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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002693
• Other study ID #: CDR0000064447
• Secondary ID: U01CA069912P30CA
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: August 2, 2011
• Start date: October 1995
• Est. completion date: April 2006

Study information

• Verified date: August 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: April 2006
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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:

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Biological:
• filgrastim

Drug:
• carboplatin

• topotecan hydrochloride

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.