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

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

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 Overview

• Status: Completed
• Conditions: Leukemia; Neutropenia
• Intervention / Treatment: Drug: carboplatin; Biological: filgrastim; Drug: topotecan hydrochloride

Detailed Description

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
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Scott H. Kaufmann, MD, PhD, Mayo Clinic

Publications and helpful links

General Publications

• Kaufmann S, Letendre L, Litzow M, et al.: Phase I study of continuous infusion (CI) topotecan (TPT) and carboplatin (CBDCA) for relapsed or refractory acute leukemia. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A107, 1998.

Study record dates

Study Major Dates

• Study Start: October 1, 1995
• Primary Completion (Actual): April 1, 2006
• Study Completion (Actual): April 1, 2006

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: April 10, 2003
• First Posted (Estimate): April 11, 2003

Study Record Updates

• Last Update Posted (Estimate): August 3, 2011
• Last Update Submitted That Met QC Criteria: August 2, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: neutropenia; recurrent adult acute myeloid leukemia; blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; recurrent adult acute lymphoblastic leukemia; accelerated phase chronic myelogenous leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Agranulocytosis; Leukopenia; Leukocyte Disorders; Leukemia; Leukemia, Myeloid; Neutropenia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Topotecan
• Other Study ID Numbers: CDR0000064447; P30CA015083 (U.S. NIH Grant/Contract); U01CA069912 (U.S. NIH Grant/Contract); 958101 (Other Identifier: Mayo Clinic Cancer Center)