Phase 3 N=205 Randomized Quadruple-blind Treatment

Lenalidomide Versus Placebo in Myelodysplastic Syndromes With a Deletion 5q[31] Abnormality

Myelodysplastic Syndromes

Bottom Line

View on ClinicalTrials.gov: NCT00179621 ↗

Enrolled (actual)

205

Serious AEs

50.2%

Results posted

Mar 2011

Primary outcome: Primary: Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days) — 3; 20; 23 Participants — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Lenalidomide 5 mg (Drug); Lenalidomide 10 mg (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Celgene Corporation
Primary completion: Jun 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days)	3; 20; 23	<0.001 sig
SECONDARY Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for 56 Days	4; 24; 25	<0.001 sig
SECONDARY Duration of Red Blood Cell (RBC) Transfusion Independence for Participants Who Became RBC Transfusion Independent for at Least 182 Days	61.4; 107.7; 108.6	—
SECONDARY Maximum Change From Baseline in Hemoglobin During the Double-blind Period for Participants Who Became Red Blood Cell (RBC) Transfusion Independent for at Least 182 Days	2.0; 5.5; 6.0	—
SECONDARY Participants' Response in Platelet Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period	0; 1; 1; 0; 0; 0	—
SECONDARY Participants' Response in Absolute Neutrophil Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period	1; 3; 2; 0; 0; 1	—
SECONDARY Participants' Response Based on Bone Marrow Samples by the International MDS Working Group (IWG 2000) During Double-blind Period	0; 7; 12; 0; 5; 1	—
SECONDARY Participants Showing Cytogenetic Response by the International MDS Working Group (IWG 2000) During Double-blind Period as Evaluated by Central Review	0; 5; 10; 0; 3; 7	—
SECONDARY Participants Who Progressed to Acute Myeloid Leukemia (AML) During the Study	2; 2; 0; 4; 7; 2	—
SECONDARY Kaplan Meier Estimates of Overall Survival by Randomized Group	42.4; NA; 44.5	—
SECONDARY Participant Count of Deaths During Double-blind and Open-label by Randomized Group	35; 32; 34	—
SECONDARY Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Week 12	-2.5; 5.9; 5.8	<0.05 sig
SECONDARY Change From Baseline in the Trial Outcome Index-Anemia (TOI-An) Endpoints at Week 12	-1.1; 5.6; 4.9	0.054
SECONDARY Change From Baseline in the Trial Outcome Index-Fatigue (TOI-F) Endpoints at Week 12	-0.8; 4.8; 3.9	0.062
SECONDARY Summary of Participants Who Had Adverse Events (AE) During the Double-blind Period	64; 69; 69; 34; 68; 66	—

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) 5q[31] 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).

Eligibility Criteria

Inclusion Criteria

Must understand and voluntarily sign an informed consent form
Age 18 years at the time of signing the informed consent form
Documented diagnosis of myelodysplastic syndromes (MDS) that meets International Prognostic Scoring System (IPSS) criteria for low to intermediate-1-risk disease and has an associated del 5q(31) cytogenetic abnormality
Red blood cell (RBC) transfusion dependent anaemia defined as not having any 56 days without a RBC transfusion within at least the immediate 112 days
Must be able to adhere to the study visit schedule and other protocol requirements
Women of childbearing potential must have a negative pregnancy test prior to inclusion

Exclusion Criteria

Pregnant or lactating females
Prior therapy with lenalidomide
Proliferative (white blood cell (WBC)= 12, 000/mL) chronic myelomonocytic leukemia (CMML)
Prior >= grade-2 (using the National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) (v 3.0)) allergic reaction to thalidomide
Prior desquamating (blistering) rash while taking thalidomide
Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for >3 years
Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days
Less than 6 months since prior allogeneic bone marrow transplantation
Less than 3 months since prior autologous bone marrow or stem cell transplantation
Less than 28 days since prior myelosuppressive anticancer biologic therapy
Recombinant human erythropoietin (rHuEPO) therapy received within 28 days
Known human immunodeficiency virus (HIV-1) positivity
Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00179621). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.