of 40 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Drug: Melflufen
Drug: Dexamethasone
Phase I: Melflufen 55 mg + Dexamethasone
Experimental
IV infusion of 55 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Drug: Melflufen
Drug: Dexamethasone
Phase I + II: Melflufen 40 mg + Dexamethasone
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Melflufen
Drug
Phase I + II: Melflufen 40 mg + Dexamethasone
Phase I: Melflufen 15 mg + Dexamethasone
Phase I: Melflufen 25 mg + Dexamethasone
Phase I: Melflufen 40 mg + Dexamethasone
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Patients Who Achieved Best Overall Disease Response
The best overall disease response on treatment including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) or progressive disease (PD) were evaluated. Starting on completion of Cycle 2, response was assessed according to International Myeloma Working Group (IMWG) criteria based on Investigator's assessment for all patients at every cycle during treatment period. PD was defined as increase of ≥25% from lowest response value in any 1 of the following: serum M-component (absolute increase must be ≥0.5 gram/deciliter) and/or urine M-component (absolute increase must be ≥200 mg/24 hr); development of new bone lesions or soft tissue plasmacytomas or increase in size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that could be attributed solely to plasma cell proliferative disorder. SD was defined as not meeting criteria for CR, VGPR, PR or PD.
Baseline (Cycle 1 Day 1) and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Overall Response Rate (ORR)
ORR was defined as percentage of patients with an overall response (OR), defined as first occurrence of confirmed disease response including PR or better (i.e, PR, VGPR, CR or sCR). Starting on completion of Cycle 2, response was assessed according to IMWG criteria based on Investigator's assessment for all patients at every cycle during treatment period. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum plus urine M-protein level <100 mg/24hr and >90% decrease in difference between involved and uninvolved free light chain (FLC) levels (only in FLC diseased patients). CR was defined as negative immunofixation on serum and urine, loss of any soft tissue plasmacytomas, <5% plasma cells in bone marrow and normal FLC ratio of 0.26 to 1.65 (only in FLC diseased patients). sCR was defined as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or 2 to 4 color flow cytometry.
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Secondary Outcomes
Measure
Description
Time Frame
Duration of Disease Response (DOR)
The DOR to treatment was defined as time from first response (PR or better) to disease progression or death, or date of last evaluable disease response assessment for those who had not progressed or died. DOR was estimated using Kaplan-Meier statistics.
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female, age 18 years or older
Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease
Patient has measurable disease defined as any of the following:
Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis
≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
If no monoclonal protein is detected, then ≥ 30% monoclonal bone marrow plasma cells
Patient has had at least 2 or more prior lines of therapy including lenalidomide and bortezomib and has demonstrated disease progression on or within 60 days of completion of the last therapy
Life expectancy of ≥6 months
Patient has an ECOG performance status ≤ 2 (Patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible)
Females of childbearing potential must have a negative serum or urine pregnancy test prior to patient registration
Female patients of child bearing potential and non-vasectomized male patients agree to practice appropriate methods of birth control
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
The patient has, or accepts to have, an acceptable infusion device for infusion of melflufen
12 lead ECG with QtcF interval ≤ 470 msec
The following laboratory results must be met within 21 days of patient registration:
Absolute neutrophil count ≥ 1,000 cells/dL (1.0 x 109/L)
Patient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participation in this study
Known active infection requiring parenteral or oral anti-infective treatment
Other malignancy within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix
Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to patient registration.
Pregnant or breast-feeding females
Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
Known HIV or hepatitis B or C viral infection
Patient has concurrent symptomatic amyloidosis or plasma cell leukemia
POEMS syndrome
Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to start of study treatment. Biologic, novel therapy (including investigational agents in this class) or corticosteroids within 2 weeks prior to patient registration. Patient has side effects of the previous therapy > grade 1 or previous baseline.
