A Randomized Phase II Trial of Oral Topotecan Given Twice a Day for 5 Days or Once a Day for 10 Days to Patients With Myelodysplastic Syndromes (MDS)

OBJECTIVES: I. Estimate complete or partial remission, hematologic improvement, and cytogenic response rate when oral topotecan is given twice a day for 5 days versus once a day for 10 days to patients with myelodysplastic syndromes. II. Evaluate the safety and toxicity of oral topotecan in these patients. III. Evaluate whether there are morphologic and/or cytogenetic subsets of the myelodysplastic syndromes that will respond optimally to this regimen. IV. Evaluate the change in the percentage of bone marrow blast cells in these patients during treatment. V. Evaluate the time to transformation to acute myeloid leukemia (AML) or death in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to FAB subtype: 1. Refractory anemia with excess blasts 2. Refractory anemia with excess blasts in transformation 3. Chronic myelomonocytic leukemia 4. Refractory anemia, refractory anemia with ringed sideroblasts, and refractory cytopenia with multilineage dysplasia Patients are randomized to receive oral topotecan either twice daily for 5 days or once daily for 10 days. Courses are repeated every 21 days. Patients are evaluated for hematologic response after the initial 2 courses, and then every 4 courses. If a partial response or hematologic improvement is observed, treatment continues until disease progression to acute myeloid leukemia, relapse, death, or irreversible toxicity. Patients who achieve a complete response receive an additional 2 courses of therapy before discontinuation of protocol treatment. Patients are followed every 3 months for 2 years, then every year for an additional 3 years, and at time of progression.

PROJECTED ACCRUAL: A total of 90 patients (45 per arm) will be accrued for this study within 13 months.