Clinical Trial Results:
Open-label, multi-center, single-arm study for the safety and efficacy of pomalidomide (CC-4047) monotherapy for subjects with refractory or relapsed and refractory multiple myeloma: a companion study for clinical trial CC-4047-MM-003
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Summary
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EudraCT number |
2010-023343-16 |
Trial protocol |
BE GB DE ES GR IT CZ NL SE DK |
Global end of trial date |
31 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Jul 2016
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First version publication date |
16 Aug 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CC-4047-MM-003/C
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01324947 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Celgene Corporation
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Sponsor organisation address |
86 Morris Avenue, Summit, United States, 07901
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Public contact |
ClinicalTrialDisclosure, Celgene Corporation, 888 260-1599,
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Scientific contact |
Lars Sternas, Celgene Corporation, ClinicalTrialDisclosure@Celgene.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of pomalidomide (CC-4047) monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who discontinued from Treatment Arm B (dexamethasone alone) of Study CC-4047-MM-003 due to the development of documented disease progression during treatment. Upon discontinuing this study, participants will be followed in the long term follow-up phase of CC-4047-MM-003 study.
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Protection of trial subjects |
Protection of trial subjects through Ethics Committees and Institutional Review Boards
Protection patient confidentiality
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 May 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
Switzerland: 4
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
Australia: 5
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Canada: 8
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Country: Number of subjects enrolled |
France: 18
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Country: Number of subjects enrolled |
Germany: 10
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Country: Number of subjects enrolled |
Greece: 5
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Russian Federation: 3
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Worldwide total number of subjects |
74
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EEA total number of subjects |
54
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
33
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From 65 to 84 years |
40
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
CC-4047-MM003C is a companion study for the trial CC-4047-MM-003. CC-4047-MM-003C enrolled participants who had discontinued treatment with dexamethasone alone (Treatment Arm B) in the CC-4047-MM-003 trial due to disease progression; those who had discontinued treatment with pomalidomide plus dexamethasone (Arm A) were not eligible to participate. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Arm title
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Pomalidomide | ||||||||||||||||||||||||
Arm description |
Oral pomalidomide 4 mg capsule on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Pomalidomide
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Investigational medicinal product code |
CC-4047
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Other name |
Imnovid; Pomalyst
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Oral Pomalidomide 4mg capsules by mouth (PO) on Days 1 through 21 of each 28 day cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
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End points reporting groups
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Reporting group title |
Pomalidomide
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Reporting group description |
Oral pomalidomide 4 mg capsule on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity | ||
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End point title |
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment [1] | ||||||||
End point description |
Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment.
SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas
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End point type |
Primary
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End point timeframe |
From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The study is a single-armed trial, no statistical analysis was done due to lack of a comparator. |
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| Notes [2] - Intent to Treat Population was defined as all enrolled participants. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment | ||||||||
End point description |
Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the CR and requires all of the following:
• Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days.
• <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed.
• No increase in size or number of lytic bone lesions.
• Disappearance of soft tissue plasmacytomas.
PR requires all of the following:
• ≥50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days.
• Reduction in 24-hour urinary light chain extraction by ≥90% or to <200 mg, maintained at least 42 days.
• For patients with non-secretory myeloma, ≥50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days.
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End point type |
Secondary
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End point timeframe |
From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.
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| Notes [3] - Intent to treat population includes all participants enrolled. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Adverse Events (AEs) and Type of Adverse Events | ||||||||||||||||||||||||||||||||||||
End point description |
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that:
• Results in death;
• Is life-threatening;
• Requires or prolongs existing inpatient hospitalization;
• Results in persistent or significant disability/incapacity;
• Is a congenital anomaly/birth defect;
• Constitutes an important medical event.
The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity); medical intervention needed, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death
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End point type |
Secondary
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End point timeframe |
From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.
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| Notes [4] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG | ||||||||
End point description |
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Investigator based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier.
Progressive disease requires 1 of the following:
• Increase of ≥ 25% from nadir in:
o Serum M-component (absolute increase ≥ 0.5 g/dl)
o Urine M-component (absolute increase ≥ 200 mg/24 hours)
o In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl)
o Bone marrow plasma cell percentage (absolute % ≥ 10%)
• Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas
Intent to Treat included all participants enrolled
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End point type |
Secondary
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End point timeframe |
From randomization through the follow-up phase; Maximum duration of follow-up for PFS was 90.3 weeks.
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| No statistical analyses for this end point | |||||||||
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End point title |
Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria | ||||||||
End point description |
Time to progression (TTP) was calculated as the time from randomization to the first documented progression confirmed by the investigator and based on the International Myeloma Working Group Uniform Response criteria (IMWG).
