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

NCT ID: NCT00002693

Last Updated: 2011-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-10-31
• Study Completion Date: 2006-04-30

Brief Summary

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.

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.

Conditions

Leukemia; Neutropenia

Study Design

• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

topotecan hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic Cancer Center

Principal Investigators

Scott H. Kaufmann, MD, PhD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: RESULT

Other Identifiers

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

958101

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000064447

Identifier Type: -

Identifier Source: org_study_id