Phase I Study of Fludarabine, Carboplatin, and Topotecan for Patients With Relapsed/Refractory Acute Leukemia and Advanced Myelodysplastic Syndromes

OBJECTIVES: I. Determine the maximum tolerated dose of topotecan when administered with carboplatin and fludarabine in patients with refractory or relapsed acute leukemia or advanced myelodysplastic syndrome. II. Determine treatment related and dose limiting toxicities of this regimen in these patients. III. Determine the antileukemia activity of this regimen in these patients. IV. Correlate treatment related toxicities with steady state levels of topotecan in these patients.

OUTLINE: This is a dose escalation study of topotecan. Patients receive carboplatin IV continuously and fludarabine IV over 30 minutes on days 1-5, then topotecan IV continuously on days 6-8. Patients with residual leukemia in the bone marrow at day 15 may receive a second induction course. Patients who achieve partial or complete remission after 1-2 induction courses receive 1 consolidation course of fludarabine, carboplatin, and topotecan beginning 4-8 weeks after recovery from induction therapy. Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The first 3 patients do not receive any topotecan. The MTD is defined as the dose at which no more than 2 of 6 patients experience dose limiting toxicity. Patients are followed monthly for 6 months.

PROJECTED ACCRUAL: A total of 6-15 patients will be accrued for this study within 15-21 months.