Combination Chemotherapy and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia

NCT ID: NCT00002598

Last Updated: 2013-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1994-06-30
• Study Completion Date: 2004-06-30

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. Interferon alfa may interfere with the growth of cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and interferon alfa in treating patients with chronic myelogenous leukemia.

Detailed Description

OBJECTIVES:

• Determine the effectiveness of induction with high-dose mitoxantrone and cytarabine in patients with chronic myelogenous leukemia (CML) in blast crisis.
• Determine the toxicity and activity of consolidation with high-dose cyclophosphamide and etoposide in these patients.
• Determine the toxicity and activity of maintenance with interferon alfa in these patients.
• Determine the efficacy and tolerability of this regimen in these patients.
• Assess minimal residual disease by cytogenetics, DNA gene rearrangement (Southern blotting), and polymerase chain reaction (PCR) in patients treated with this regimen, and use semiquantitative PCR to evaluate the antileukemic activity of subsequent phases of treatment in patients achieving complete remission.

OUTLINE: Patients are stratified by prior therapy for blast crisis (yes vs no).

• Induction: Patients receive high-dose cytarabine IV over 3 hours on days 1-5 and mitoxantrone IV on day 3. Sargramostim (GM-CSF) is administered subcutaneously (SC) (or IV over 4 hours) daily beginning on day 7 and continuing until blood counts recover. After completion of induction, patients with a suitable HLA-identical bone marrow donor undergo allogeneic bone marrow transplantation according to an appropriate IRB-approved protocol. Patients without a donor proceed to consolidation approximately 4 weeks after hospital discharge following induction.
• Consolidation: Patients receive high-dose cyclophosphamide IV on days 1-4 and etoposide IV continuously on days 5-7. GM-CSF is administered SC (or IV over 4 hours) beginning on day 8 and continuing until blood counts recover. Patients achieving a second chronic phase or complete remission proceed to maintenance approximately 4 weeks after hospital discharge following consolidation.
• Maintenance: Patients receive interferon alfa SC on day 1. Treatment with interferon alfa continues daily in the absence of disease progression or unacceptable toxicity.

Patients with CNS involvement at entry or who develop CNS disease during the study receive CNS therapy as outlined below.

• CNS therapy: Patients undergo whole brain irradiation as soon as possible but not concurrently with mitoxantrone. Patients also receive methotrexate intrathecally 3 times a week until the CSF is clear, weekly for 4 weeks, and then monthly for 6 months.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 4 years.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

recombinant interferon alfa

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2.0 mg/dL

Renal:

• Creatinine less than 2.0 mg/dL

Cardiovascular:

• LVEF greater than 50% by MUGA scan or echocardiogram

Other:

• HIV negative
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Prior therapy for blast crisis allowed

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Mark Adam Weiss, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

CDR0000063832

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-V94-0541

Identifier Type: -

Identifier Source: secondary_id

94-070

Identifier Type: -

Identifier Source: org_study_id