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

Purpose:

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.

Study summary:

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.

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 is Available At:

Original ID:

CDR0000064447

NCT ID:

NCT00002693

Secondary ID:

U01CA069912

Study Acronym:

Brief Title:

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

Official Title:

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

ClinicalTrials.gov Link:

http://clinicaltrials.gov/show/NCT00002693

Overall Status:

Completed

Study Phase:

Phase 1

Genders:

Both

Minimum Age:

18 Years

Maximum Age:

N/A

Study Source:

Mayo Clinic

Oversight Authority:

United States: Federal Government

Reasons Why Stopped:

Study Type:

Interventional

Study Design:

Primary Purpose: Treatment

Number of Arms:

0

Number of Groups:

0

Total Enrollment:

0

Enrollment Type:

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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