PHASE I STUDY OF CONTINUOUS INFUSION CARBOPLATIN AND TOPOTECAN IN THE TREATMENT OF RELAPSED ACUTE LEUKEMIA AND BLAST CRISIS CHRONIC MYELOGENOUS LEUKEMIA
18 Years
N/A
Both
Leukemia, Neutropenia
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 Clinic | Rochester, Minnesota 55905 |
