Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

December 17, 2013 updated by: Leukemia Research Fund

A Randomized Trial for Patients With Acute Myeloid Leukemia or High Risk Myelodysplatic Syndrome Aged 60 or Over

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if stronger doses of chemotherapy given over a longer period of time are as well tolerated or as effective as less intensive chemotherapy.

PURPOSE: This randomized phase III trial is studying intensive regimens of chemotherapy to see how well they work compared to nonintensive regimens of chemotherapy in treating older patients with acute myeloid leukemia or myelodysplastic syndrome.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the response rate, survival, quality of life, and supportive care requirements with intensive versus nonintensive chemotherapy in older patients with acute myeloid leukemia or high risk myelodysplastic syndrome.
  • Compare response achievement, response duration, survival, toxicity and supportive care requirements with differing doses of daunorubicin and cytarabine in these patients receiving intensive chemotherapy.
  • Determine the efficacy of PSC 833 in enhancing the effects of daunorubicin in these patients receiving intensive chemotherapy.
  • Compare relapse rate, deaths in complete remission, disease free survival, and survival with short versus long intensive chemotherapy in these patients.
  • Compare response achievement, response duration, survival, toxicity, quality of life, and resource use with hydroxyurea versus cytarabine in these patients receiving low dose chemotherapy.
  • Determine response achievement, response duration, survival, toxicity, quality of life, and supportive care requirements with the addition of tretinoin to the nonintensive chemotherapy in these patients.
  • Assess the correlation between P-gp and BCL-2 in family members and treatment outcomes and other prognostic factors in these patients with these treatment regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized or electively assigned to either intensive or nonintensive chemotherapy*.

Intensive chemotherapy

  • Induction therapy: Patients are randomized to 1 of 6 treatment arms. Patients receive 2 courses of chemotherapy comprising 1 of 2 daunorubicin doses, 1 of 2 cytarabine doses, thioguanine, and with or without PSC 833.

Patients receive daunorubicin IV once daily on days 1-3 with cytarabine IV twice daily and oral thioguanine once daily on days 1-10 during course 1. Treatment repeats in approximately 31 days as in course 1 except cytarabine and thioguanine are given only on days 1-8.

  • Arm I: Patients receive higher dose of daunorubicin, lower dose of cytarabine, and thioguanine.
  • Arm II: Patients receive higher dose of daunorubicin, higher dose of cytarabine, and thioguanine.
  • Arm III: Patients receive lower dose of daunorubicin, lower dose of cytarabine, and thioguanine.
  • Arm IV: Patients receive lower dose of daunorubicin, higher dose of cytarabine, and thioguanine.
  • Arm V: Patients receive treatment as in arm III in combination with continuous infusion of PSC 833 beginning day 1.
  • Arm VI: Patients receive treatment as in arm IV in combination with continuous infusion of PSC 833 beginning on day 1.

Patients with refractory disease after the first course of induction chemotherapy may continue with the intensive protocol arm or enter the nonintensive arm*. Patients who do not achieve complete remission after completion of induction chemotherapy are removed from study. Patients in complete remission after induction therapy receive consolidation therapy.

  • Consolidation therapy: Patients in complete remission after induction are randomized to either short or long consolidation.

    • Short consolidation: Patients receive mitoxantrone IV on days 1-3 and cytarabine IV over 2 hours twice daily on days 1-3.
    • Long consolidation: Patients complete short consolidation and then receive idarubicin IV over 5 minutes once daily on days 1 and 3, cytarabine IV over 2 hours twice daily and etoposide IV over 1 hour once daily on days 1-3.

Non-intensive chemotherapy*

  • Patients are randomized to 1 of 4 treatment arms.

    • Arm I: Patients receive oral hydroxyurea as necessary to control WBC count until treatment failure.
    • Arm II: Patients receive hydroxyurea as in arm I and oral tretinoin daily for up to 16 weeks.
    • Arm III: Patients receive low dose cytarabine subcutaneously twice daily on days 1-10 every 28 days for a minimum of 4 courses.
    • Arm IV: Patients receive cytarabine as in arm III plus oral tretinoin daily for up to 16 weeks.

NOTE: *Patients with liver function test > 2 times upper limit of normal are not eligible for nonintensive randomization

Quality of life is assessed at study entry, and then at 1, 3, and 6 months.

Patients are followed at one year.

PROJECTED ACCRUAL: Approximately 2,000 patients (1,200 to intensive arm and 800 to nonintensive arm) will be accrued for 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
      • Birmingham, England, United Kingdom, B15 2RR
        • Queen Elizabeth Hospital at University of Birmingham
      • London, England, United Kingdom, WC1E 6AU
        • University College Hospital
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 4XN
        • University Hospital of Wales

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

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Acute myeloid leukemia (de novo or secondary) OR

  • Myelodysplastic syndrome

    • More than 10% myeloblasts in the bone marrow
    • Refractory anemia with excess blasts
    • Refractory anemia with excess blasts in transformation
    • Chronic myelomonocytic leukemia
  • No acute promyelocytic leukemia (FAB type M3)
  • No blastic phase chronic myeloid leukemia

PATIENT CHARACTERISTICS:

Age:

  • 60 and over (younger patients allowed if intensive chemotherapy not indicated)

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • No liver function test ≥ 2 times normal (for non-intensive therapy arm)

Renal:

  • Not specified

Cardiovascular:

  • No myocardial infarction within past 6 months in patients receiving daunorubicin or PSC 833

Other:

  • No other concurrent active malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior cytotoxic 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Survival
Response duration
Response achievement

Secondary Outcome Measures

Outcome Measure
Toxicity by WHO Toxicity Grading after each treatment course
Quality of life EORTC QLQ-C30 at 3 days, 1 month, 3 months, and 6 months from study entry
Resource use (use of blood products, antibiotics and days in hospital) after each treatment course

Collaborators and Investigators

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

Sponsor

Leukemia Research Fund

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

December 1, 1998

Study Completion (Actual)

December 1, 2007

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 18, 2013

Last Update Submitted That Met QC Criteria

December 17, 2013

Last Verified

September 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067831
  • LRF-AML14
  • EU-20016
  • ISRCTN62207270

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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