PHASE I STUDY OF CONTINUOUS INFUSION CARBOPLATIN AND TOPOTECAN IN THE TREATMENT OF RELAPSED ACUTE LEUKEMIA AND BLAST CRISIS CHRONIC MYELOGENOUS LEUKEMIA

OBJECTIVES:

• Estimate the maximum tolerated dose of carboplatin plus topotecan given as a 5-day continuous infusion in patients with recurrent acute lymphocytic or myeloid leukemia or accelerated or blastic phase chronic myelogenous leukemia.
• Assess the toxicity of this regimen in these patients.
• Gather preliminary information on the activity of this regimen in these patients.
• Examine the pharmacokinetics of topotecan when administered concurrently with carboplatin.

OUTLINE: This is a dose escalation study of topotecan. Patients are stratified according to prior bone marrow transplant (BMT) (yes vs no).

• Induction: Patients receive carboplatin and topotecan IV 3 times a day on days 1-5. Patients may also receive filgrastim (G-CSF) beginning on day 7 or 14. Retreatment is based on results of marrow exam on day 10-14. Patients with less than 5% blasts undergo a second marrow exam upon blood count recovery or on day 26-30, whichever is earlier. Patients with at least 5% blasts after day 21 receive one more course, in the absence of unacceptable toxicity and at the discretion of the investigator. Patients with no greater than 5% blasts begin G-CSF if blood counts are not recovered, then proceed to consolidation.

Cohorts of 1-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of up to 6 patients experience dose limiting toxicity. Patients with prior BMT will not be entered at any level until 3-6 patients with no prior BMT tolerate that level.