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


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia, Neutropenia

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Trial Information

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

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Scott H. Kaufmann, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Federal Government

Study ID:

CDR0000064447

NCT ID:

NCT00002693

Start Date:

October 1995

Completion Date:

April 2006

Related Keywords:

  • Leukemia
  • Neutropenia
  • 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
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Neutropenia

Name

Location

Mayo ClinicRochester, Minnesota  55905