Prior peripheral stem cell transplant within 12 weeks of patient registration
Radiotherapy within 21 days prior to Cycle 1 Day 1. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
Richardson PG, Bringhen S, Voorhees P, Plesner T, Mellqvist UH, Reeves B, Paba-Prada C, Zubair H, Byrne C, Chauhan D, Anderson K, Nordstrom E, Harmenberg J, Palumbo A, Sonneveld P. Melflufen plus dexamethasone in relapsed and refractory multiple myeloma (O-12-M1): a multicentre, international, open-label, phase 1-2 study. Lancet Haematol. 2020 May;7(5):e395-e407. doi: 10.1016/S2352-3026(20)30044-2. Epub 2020 Mar 23.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
The study was conducted in 2 parts: Phase I (dose escalation) and Phase II (maximum tolerated dose [MTD]). During Phase I, the standard 3 + 3 design was followed with 3 to 6 patients tested at each dose level, depending on the dose limiting toxicity (DLT) observed. During Phase II, patients were treated at the MTD determined in Phase I.
Recruitment Details
This was an open-label, Phase I/IIa study conducted at 7 study centers in 5 countries in patients with relapsed and/or relapsed-refractory Multiple Myeloma (MM). Overall, 75 patients (23 during Phase I and 52 additional patients during Phase II) were enrolled. The study results are presented until the end of trial (EOT) date of 29 October 2019.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase I: Melflufen 15 mg + Dexamethasone
Patients were treated with 15 milligram (mg) melflufen as intravenous (IV) infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Periods
Title
Milestones
Reasons Not Completed
Phase I (Dose Escalation)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
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 2, 2018
Jun 29, 2020
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
No data available
No data is available for this block.
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Sequential 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
Experimental
IV infusion of 40 mg melflufen on Day 1 of each 21-day or 28-day treatment cycles, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycles. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each treatment cycle.
Drug: Melflufen
Drug: Dexamethasone
Phase II: Melflufen 40 mg (Single Agent)
Experimental
IV infusion of 40 mg melflufen on Day 1 of each 28-day treatment cycle.
Drug: Melflufen
Phase I: Melflufen 55 mg + Dexamethasone
Phase II: Melflufen 40 mg (Single Agent)
Dexamethasone
Drug
Phase I + II: Melflufen 40 mg + Dexamethasone
Phase I: Melflufen 15 mg + Dexamethasone
Phase I: Melflufen 25 mg + Dexamethasone
Phase I: Melflufen 40 mg + Dexamethasone
Phase I: Melflufen 55 mg + Dexamethasone
Clinical Benefit Response Rate (CBRR)
The CBRR was defined as the percentage of patients with a clinical benefit response (CBR), defined as the first occurrence of confirmed disease response including MR or better (i.e, MR, PR, VGPR, CR, or sCR). Starting on completion of Cycle 2, response was assessed according to the IMWG criteria based on the Investigator's assessment for all patients at every cycle during the treatment period. MR was defined as ≥25% but <49% reduction of serum M-protein and reduction in 24 hour urine M-protein by 50 to 89%, which still exceeds 200 mg/24 hours. In addition to above; if present at baseline, 25 to 49% reduction in the size of soft tissue plasmacytomas is also required. No increase in size or number of lytic bone lesions (development of compression fractures does not exclude response). PR was defined as 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by ≥90% or to <200 mg/24 hour.
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to Disease Response in Patients Who Achieved OR and CBR
Time to first OR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of PR or better (first of 2 consecutive assessments-confirmed response). Time to first CBR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of MR or better (first of 2 consecutive assessments-confirmed response). Time to disease response was estimated using Kaplan-Meier statistics.
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to Disease Progression
Time to disease progression was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of evaluable PD. Time to disease progression was estimated using Kaplan-Meier statistics.
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Median Progression-Free Survival (PFS)
The PFS was defined as the time from the date of the first dose of melflufen (overall reference start date) to the date of the first occurrence of any disease response assessment available for PD or death. The PFS was estimated using Kaplan-Meier statistics.
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Median Overall Survival (OS)
The OS was defined as the time from the date of the first dose of melflufen (overall reference start date) to death. The OS was estimated using Kaplan-Meier statistics.
