Combination Chemotherapy With or Without Filgrastim and/or Tretinoin in Treating Patients With Acute Myeloid Leukemia

December 18, 2013 updated by: Medical Research Council

Protocol for Patients With High Risk (Resistant, Refractory, Relapsed or Adverse Cytogenetic) AML

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. It is not yet known whether combination chemotherapy with filgrastim and/or tretinoin is more effective than combination chemotherapy alone for acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy with filgrastim and/or tretinoin to see how well they work compared to combination chemotherapy alone in treating patients with acute myeloid leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare standard induction chemotherapy with cytarabine, daunorubicin, and etoposide vs fludarabine and cytarabine in terms of achievement of remission, reasons for remission failure, duration of remission, survival, toxicity, and supportive care needs in patients with high risk acute myeloid leukemia.
  • Determine if the use of filgrastim (G-CSF) or tretinoin administered during and following chemotherapy improves outcome in this patient population.
  • Determine the impact of these treatment regimens on quality of life in these patients.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to type of disease (resistant vs refractory vs relapsed vs adverse cytogenetic), age (under 15 vs 15 to 29, vs 30 to 49 vs 50-59 vs 60-69 vs 70 and over), performance status, and de novo and secondary leukemia. Patients with relapsed disease are further stratified according to duration of first remission (less than 6 months vs 6 to 12 months vs 12 months and over), and prior transplantation (yes vs no).

Patients are randomized into one of two treatment arms for induction chemotherapy.

  • Arm I: Patients receive induction chemotherapy consisting of cytarabine IV every 12 hours on days 1-10, daunorubicin IV on days 1, 3, and 5 and etoposide IV over 1 hour on days 1-5. Patients receive a second course of therapy with cytarabine IV every 12 hours on days 1-8 and daunorubicin and etoposide as in course 1.
  • Arm II: Patients receive 2 courses of induction chemotherapy consisting of fludarabine IV over 30 minutes followed by cytarabine IV over 4 hours on days 1-5.

Patients are further randomized into one of two treatment arms for colony stimulating factor therapy.

  • Arm I: Patients receive filgrastim (G-CSF) subcutaneously or IV daily beginning on day 1 of each course of induction chemotherapy and continuing until blood counts recover, for up to a maximum of 28 days.
  • Arm II: Patients receive no G-CSF during and following induction chemotherapy. Patients are further randomized into one of two treatment arms for retinoid therapy.
  • Arm I: Patients receive oral tretinoin daily beginning on day 1 of induction chemotherapy and continuing for up to a maximum of 90 days.
  • Arm II: Patients receive no retinoid therapy during and following induction chemotherapy.

Following completion of induction chemotherapy, patients achieving complete remission and blood count recovery may receive subsequent therapy consisting of consolidation chemotherapy and/or autologous or allogeneic transplantation.

Quality of life is assessed at 3 months.

PROJECTED ACCRUAL: Approximately 800-1,000 patients will be accrued for this study within 4-5 years.

Study Type

Interventional

Phase

  • Phase 3

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 Kingdom
    • England
      • Birmingham, England, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML) including de novo or secondary AML, or a preexisting myelodysplastic syndrome

    • Overt resistant disease with more than 15% bone marrow blasts after induction course

    • Primary refractory disease

      • Failure to achieve first complete remission after at least 2 induction courses
    • Relapse from first remission with more than 5% bone marrow blasts
    • Complete or partial remission following 1 induction course with adverse cytogenetic abnormalities at diagnosis
  • No acute promyelocytic leukemia
  • No chronic myeloid leukemia in blast transformation
  • No prior relapse from a second or greater remission

PATIENT CHARACTERISTICS:

Age:

  • Any age

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Creatinine clearance at least 30 mL/min

Other:

  • No other active malignancy
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

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
  • Allocation: Randomized

Collaborators and Investigators

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

Sponsor

Medical Research Council

Investigators

  • Study Chair: D. W. Milligan, MD, University Hospital Birmingham NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

August 1, 1998

Study Completion (Actual)

December 1, 2004

Study Registration Dates

First Submitted

June 2, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

December 19, 2013

Last Update Submitted That Met QC Criteria

December 18, 2013

Last Verified

January 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067895
  • MRC-LEUK-AML-HR
  • EU-20008

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.

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