Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00179621
Status:
COMPLETED
Last Update Posted:
2011-04-14
First Post:
2005-09-10
Brief Title:
Lenalidomide Versus Placebo in Myelodysplastic Syndromes With a Deletion 5q31 Abnormality
Sponsor:
Celgene Corporation
Organization:
Celgene
Study Overview
Official Title:
A Multicenter Randomized Double-Blind Placebo-Controlled 3-Arm Study of the Efficacy and Safety of 2 Doses of Lenalidomide Versus Placebo in Red Blood Cell RBC Transfusion-Dependent Subjects With Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated With a Deletion Del 5q31 Cytogenetic Abnormality
Status:
COMPLETED
Status Verified Date:
2011-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study was to compare 2 doses 10 mg and 5 mg of lenalidomide to that of placebo in subjects with red blood cell RBC transfusion-dependent low- or intermediate-1-risk IPSS MDS associated with a deletion del 5q31 cytogenetic abnormality Study participants were randomized to one of the two treatment groups or to placebo and took the study drug for 16 weeks At this timepoint participants were evaluated for erythroid response If participants did not achieve at least a minor erythroid response they were discontinued from the Double-Blind phase and entered into the Open-Label phase All erythroid responders at Week 16 were to continue in the Double-Blind phase for up to 52 weeks For participants that were still responding at the end of Double-Blind phase they could then rollover into the Open-Label phase for an additional two years Participants could remain on study for up to a total of 3 years All participants who discontinued from the study were followed every 4 months for overall survival and progression to acute myeloid leukemia AML
Detailed Description:
MDS-004 was a multicenter randomized double-blind placebo-controlled 3-arm study of 2 doses of lenalidomide versus placebo administered to RBC transfusion-dependent adults with low- or intermediate-1 risk MDS associated with a del 5q31 cytogentetic abnormality Potential participants that had a del 5q31 cytogenetic abnormality plus other additional cytogenetic abnormalities were also eligible for enrollment Transfusion-dependent anemia was defined as documentation that a participant with anemia due to MDS did not have any consecutive 56 days 8 weeks that were RBC transfusion free during at least the 112 days 16 weeks prior to Day 1 of the Pre-Randomization Phase
This study was conducted in three phases
1 a Pre-Randomization Phase
2 a Double-Blind Treatment Phase
3 an Open-Label Extension Phase
Potentially protocol-eligible participants entered the Pre-Randomization Phase and were evaluated for the inclusion and exclusion criteria for the Double-Blind Treatment Phase The Pre-Randomization Phase was not to last for more than 56 days 8 weeks When the participants baseline RBC transfusion requirement was calculated and it had been determined that all eligibility criteria had been met the participant could be randomized for treatment in the Double-Blind Treatment Phase at the time of their next RBC transfusion This RBC transfusion had to occur within 56 days of the participants last previous RBC transfusion
Participants meeting eligibility criteria were randomized 111 ratio to receive either lenalidomide 10 mgday on days 1-21 lenalidomide 5 mgday on days 1-28 or placebo on days 1-28 all on a 28-day cycle Randomization was performed using a validated interactive voice response system Participants were stratified according to karyotype IPSS karyotype score 0 vs 0 ie isolated del 5q31 vs del 5q31 plus 1 additional cytogenetic abnormality A complete blood count CBC serum or plasma ferritin and EPO levels were measured to determine baseline levels
Participants who achieved at least a minor erythroid response ie 50 decrease in transfusion requirements by week 16 could continue treatment in the Double-Blind phase for up to 52 weeks unless there was evidence of erythroid relapse disease progression or unacceptable toxicity Those who did not achieve at least a minor erythroid response by week 16 were discontinued from the Double-Blind phase for lack of therapeutic efficacy and unblinded and were potentially eligible for Open-Label treatment All participants who completed the double-blind treatment phase the first 52 weeks of the trial without disease progression or erythroid relapse were unblinded and entered the Open-Label extension phase at their current lenalidomide dose Participants in the placebo or lenalidomide 5 mg arms who failed to achieve at least a minor erythroid response by week 16 or who had an erythroid relapse could cross over to lenalidomide 5 mg or 10 mg respectively in the Open-Label Extension phase
Lenalidomide treatment could be continued in the Open-label Extension phase for up to 3 years 156 weeks of total study participation Participants with disease progression at any time and participants in the lenalidomide 10 mg group who did not achieve at least a minor erythroid response by week 16 were withdrawn from the study and were ineligible for Open-Label treatment
Serial measurements for efficacy and safety were performed every 28 days In addition CBCs were monitored weekly for the first 8 weeks every 2 weeks for the next 8 weeks and every 4 weeks thereafter Bone marrow aspirate BMA and standard cytogenetic studies were performed at baseline weeks 12 week 24 and every 24 weeks thereafter and when clinically indicated for assessment of disease progression BMAs were submitted for central pathology review and sent to a central cytogenetics laboratory for processing and review All participants were followed for overall survival OS and progression to acute myeloid leukemia AML