From baseline until death. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to First Subsequent Treatment
Time to first subsequent treatment start was defined as the time from the date of the actual end of treatment to the date of the first subsequent treatment. Time to first subsequent treatment was estimated using Kaplan-Meier statistics.
From baseline until start of first subsequent treatment. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a study patient administered an investigational product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as any AE, occurring at any dose, that met any one or more of the following criteria: is fatal or immediately life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization; or other important medical event. TEAEs were defined as AEs that started or worsened on or after the first dose of study drug (overall reference start date) up to and including the actual EOT date. TESAEs = Treatment emergent serious adverse events.
From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Detroit
Michigan
48201
United States
Universtity of North Carolina
Chapel Hill
North Carolina
27514
United States
Vejle Hospital
Vejle
Denmark
Turin Hospital Myeloma Unit
Turin
Italy
Erasmus University Medical Center
Rotterdam
Netherlands
Sahlgrenska Hospital
Gothenburg
Sweden
FG001
Phase I: Melflufen 25 mg + Dexamethasone
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
FG002
Phase I: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
FG003
Phase I: Melflufen 55 mg + Dexamethasone
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
FG004
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
FG005
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
FG0004 subjects
FG0017 subjects
FG0026 subjects
FG0036 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
Completed 8 cycles or more of study drug.
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0003 subjects
FG0017 subjects
FG0025 subjects
FG0036 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Disease progression
FG0003 subjects
FG0015 subjects
FG0021 subjects
FG0033 subjects
FG0040 subjects
FG0050 subjects
Adverse Event
FG0000 subjects
FG0011 subjects
FG0024 subjects
FG0033 subjects
FG004
Other
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Phase II (MTD)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00445 subjects6 patients were entered from the Phase I: Melflufen 40 mg + Dexamethasone arm.
FG00513 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Phase I: Melflufen 15 mg + Dexamethasone
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
BG001
Phase I: Melflufen 25 mg + Dexamethasone
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
BG002
Phase I: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
BG003
Phase I: Melflufen 55 mg + Dexamethasone
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
BG004
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
BG005
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0004
BG0017
BG0026
BG0036
BG00445
BG00513
BG00681
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
Count of Participants
Participants
No
Title
Denominators
Categories
Phase I
ParticipantsBG0004
ParticipantsBG0017
ParticipantsBG0026
ParticipantsBG003
Sex: Female, Male
6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
Count of Participants
Participants
No
Title
Denominators
Categories
Phase I
ParticipantsBG0004
ParticipantsBG0017
ParticipantsBG002
Race/Ethnicity, Customized
6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
Count of Participants
Participants
No
Title
Denominators
Categories
Phase I
ParticipantsBG0004
ParticipantsBG0017
ParticipantsBG002
Race/Ethnicity, Customized
6 patients from the Phase I: Melflufen 40 mg + Dexamethasone arm were transferred to Phase I + II: Melflufen 40 mg + Dexamethasone arm. All arms for the baseline analysis were not mutually exclusive (mutually exclusive patients = 75).
Count of Participants
Participants
No
Title
Denominators
Categories
Phase I
ParticipantsBG0004
ParticipantsBG0017
ParticipantsBG002
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
Percentage of Patients Who Achieved Best Overall Disease Response
The best overall disease response on treatment including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) or progressive disease (PD) were evaluated. Starting on completion of Cycle 2, response was assessed according to International Myeloma Working Group (IMWG) criteria based on Investigator's assessment for all patients at every cycle during treatment period. PD was defined as increase of ≥25% from lowest response value in any 1 of the following: serum M-component (absolute increase must be ≥0.5 gram/deciliter) and/or urine M-component (absolute increase must be ≥200 mg/24 hr); development of new bone lesions or soft tissue plasmacytomas or increase in size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that could be attributed solely to plasma cell proliferative disorder. SD was defined as not meeting criteria for CR, VGPR, PR or PD.
