A Randomized Study of Post-Remission Therapy in Elderly Patients With Acute Myelogenous Leukemia.

February 20, 2008 updated by: Acute Leukemia French Association

A Randomized Multicenter Study of More Intensive Versus Less Intensive Post-Remission Therapy in Elderly Patients With Acute Myelogenous Leukemia (AML) or Transformed Refractory Anemia With Excess Blasts (RAEB-t).

In this ALFA-9803 trial in AML patients aged 65 years or more, we randomly compared idarubicin or daunorubicin throughout the study (first randomization) and two different post-remission strategies (second randomization): one single intensive consolidation course similar to induction versus six ambulatory cycles with one dose of idarubicin/daunorubicin (day 1) and 2x60 mg/m2/d cytarabine SC (day 1 to 5) delivered in out-patients on a monthly basis. Primary endpoint was 2-year overall survival (OS). Study hypotheses were equivalence for the idarubicin/daunorubicin comparison and a 15% difference in 2-year OS for the post-remission therapy comparison.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Patients were randomized at baseline (first R1 randomization) to receive either daunorubicin (DNR) or idarubicin (IDA) as an anthracycline for induction and post-remission therapy. This first randomization was stratified on centers and AML type (de novo versus post-MDS AML). Induction chemotherapy consisted of a 4+7 course with either DNR at a daily dosage of 45 mg/m2 or IDA at a daily dosage of 9 mg/m2 for four days (day 1 to day 4) in combination with 200 mg/m2 cytarabine per day as a continuous IV infusion for seven days (day 1 to 7). Lenograstim granulocyte colony-stimulating factor (G-CSF) was administered in all patients from day 9 until myeloid recovery (3 consecutive days with PMN more than 1.0 G/L) by IV infusion and at a daily dosage of 263 microg/day for a maximum of 28 days. A blood and marrow aspiration smear examination was performed at day 21. A salvage course of chemotherapy may be offered to patients with persistent leukemia (defined below), but only if they did not present acquired contra-indication to further intensive chemotherapy (baseline criteria). Salvage consisted of six 1-hour IV bolus of intermediate-dose cytarabine (500 mg/m2/12h day 1 to 3) combined to mitoxantrone (MTZ) at a daily dosage of 12 mg/m2 for two days (day 3 and 4). G-CSF administration was stopped before salvage onset and restarted from day 5 of the salvage course until myeloid recovery for a maximum of 28 days.

Patients reaching complete remission (CR) after induction or induction followed by salvage were eligible for a second R2 randomization between mild versus intensive post-remission therapy, but only if they did not present acquired contra-indication to further intensive chemotherapy (baseline criteria). This second randomization was stratified on centers, AML groups (de novo versus post-MDS AML), and first randomization groups. Mild post-remission therapy was administered in out-patients and consisted of six 1+5 monthly courses with either 45 mg/m2 DNR or 9 mg/m2 IDA for one day (day 1) in combination with 60 mg/m2/12h cytarabine as a SC infusion for five days (day 1 to 5). No G-CSF support was given after these six courses. Intensive post-remission therapy required another hospitalization and was a repetition of the first 4+7 induction administered at the same doses and followed by G-CSF administration as well.

Study Type

Interventional

Enrollment

465

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

  • France
      • Bobigny, France
        • Hopital Avicenne
      • Clamart, France
        • Hôpital Percy
      • Creteil, France
        • Hôpital Henri Mondor
      • Lille, France
        • CHU
      • Limoges, France
        • CHU
      • Lyon, France
        • Hôpital Edouard Herriot
      • Paris, France
        • Hôpital Pitié-Salpêtrière
      • Paris, France
        • Hôpital Saint-Louis
      • Rouen, France
        • CHU
      • Rouen, France
        • CNLCC
      • Saint-Cloud, France
        • CNLCC
      • Versailles, France
        • CH
      • Villejuif, France
        • IGR

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

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Male or female aged 65 years or more. Patient with previously untreated AML except M3 in the FAB classification. Patient with previously untreated transformed refractory anemia with excess blasts (RAEB-t).

Patients with AML secondary to a previously untreated myelodysplastic syndrome (MDS), documented or not, are eligible, as well as those with RAEB-t evolving from a previous known MDS.

Patients with a Performance Status < 3. Patient who has given his/her written informed consent.

Exclusion Criteria:

Patients with AML3 in the FAB classification. Patients with blast crisis of previously known myeloproliferative syndrome. Patients with AML secondary to previous treatment with cytotoxic chemotherapy or radiotherapy (therapy-related AML).

Patients with another concommitant neoplasia. Patients with leukemic central nervous system involvement. Patients with a Grade > 2 uncontrolled infection. Patients with Grade > 2 visceral contra-indications to treatment with induction chemotherapy (except if leukemia-related).

Bilirubin > 2 times the normal range of the laboratory. Serum creatinine > 2 times the normal range of the laboratory. Patients with cardiac contra-indication to treatment with anthracyclines.

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
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival

Secondary Outcome Measures

Outcome Measure
Complete remission rate
Induction death rate

Collaborators and Investigators

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

Sponsor

Acute Leukemia French Association

Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Herve Dombret, M.D., Acute Leukemia French Association

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

November 1, 1999

Study Completion

April 1, 2006

Study Registration Dates

First Submitted

August 11, 2006

First Submitted That Met QC Criteria

August 11, 2006

First Posted (Estimate)

August 15, 2006

Study Record Updates

Last Update Posted (Estimate)

February 21, 2008

Last Update Submitted That Met QC Criteria

February 20, 2008

Last Verified

August 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALFA-9803

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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