combination chemotherapy in treating patients with chronic myelogenous leukemia or recurrent acute leukemia

Conditions: Leukemia; Neutropenia

Summary: 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.

Eligibility 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

Keywords: recurrent adult acute myeloid leukemia recurrent adult acute lymphoblastic leukemia relapsing chronic myelogenous leukemia accelerated phase chronic myelogenous leukemia blastic phase chronic myelogenous leukemia neutropenia