For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
For Phase II arms: Modified Intent-to-Treat (mITT) Analysis Set included all patients considered to be valid for Safety Analysis Set and who received at least 1 dose of study drug at the MTD as initial dose.
Posted
Number
95% Confidence Interval
percentage of patients
Baseline (Cycle 1 Day 1) and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I: Melflufen 15 mg + Dexamethasone
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG001
Phase I: Melflufen 25 mg + Dexamethasone
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG002
Phase I: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG003
Phase I: Melflufen 55 mg + Dexamethasone
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG004
Phase I + II: Melflufen 40 mg + Dexamethasone
Units
Counts
Participants
OG0004
OG0017
OG0026
OG003
Title
Denominators
Categories
sCR
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG0020.0(0.0 to 45.9)
OG003
Primary
Overall Response Rate (ORR)
ORR was defined as percentage of patients with an overall response (OR), defined as first occurrence of confirmed disease response including PR or better (i.e, PR, VGPR, CR or sCR). Starting on completion of Cycle 2, response was assessed according to IMWG criteria based on Investigator's assessment for all patients at every cycle during treatment period. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum plus urine M-protein level <100 mg/24hr and >90% decrease in difference between involved and uninvolved free light chain (FLC) levels (only in FLC diseased patients). CR was defined as negative immunofixation on serum and urine, loss of any soft tissue plasmacytomas, <5% plasma cells in bone marrow and normal FLC ratio of 0.26 to 1.65 (only in FLC diseased patients). sCR was defined as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or 2 to 4 color flow cytometry.
For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
For Phase II arms: The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose.
Posted
Number
95% Confidence Interval
percentage of patients
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I: Melflufen 15 mg + Dexamethasone
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Primary
Clinical Benefit Response Rate (CBRR)
The CBRR was defined as the percentage of patients with a clinical benefit response (CBR), defined as the first occurrence of confirmed disease response including MR or better (i.e, MR, PR, VGPR, CR, or sCR). Starting on completion of Cycle 2, response was assessed according to the IMWG criteria based on the Investigator's assessment for all patients at every cycle during the treatment period. MR was defined as ≥25% but <49% reduction of serum M-protein and reduction in 24 hour urine M-protein by 50 to 89%, which still exceeds 200 mg/24 hours. In addition to above; if present at baseline, 25 to 49% reduction in the size of soft tissue plasmacytomas is also required. No increase in size or number of lytic bone lesions (development of compression fractures does not exclude response). PR was defined as 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by ≥90% or to <200 mg/24 hour.
For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
For Phase II arms: The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose.
Posted
Number
95% Confidence Interval
percentage of patients
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I: Melflufen 15 mg + Dexamethasone
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Secondary
Duration of Disease Response (DOR)
The DOR to treatment was defined as time from first response (PR or better) to disease progression or death, or date of last evaluable disease response assessment for those who had not progressed or died. DOR was estimated using Kaplan-Meier statistics.
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had achieved at least PR were evaluated.
Posted
Median
95% Confidence Interval
months
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG001
Phase II: Melflufen 40 mg (Single Agent)
Secondary
Time to Disease Response in Patients Who Achieved OR and CBR
Time to first OR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of PR or better (first of 2 consecutive assessments-confirmed response). Time to first CBR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of MR or better (first of 2 consecutive assessments-confirmed response). Time to disease response was estimated using Kaplan-Meier statistics.
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had achieved OR and CBR were evaluated, for each respective time to response parameter.
Posted
Median
95% Confidence Interval
months
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
Secondary
Time to Disease Progression
Time to disease progression was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of evaluable PD. Time to disease progression was estimated using Kaplan-Meier statistics.
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose.
Posted
Median
95% Confidence Interval
months
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG001
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Secondary
Median Progression-Free Survival (PFS)
The PFS was defined as the time from the date of the first dose of melflufen (overall reference start date) to the date of the first occurrence of any disease response assessment available for PD or death. The PFS was estimated using Kaplan-Meier statistics.