Lenalidomide or placebo dosing was reduced for dose-limiting toxicities according to the following dose reduction schedule
Lenalidomide 5 mg starting dose
dose level -1 5 mg every other day
dose level -2 5 mg twice a week
dose level -3 5 mg weekly
Lenalidomide 10 mg starting dose
dose level -1 5 mg daily
dose level -2 5 mg every other day
dose level -3 5 mg twice a week
Participants who could not tolerate dose level -3 discontinued treatment For grade 4 neutropenia lenalidomide was required per protocol to be interrupted and resumed at a decreased dose level when the absolute neutrophil count ANC recovered to 500μL For grade 4 thrombocytopenia lenalidomide was interrupted and then resumed at a decreased dose level when the platelet count recovered to between 25000μL and 50000μL on at least 2 occasions for 7 days or 50000 at any time respectively Prophylactic and therapeutic use of granulocyte colony-stimulating factors G-CSF or granulocyte macrophage colony-stimulating factors GM-CSF was allowed
This study was conducted in three phases
1 a Pre-Randomization Phase
2 a Double-Blind Treatment Phase
3 an Open-Label Extension Phase
Potentially protocol-eligible participants entered the Pre-Randomization Phase and were evaluated for the inclusion and exclusion criteria for the Double-Blind Treatment Phase The Pre-Randomization Phase was not to last for more than 56 days 8 weeks When the participants baseline RBC transfusion requirement was calculated and it had been determined that all eligibility criteria had been met the participant could be randomized for treatment in the Double-Blind Treatment Phase at the time of their next RBC transfusion This RBC transfusion had to occur within 56 days of the participants last previous RBC transfusion
Participants meeting eligibility criteria were randomized 111 ratio to receive either lenalidomide 10 mgday on days 1-21 lenalidomide 5 mgday on days 1-28 or placebo on days 1-28 all on a 28-day cycle Randomization was performed using a validated interactive voice response system Participants were stratified according to karyotype IPSS karyotype score 0 vs 0 ie isolated del 5q31 vs del 5q31 plus 1 additional cytogenetic abnormality A complete blood count CBC serum or plasma ferritin and EPO levels were measured to determine baseline levels
Participants who achieved at least a minor erythroid response ie 50 decrease in transfusion requirements by week 16 could continue treatment in the Double-Blind phase for up to 52 weeks unless there was evidence of erythroid relapse disease progression or unacceptable toxicity Those who did not achieve at least a minor erythroid response by week 16 were discontinued from the Double-Blind phase for lack of therapeutic efficacy and unblinded and were potentially eligible for Open-Label treatment All participants who completed the double-blind treatment phase the first 52 weeks of the trial without disease progression or erythroid relapse were unblinded and entered the Open-Label extension phase at their current lenalidomide dose Participants in the placebo or lenalidomide 5 mg arms who failed to achieve at least a minor erythroid response by week 16 or who had an erythroid relapse could cross over to lenalidomide 5 mg or 10 mg respectively in the Open-Label Extension phase
Lenalidomide treatment could be continued in the Open-label Extension phase for up to 3 years 156 weeks of total study participation Participants with disease progression at any time and participants in the lenalidomide 10 mg group who did not achieve at least a minor erythroid response by week 16 were withdrawn from the study and were ineligible for Open-Label treatment
Serial measurements for efficacy and safety were performed every 28 days In addition CBCs were monitored weekly for the first 8 weeks every 2 weeks for the next 8 weeks and every 4 weeks thereafter Bone marrow aspirate BMA and standard cytogenetic studies were performed at baseline weeks 12 week 24 and every 24 weeks thereafter and when clinically indicated for assessment of disease progression BMAs were submitted for central pathology review and sent to a central cytogenetics laboratory for processing and review All participants were followed for overall survival OS and progression to acute myeloid leukemia AML
Lenalidomide or placebo dosing was reduced for dose-limiting toxicities according to the following dose reduction schedule
Lenalidomide 5 mg starting dose
dose level -1 5 mg every other day
dose level -2 5 mg twice a week
dose level -3 5 mg weekly
Lenalidomide 10 mg starting dose
dose level -1 5 mg daily
dose level -2 5 mg every other day
dose level -3 5 mg twice a week
Participants who could not tolerate dose level -3 discontinued treatment For grade 4 neutropenia lenalidomide was required per protocol to be interrupted and resumed at a decreased dose level when the absolute neutrophil count ANC recovered to 500μL For grade 4 thrombocytopenia lenalidomide was interrupted and then resumed at a decreased dose level when the platelet count recovered to between 25000μL and 50000μL on at least 2 occasions for 7 days or 50000 at any time respectively Prophylactic and therapeutic use of granulocyte colony-stimulating factors G-CSF or granulocyte macrophage colony-stimulating factors GM-CSF was allowed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2005-000454-73 | EUDRACT_NUMBER | None | None |