Lenalidomide With or Without Epoetin Alfa in Treating Patients With Myelodysplastic Syndrome and Anemia
This randomized phase III trial studies lenalidomide to see how well it works with or without epoetin alfa in treating patients with myelodysplastic syndrome and anemia. Lenalidomide may stop the growth of myelodysplastic syndrome by blocking blood flow to the cell. Colony stimulating factors, such as epoetin alfa, may increase the number of immune cells found in bone marrow or peripheral blood. It is not yet known whether lenalidomide is more effective with or without epoetin alfa in treating patients with myelodysplastic syndrome and anemia.
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Biological: epoetin alfa
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Phase III Trial Comparing the Frequency of Major Erythroid Response (MER) to Treatment With Lenalidomide (Revlimid®) Alone and in Combination With Epoetin Alfa (Procrit®) in Subjects With Low- or Intermediate-1 Risk MDS and Symptomatic Anemia|
- MER defined as sustained transfusion independence in transfusion-dependent patients or a rise in hemoglobin > 2 g/dL in transfusion-independent patients with anemia for a minimum of 8 consecutive weeks [ Time Frame: At 16 weeks ] [ Designated as safety issue: No ]
- Time to MER [ Time Frame: From randomization to the documented date of MER, assessed up to 16 weeks ] [ Designated as safety issue: No ]Time to MER will be compared between lenalidomide monotherapy and combined treatment of lenalidomide and epoetin alfa in MER responders, using a one-sided log-rank test at the significance level of 0.025.
- Duration of MER defined as the time interval between the documented date of MER and the earliest date of resumption of RBC transfusions > 2 units a reduction in hemoglobin concentration >= 2 g/dL in the absence of acute infection [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Summarized by Kaplan-Meier method for patients who achieve MER by treatment arms.
- Rate of MER [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]The 90% confidence interval of the rate of MER to salvage combination therapy will be computed in patients who fail to achieve an MER with lenalidomide monotherapy and cross over to the combination therapy.
- Minor erythroid response rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Compared between treatment arms by Fisher's exact test.
- Cytogenetic response rate [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]Calculated by treatment arm among patients with cytogenetic abnormalities, along with its 90% confidence interval.
- Bone marrow response (complete response and partial response) rate [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]90% confidence Interval will be calculated by treatment arm.
|Study Start Date:||January 2009|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Active Comparator: Arm I (lenalidomide)
Patients receive lenalidomide PO QD on days 1-21.
Given POOther: laboratory biomarker analysis
Experimental: Arm II (lenalidomide, epoetin alfa)
Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
Given POBiological: epoetin alfa
Given SCOther: laboratory biomarker analysis
I. To compare the rate of major erythroid response (MER) between lenalidomide monotherapy and combined treatment of lenalidomide and epoetin alfa in erythropoietin non-responsive low- or intermediate-1-risk myelodysplastic syndrome (MDS) patients or erythropoietin treatment naive patients with low probability of erythropoietin benefit.
I. To compare the time to MER by treatment assignment. II. To evaluate the duration of MER by treatment assignment. III. To estimate the frequency of MER to salvage combination therapy in patients who fail to experience a MER with lenalidomide monotherapy.
IV. To evaluate and compare the frequency of minor erythroid response by treatment assignment.
V. To investigate the mechanism and target of lenalidomide action in patients with chromosome 5q31.1 deletion.
VI. To evaluate the frequency of cytogenetic response and progression, and the relationship between cytogenetic pattern and erythroid response.
VII. To evaluate the frequency of bone marrow response (complete response and partial response).
VIII. To evaluate the relationship between erythroid response and laboratory correlates outlined below:
- Pretreatment and on study endogenous erythropoietin level (Arm A).
- To evaluate the effect of CD45 isoform profile on lenalidomide enhancement of erythropoietin-induced STAT5 phosphorylation in CD71Hi erythroid precursors and the relationship to erythroid response.
- To characterize molecular targets relevant to lenalidomide cytotoxicity in del5q31.1 cells.
- To evaluate the frequency of cryptic chromosome 5q31.1 deletions in patients with non-del5q31.1 MDS by array-based genomic scan, and to determine the relationship to hematologic response.
OUTLINE: This is a multicenter study. Patients are stratified according to erythropoietin level (=< 500 mU/mL vs > 500 mU/mL) and prior erythropoietic growth factor (yes vs no). Patients are randomized to 1 of 2 treatment arms. Patients with del 5q31.1 karyotype are assigned to treatment arm I.
ARM I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21.
ARM II: Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa subcutaneously (SC) once weekly.
In both arms, treatment repeats every 28 days for 4 courses. Patients who achieve a major erythroid response (MER) may continue treatment beyond 4 courses in the absence of disease progression, disease conversion to acute myeloid leukemia, or unacceptable toxicity. Patients in arm I who fail to achieve MER or who achieve MER but relapse after 16 weeks of treatment with lenalidomide may crossover and receive treatment in arm II.
After completion of study treatment, patients are followed for 6 months.