Lenalidomide With or Without Epoetin Alfa in Treating Patients With Myelodysplastic Syndrome and Anemia

Description

PRIMARY OBJECTIVE:

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.

SECONDARY OBJECTIVES:

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 relation 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:

VIIIa. Pretreatment and on study endogenous erythropoietin level (Arm A). VIIIb. To evaluate the effect of CD45 isoform profile on lenalidomide enhancement of erythropoietin-induced STAT5 phosphorylation in CD71^Hi erythroid precursors and the relationship to erythroid response.

VIIIc. To characterize molecular targets relevant to lenalidomide cytotoxicity in del5q31.1 cells.

VIIId. 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. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

ARM B: Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa subcutaneously (SC) once weekly. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

In both arms, treatment repeats every 28 days for 4 cycles. Patients who achieve a major erythroid response (MER) may continue treatment beyond 4 cycles 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.