Lenalidomide With or Without Epoetin Alfa in Treating Patients With Myelodysplastic Syndrome and Anemia
|Anemia Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndrome Previously Treated Myelodysplastic Syndrome||Biological: Epoetin Alfa Other: Laboratory Biomarker Analysis Drug: Lenalidomide||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
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 ]
- Bone marrow response (complete response and partial response) rate [ Time Frame: Up to 6 months ]90% confidence Interval will be calculated by treatment arm.
- Cytogenetic response rate [ Time Frame: Up to 6 months ]Calculated by treatment arm among patients with cytogenetic abnormalities, along with its 90% confidence interval.
- 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 [ Time Frame: 8 weeks ]Summarized by Kaplan-Meier method for patients who achieve MER by treatment arms.
- Minor erythroid response rate [ Time Frame: 8 weeks ]Compared between treatment arms by Fisher's exact test.
- Rate of MER [ Time Frame: Up to 6 months ]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.
- Time to MER [ Time Frame: From randomization to the documented date of MER, assessed up to 16 weeks ]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.
|Actual Study Start Date:||January 29, 2009|
|Estimated Primary Completion Date:||September 1, 2017 (Final data collection date for primary outcome measure)|
Active Comparator: Arm A (lenalidomide)
Patients receive lenalidomide PO QD on days 1-21.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Lenalidomide
Experimental: Arm B (lenalidomide, epoetin alfa)
Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly.
Biological: Epoetin Alfa
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Lenalidomide
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-/intermediate-1 (Int-1)-risk myelodysplastic syndrome (MDS) patients or erythropoietin treatment naïve 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 [CR] + partial response [PR]).
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 cluster of differentiation (CD)45 isoform profile on lenalidomide enhancement of erythropoietin-induced signal transducer and activator of transcription 5A (STAT5) phosphorylation in CD71^Hi 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: Patients are randomized to 1 of 2 treatment arms. Patients with del 5q31.1 karyotype are assigned to Arm A.
ARM A: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21.
ARM B: 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 A 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 B.
After completion of study treatment, patients are followed up for 6 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00843882
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|Principal Investigator:||Alan List||ECOG-ACRIN Cancer Research Group|