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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the maximum tolerated dose of topotecan when administered with carboplatin and fludarabine.
Patients are followed monthly for 6 months.
Brenda W. Cooper, MD
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
United States: Federal Government
|Ireland Cancer Center at University Hospitals Case Medical Center||Cleveland, Ohio 44106-5065|