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had information about PFS at the time of EOT (29 October 2019) were reported.
Posted
Median
95% Confidence Interval
months
Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG001
Phase II: Melflufen 40 mg (Single Agent)
Secondary
Median Overall Survival (OS)
The OS was defined as the time from the date of the first dose of melflufen (overall reference start date) to death. The OS was estimated using Kaplan-Meier statistics.
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had information about OS at the time of EOT(29 October 2019) were reported.
Posted
Median
95% Confidence Interval
months
From baseline until death. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG001
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Secondary
Time to First Subsequent Treatment
Time to first subsequent treatment start was defined as the time from the date of the actual end of treatment to the date of the first subsequent treatment. Time to first subsequent treatment was estimated using Kaplan-Meier statistics.
The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose. Only patients who had information about first subsequent treatment at the time of EOT (29 October 2019) were reported.
Posted
Median
95% Confidence Interval
months
From baseline until start of first subsequent treatment. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG001
Phase II: Melflufen 40 mg (Single Agent)
Secondary
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a study patient administered an investigational product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as any AE, occurring at any dose, that met any one or more of the following criteria: is fatal or immediately life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization; or other important medical event. TEAEs were defined as AEs that started or worsened on or after the first dose of study drug (overall reference start date) up to and including the actual EOT date. TESAEs = Treatment emergent serious adverse events.
The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
Posted
Count of Participants
Participants
No
From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ID
Title
Description
OG000
Phase I: Melflufen 15 mg + Dexamethasone
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Time Frame
From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Description
The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug.
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
Phase I: Melflufen 15 mg + Dexamethasone
Patients were treated with 15 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
3
4
3
4
4
4
EG001
Phase I: Melflufen 25 mg + Dexamethasone
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
5
7
4
7
7
7
EG002
Phase I: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
2
6
2
6
6
6
EG003
Phase I: Melflufen 55 mg + Dexamethasone
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
5
6
4
6
6
6
EG004
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
30
45
17
45
45
45
EG005
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
10
13
9
13
12
13
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Pneumonia
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG0032 events2 affected6 at risk
EG0045 events5 affected45 at risk
EG0051 events1 affected13 at risk
Bacteraemia
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Cystitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Escherichia bacteraemia
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Sepsis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Bone lesion
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Spinal disorder
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Spinal compression fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Spinal fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Pyrexia
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Hyperphosphataemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Deep vein thrombosis
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Escherichia sepsis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Parainfluenzae virus infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Pseudomonal sepsis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Diabetes mellitus
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Plasmacytoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Spinal cord compression
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0002 events2 affected4 at risk
EG0019 events6 affected7 at risk
EG00226 events4 affected6 at risk
EG00335 events5 affected6 at risk
EG004154 events33 affected45 at risk
EG00530 events9 affected13 at risk
Neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0017 events3 affected7 at risk
EG00212 events3 affected6 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0003 events3 affected4 at risk
EG0015 events4 affected7 at risk
EG0024 events2 affected6 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Anaemia vitamin B12 deficiency
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Increased tendency to bruise
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0026 events4 affected6 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0002 events2 affected4 at risk
EG0013 events3 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0023 events2 affected6 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0022 events2 affected6 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Gastrointestinal disorder
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Fatigue
General disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0015 events3 affected7 at risk
EG0027 events3 affected6 at risk
EG003
Pyrexia
General disorders
MedDRA 20.0
Systematic Assessment
EG0002 events2 affected4 at risk
EG0010 events0 affected7 at risk
EG0022 events2 affected6 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Hyperthermia
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Asthenia
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Chest pain
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Influenza like illness
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Oedema peripheral
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Pain
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0013 events3 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0012 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Osteoporosis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0022 events2 affected6 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0022 events1 affected6 at risk
EG003
Candida infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Cystitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Enterococcal infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Gingivitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Influenza
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Mucosal infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Oral fungal infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Periodontitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Petechiae
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Blood blister
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0012 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0024 events2 affected6 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0013 events3 affected7 at risk
EG0020 events0 affected6 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Blood glucose increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Cardiac murmur
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Protein total increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Nervousness
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0022 events2 affected6 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Headache
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0021 events1 affected6 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0022 events1 affected6 at risk
EG003
Vision blurred
Eye disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Erectile Dysfunction
Reproductive system and breast disorders
MedDRA 20.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Bone marrow failure
Blood and lymphatic system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Application site erosion
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Chills
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Feeling cold
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Mucous membrane disorder
General disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal hernia
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Aerophagia
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Gastric disorder
Gastrointestinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Acarodermatitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Administration site infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Conjunctivitis bacterial
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Eye infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Furuncle
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Herpes virus infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Laryngitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Lung infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Skin infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Myopathy
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Synovial cyst
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
CD4 lymphocytes decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Weight decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Blood lactate dehydrogenase increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Fibrin d dimer increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
International normalised ratio increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Red blood cell count decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Urine output decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Vitamin B12 decreased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Weight increased
Investigations
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Cachexia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Ataxia
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Tremor
Nervous system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Mood altered
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Depression
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Restlessness
Psychiatric disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Spinal compression fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Joint dislocation
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Thermal burn
Injury, poisoning and procedural complications
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hypertension
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hypotension
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Flushing
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Haematoma
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Thrombophlebitis
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Venous thrombosis
Vascular disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Ecchymosis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Mitral valve disease mixed
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Plasmacytoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Ear haemorrhage
Ear and labyrinth disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Immune system disorder
Immune system disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Device occlusion
Product Issues
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 20.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected7 at risk
