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

Mayo Clinic

Overview

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.

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Conditions

Leukemia Neutropenia

Interventions

filgrastimBIOLOGICAL

carboplatinDRUG

topotecan hydrochlorideDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Mayo Clinic

Rochester, Minnesota, United States

Data from ClinicalTrials.gov

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