PHASE I STUDY OF CONTINUOUS INFUSION CARBOPLATIN AND TOPOTECAN IN THE TREATMENT OF RELAPSED ACUTE LEUKEMIA AND BLAST CRISIS CHRONIC MYELOGENOUS LEUKEMIA
filgrastim
+ carboplatin
+ topotecan hydrochloride
Cytopenia+27
+ Agranulocytosis
+ Bone Marrow Diseases
Treatment Study
Summary
Study start date: October 1, 1995
Actual date on which the first participant was enrolled.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. 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 treatment. 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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Acute lymphocytic or myeloid leukemia (ALL or AML) in 1 of the following categories: Failed to achieve a complete response (CR) with initial induction regimen First relapse within 1 year of initial CR Failed re-induction therapy at first relapse Second relapse after no more than 2 different induction regimens Relapse defined as more than 10% blasts in marrow or circulating blasts in peripheral blood and either: Symptoms of recurrence (e.g., B symptoms) Evidence of impending marrow failure (i.e., cytopenias) OR Chronic myelogenous leukemia in accelerated or blastic phase after no more than 1 prior induction regimen No HLA-identical sibling marrow donor or patient ineligible for allogeneic marrow transplantation No clinical symptoms of CNS leukemia Patients with history of CNS leukemia must have pretreatment lumbar puncture demonstrating absence of active CNS disease No active CNS disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 4 weeks Hematologic: Not applicable Hepatic: Bilirubin less than 2 mg/dL Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No congestive heart failure No poorly controlled arrhythmia No myocardial infarction within the past 3 months Other: No active infection No other serious medical condition that would prevent compliance Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics At least 24 hours since prior hydroxyurea for impending leukostasis No concurrent hydroxyurea glucocorticoids Recovered from prior chemotherapy Endocrine therapy: At least 24 hours since prior glucocorticoids for impending leukostasis At least 7 days since prior amphotericin or aminoglycosides No concurrent glucocorticoids Radiotherapy: Not specified Surgery: Not specified Other: No concurrent aminoglycoside antibiotics
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location