PHASE I STUDY OF CONTINUOUS INFUSION CARBOPLATIN AND TOPOTECAN IN THE TREATMENT OF RELAPSED ACUTE LEUKEMIA AND BLAST CRISIS CHRONIC MYELOGENOUS LEUKEMIA
- 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
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
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.
- Consolidation (begins around day 42 of last Induction course): Patients with ALL/AML in
complete remission (CR) or CML in chronic phase receive 2 additional courses (same
doses) 6-8 weeks apart.
Patients experiencing a relapse after CR lasting at least 6 months may receive additional
PROJECTED ACCRUAL: A total of 15-20 patients without and 2-20 patients with prior bone
marrow transfer will be accrued for this study over 2-2.5 years.
Primary Purpose: Treatment
Scott H. Kaufmann, MD, PhD
United States: Federal Government
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