Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia

December 3, 2013 updated by: Medical Research Council

Medical Research Council Working Party on Leukaemia in Childhood Acute Myeloid Leukaemia Trial 12

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow doctors to give higher doses of chemotherapy and kill more cancer cells. It is not yet known whether chemotherapy is more effective with or without bone marrow transplantation for acute myeloid leukemia.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without bone marrow transplantation in treating children who have acute myeloid leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare two induction schedules with respect to achievement and duration of remission, survival, toxicity, and supportive care requirements in children with previously untreated acute myeloid leukemia.
  • Compare 4 versus 5 courses of treatment in total (where the final course is either chemotherapy or bone marrow transplantation) with respect to remission duration, relapse rates, deaths in remission, and overall survival in these patients.
  • Compare the value of allogeneic bone marrow transplantation versus conventional chemotherapy with respect to remission duration, relapse rates, deaths in remission, and overall survival in these patients.
  • Reduce toxicity without compromising survival by restricting the number of patients receiving bone marrow transplant in this study.

OUTLINE: This is a randomized study. Patients are first randomized to one of two induction treatment arms.

  • Induction Arm I: Patients receive 2 courses of cytarabine IV push every 12 hours on days 1-10 or 1-8 (20 or 16 doses); daunorubicin IV over 6 hours on days 1, 3, and 5; and etoposide IV over 4 hours on days 1-5 (5 doses).
  • Induction Arm II: Patients receive 2 courses of mitoxantrone IV over 6 hours on days 1, 3, and 5; cytarabine IV push every 12 hours on days 1-10 or 1-8 (20 or 16 doses); and etoposide IV over 4 hours on days 1-5 (5 doses).

Patients with no CNS disease at diagnosis receive 3 courses of triple intrathecal therapy (methotrexate, cytarabine, and hydrocortisone), one after each of the first 3 courses of chemotherapy. Patients with CNS disease receive at least 6 courses of intrathecal therapy (2 courses per week), then monthly courses until the final course of chemotherapy is complete.

Patients in complete response after induction course 2 continue on this study. Patients not in complete response after induction course 2 are taken off study and are eligible for the current Medical Research Council (MRC) refractory/relapse study or another therapy.

Course 3: All patients continuing on this study receive amsacrine IV over 1 hour daily on days 1-5, cytarabine continuous IV infusion daily on days 1-5, and etoposide IV over 4 hours on days 1-5 as course 3. After course 3, patients are assigned to two risk groups: good risk patients, and standard and poor risk patients.

Standard and poor risk patients with no matched sibling donor and good risk patients are then further randomized to consolidation in arms I or II.

  • Arm I: Patients receive mitoxantrone IV over 6 hours on days 1-5 and cytarabine IV over 2 hours every 12 hours on days 1-3 (4 courses of chemotherapy total).
  • Arm II: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, and asparaginase subcutaneous infusion 3 hours after completion of the last cytarabine doses on days 2 and 9, followed by a course of mitoxantrone and cytarabine as in arm I (5 courses of chemotherapy total).

Standard and poor risk children with matched sibling donor are randomized to arms III or IV.

  • Arm III: Patients receive no consolidation treatment (3 courses of chemotherapy total) plus bone marrow transplantation.
  • Arm IV: Patients receive cytarabine and asparaginase as in arm II (4 courses of chemotherapy total) plus bone marrow transplantation.

Patients are followed for at least 1 year.

PROJECTED ACCRUAL: Approximately 2,000 patients will be accrued into this study over 5 years.

Study Type

Interventional

Enrollment (Anticipated)

2000

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
      • Manchester, England, United Kingdom, M20 4BX
        • Christie Hospital N.H.S. Trust

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

No older than 15 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Histologically confirmed de novo or secondary acute myeloid leukemia (AML)
    • Aggressive myelodysplastic syndromes (refractory anemia with excess blasts (RAEB) and RAEB in transformation) for which intensive AML therapy is considered appropriate
    • Acute promyelocytic leukemia (should also be entered into protocol MRC-ATRA)
  • No chronic myeloid leukemia in blast transformation
  • Must be considered suitable for intensive chemotherapy

PATIENT CHARACTERISTICS:

Age:

  • Under 16

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Not specified

Other:

  • No other concurrent active malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy for leukemia

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: Tim O.B. Eden, MB, BS, FRCPE, FRCP, FRCPCH, F, The Christie 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

July 1, 1998

Study Completion (ACTUAL)

December 1, 2005

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

April 29, 2003

First Posted (ESTIMATE)

April 30, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

December 4, 2013

Last Update Submitted That Met QC Criteria

December 3, 2013

Last Verified

December 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000066463
  • MRC-LEUK-AML12CH
  • EU-98010

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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