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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00002693
First received: November 1, 1999
Last updated: August 2, 2011
Last verified: August 2011
  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.


Condition Intervention Phase
Leukemia
Neutropenia
Biological: filgrastim
Drug: carboplatin
Drug: topotecan hydrochloride
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: PHASE I STUDY OF CONTINUOUS INFUSION CARBOPLATIN AND TOPOTECAN IN THE TREATMENT OF RELAPSED ACUTE LEUKEMIA AND BLAST CRISIS CHRONIC MYELOGENOUS LEUKEMIA

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Study Start Date: October 1995
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002693

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Scott H. Kaufmann, MD, PhD Mayo Clinic
  More Information

Additional Information:
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.

Responsible Party: Scott Harold Kaufmann, M.D. Ph.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00002693     History of Changes
Other Study ID Numbers: CDR0000064447, U01CA069912, P30CA015083, 958101
Study First Received: November 1, 1999
Last Updated: August 2, 2011
Health Authority: United States: Federal Government

Keywords provided by Mayo Clinic:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neutropenia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Carboplatin
Topotecan
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014