Progressive disease requires 1 of the following:
o Increase of ≥ 25% from nadir in:
o Serum M-component (absolute increase ≥ 0.5 g/dl)
o Urine M-component (absolute increase ≥ 200 mg/24 hours)
o In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl)
o Bone marrow plasma cell percentage (absolute % ≥ 10%)
o Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.
o Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
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End point type |
Secondary
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End point timeframe |
From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to progression follow-up was 90.3 weeks.
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| No statistical analyses for this end point | |||||||||
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End point title |
Kaplan-Meier Estimate of Duration of Response Based on Investigator Assessment Using IMWG Criteria | ||||||||
End point description |
Duration of Response (calculated for responders only) is defined as the time from the initial documented response (partial response or better) to confirmed disease progression by the investigator based on IMWG criteria.
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End point type |
Secondary
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End point timeframe |
From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum duration of response follow-up was 90.3 weeks.
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| Notes [5] - Includes those who had a partial response or better |
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| No statistical analyses for this end point | |||||||||
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End point title |
Kaplan-Meier Estimate for Overall Survival | ||||||||
End point description |
Overall survival was calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
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End point type |
Secondary
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End point timeframe |
From randomization through the follow-up phase; Maximum time on follow-up was 141.1 weeks.
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| Notes [6] - Intent to Treat population included all participants enrolled into the study |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Response Based on IMWG and Assessed by the Investigator | ||||||||
End point description |
Time to Response was calculated only for participants with a PR or better based on IMWG and assessed by the investigator.
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End point type |
Secondary
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End point timeframe |
Randomization through the follow-up phase; up to the data-cut off: 31 July 2014; Maximum time to response was 23.1 weeks
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| Notes [7] - Includes those who had at least a partial response or better; Intent to Treat |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14
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Reporting groups
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Reporting group title |
Pomalidomide
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Reporting group description |
Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Jun 2011 |
The global amendment consisted of the following:
1. Required that Secondary Primary Malignancy (SPMs) be treated as SAEs and reported throughout the study duration, including long-term follow-up.
2. Lowered the eligibility requirement for measurable level of serum M-protein from 1.0 g/dL to 0.5 g/dL, since this patient population was heavily pre-treated.
3. Updated exclusion criterion for serum total bilirubin to allow for higher level at study entry for subjects with hereditary enzymatic disorders such as Gilbert syndrome, glucose-6-phosphate dehydrogenase deficiency, etc., who had a mild increase in total bilirubin primarily due to increase of indirect bilirubin.
4. For exclusion criterion related to hypersensitivity to thalidomide or lenalidomide, specified that ≥ Grade 3 rash during prior thalidomide or lenalidomide treatment was considered hypersensitivity.
5. Eligibility for subjects with prior allogeneic bone marrow or allogeneic peripheral blood stem cell transplant was revised so that subjects could enter the study if at least 12 months had elapsed since their transplant or if they were not receiving concomitant immunosuppressive medications related to the transplant at the time of study entry.
6. Clarified pomalidomide dose modification instructions for neutropenia and
thrombocytopenia. |
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04 Nov 2011 |
The global amendment consisted of the following changes:
1. Required that subjects with a prior history of malignancies, other than MM, be free of the disease for ≥ 5 years rather than ≥ 3 years.
2. Updated inclusion criterion to allow subjects to become eligible for the companion study after starting the second cycle of High-Dose dexamethasone (HD-dex) in the core Study CC-4047-MM-003, rather than completing the second cycle of HD-dex.
3. Updated screening requirements to reflect that, in addition to the use of growth factors, the use of platelet and/or RBC transfusions were allowed throughout the study, including the screening period, at the discretion of the investigator. However, subjects who failed screening as a result of neutropenia, thrombocytopenia, or anemia were not permitted to use growth factors, platelet or RBC transfusions to become eligible.
4. Updated to reflect that subjects who had a creatinine clearance less than 45 mL/min by the Cockcroft-Gault method at screening and/or Cycle 1 Day 1, an evaluation of creatinine clearance would be performed using the 24-hour urine sample from the urine M-protein collection. The Cockcroft-Gault method was used for the remainder of the study.
5. Subjects were no longer required to have 14-day wash-out of steroids for entry into the study.
6. Updated exclusion criterion # 9 to reflect that subjects who had not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment (rather than 12 months) and were currently dependent on such treatment would not be eligible for the study.
7. Updated the dose modification instructions for hematologic toxicities based on CTCAE version 4.0 for febrile neutropenia: ANC < 1,000/μL with a single temperature of > 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour. |
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12 Dec 2012 |
The global amendment consisted of the following:
1. Clarified that Low-dose dexamethasone (LD-dex) was a permitted concomitant medication.
2. Revised the language explaining abstinence as a method of contraception to ensure consistency across all Immunomodulatory (IMiD) studies.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