EG0020 events0 affected6 at risk
EG003
Study is terminated and long-term follow-up ended due to Sponsor decision.
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG005
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
6
OG00445
OG00513
0.0
(0.0 to 45.9)
OG0040.0(0.0 to 7.9)
OG0050.0(0.0 to 24.7)
CR
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG0020.0(0.0 to 45.9)
OG0030.0(0.0 to 45.9)
OG0040.0(0.0 to 7.9)
OG0050.0(0.0 to 24.7)
VGPR
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG00216.7(0.4 to 64.1)
OG00316.7(0.4 to 64.1)
OG00411.1(3.7 to 24.1)
OG0050.0(0.0 to 24.7)
PR
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG00250.0(11.8 to 88.2)
OG0030.0(0.0 to 45.9)
OG00420.0(9.6 to 34.6)
OG0057.7(0.2 to 36.0)
MR
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG0020.0(0.0 to 45.9)
OG0030.0(0.0 to 45.9)
OG00417.8(8.0 to 32.1)
OG00515.4(1.9 to 45.4)
SD
Title
Measurements
OG00075.0(19.4 to 99.4)
OG00142.9(9.9 to 81.6)
OG00216.7(0.4 to 64.1)
OG00366.7(22.3 to 95.7)
OG00426.7(14.6 to 41.9)
OG00569.2(38.6 to 90.9)
PD
Title
Measurements
OG00025.0(0.6 to 80.6)
OG00157.1(18.4 to 90.1)
OG00216.7(0.4 to 64.1)
OG00316.7(0.4 to 64.1)
OG00415.6(6.5 to 29.5)
OG0057.7(0.2 to 36.0)
Missing
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG0020.0(0.0 to 45.9)
OG0030.0(0.0 to 45.9)
OG0048.9(2.5 to 21.2)
OG0050.0(0.0 to 24.7)
sCR + CR
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG0020.0(0.0 to 45.9)
OG0030.0(0.0 to 45.9)
OG0040.0(0.0 to 7.9)
OG0050.0(0.0 to 24.7)
sCR + CR + VGPR
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG00216.7(0.4 to 64.1)
OG00316.7(0.4 to 64.1)
OG00411.1(3.7 to 24.1)
OG0050.0(0.0 to 24.7)
OG001
Phase I: Melflufen 25 mg + Dexamethasone
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG002
Phase I: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG003
Phase I: Melflufen 55 mg + Dexamethasone
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG004
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG005
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Units
Counts
Participants
OG0004
OG0017
OG0026
OG0036
OG00445
OG00513
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG00266.7(22.3 to 95.7)
OG00316.7(0.4 to 64.1)
OG00431.1(18.2 to 46.6)
OG0057.7(0.2 to 36.0)
OG001
Phase I: Melflufen 25 mg + Dexamethasone
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG002
Phase I: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG003
Phase I: Melflufen 55 mg + Dexamethasone
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG004
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG005
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Units
Counts
Participants
OG0004
OG0017
OG0026
OG0036
OG00445
OG00513
Title
Denominators
Categories
Title
Measurements
OG0000.0(0.0 to 60.2)
OG0010.0(0.0 to 41.0)
OG00266.7(22.3 to 95.7)
OG00316.7(0.4 to 64.1)
OG00448.9(33.7 to 64.2)
OG00523.1(5.0 to 53.8)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Units
Counts
Participants
OG00014
OG0011
Title
Denominators
Categories
Title
Measurements
OG0008.4(4.6 to 11.1)
OG0017.2(NA to NA)The confidence interval could not be determined as only 1 patient was analysed.
OG001
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Units
Counts
Participants
OG00022
OG0013
Title
Denominators
Categories
OR
ParticipantsOG00014
ParticipantsOG0011
Title
Measurements
OG0002.8(1.6 to 4.7)
OG0016.7(NA to NA)The confidence interval could not be determined as only 1 patient was analysed.
CBR
ParticipantsOG00022
ParticipantsOG0013
Title
Measurements
OG0002.4(1.4 to 3.0)
OG001
Units
Counts
Participants
OG00045
OG00113
Title
Denominators
Categories
Title
Measurements
OG0006.5(3.7 to 9.3)
OG0014.4(2.8 to 12.2)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Units
Counts
Participants
OG00045
OG00113
Title
Denominators
Categories
Title
Measurements
OG0005.7(3.7 to 9.2)
OG0014.4(2.8 to 7.6)
Units
Counts
Participants
OG00045
OG00113
Title
Denominators
Categories
Title
Measurements
OG00020.7(11.8 to 41.3)
OG00115.5(4.9 to 23.4)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Units
Counts
Participants
OG00045
OG00113
Title
Denominators
Categories
Title
Measurements
OG00010.5(7.9 to 12.2)
OG00110.7(5.3 to NA)Upper limit of confidence could not be calculated as it was not reached.
OG001
Phase I: Melflufen 25 mg + Dexamethasone
Patients were treated with 25 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG002
Phase I: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG003
Phase I: Melflufen 55 mg + Dexamethasone
Patients were treated with 55 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
OG004
Phase I + II: Melflufen 40 mg + Dexamethasone
Patients were treated with 40 mg melflufen as IV infusion on Day 1 and 40 mg dexamethasone oral tablet or IV infusion on Days 1, 8 and 15 of each 21-day or 28-day treatment cycle. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator. In Protocol amendment 4, the cycle of melflufen was increased from 21 to 28 days. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each cycle.
OG005
Phase II: Melflufen 40 mg (Single Agent)
Patients were treated with 40 mg melflufen as IV infusion on Day 1 of each 28-day treatment cycle. Dexamethasone was not administered as an antitumor compound. However, all patients were treated with 8 mg dexamethasone as an antiemetic on Days 1 and 2, and an optional 4 mg dexamethasone as an antiemetic on Days 3 and 4 of the same 28-day cycle, unless the Investigator decided to switch a patient to a combination regimen. Patients could continue receiving treatment for up to 8 cycles or until they experienced unacceptable toxicity, disease progression, withdrew consent, and/or the study drug was discontinued at the discretion of the Investigator.
Units
Counts
Participants
OG0004
OG0017
OG0026
OG0036
OG00445
OG00513
Title
Denominators
Categories
TEAEs (including both serious and non-serious AEs)