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

June 24, 2013 updated by: Memorial Sloan Kettering Cancer Center

A PHASE II STUDY OF MITOXANTRONE AND HIGH-DOSE ARA-C FOLLOWED BY INTENSIVE CONSOLIDATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE FOR MYELOID BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA (CML)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic myelogenous leukemia in blast crisis

    • Bone marrow blasts at least 20% OR
    • Bone marrow blasts plus promyelocytes at least 50%
  • Ineligible for higher priority protocols

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1994

Primary Completion (Actual)

June 1, 2004

Study Completion (Actual)

June 1, 2004

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 25, 2013

Last Update Submitted That Met QC Criteria

June 24, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 94-070
  • CDR0000063832 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-V94-0541

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Leukemia

Clinical Trials on recombinant interferon alfa

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Equatorial Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe