Combination Chemotherapy in Treating Patients With Chronic Myelogenous Leukemia or Recurrent Acute Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy with carboplatin and topotecan in treating patients with chronic myelogenous leukemia or recurrent acute leukemia.

Detailed Description
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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.

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

Conditions
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Leukemia, Neutropenia

Intervention / Treatment
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* Biological: filgrastim
* Drug: carboplatin
* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: carboplatin|nan|
|Drug: topotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neutropenia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia