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

This study has been terminated.
Sponsor:
Collaborator:
Assistance Publique - Hôpitaux de Paris
Information provided by:
Acute Leukemia French Association
ClinicalTrials.gov Identifier:
NCT00363025
First received: August 11, 2006
Last updated: February 20, 2008
Last verified: August 2006
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Procedure: Two post-remission strategies
Drug: Idarubicin versus daunorubicin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Acute Leukemia French Association:

Primary Outcome Measures:
  • Overall survival

Secondary Outcome Measures:
  • Complete remission rate
  • Induction death rate

Estimated Enrollment: 465
Study Start Date: November 1999
Estimated Study Completion Date: April 2006
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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00363025

Locations
France
Hopital Avicenne
Bobigny, France
Hopital Percy
Clamart, France
Hopital Henri Mondor
Creteil, France
CHU
Lille, France
CHU
Limoges, France
Hopital Edouard Herriot
Lyon, France
Hopital Saint-Louis
Paris, France
Hopital Pitie-Salpetriere
Paris, France
CNLCC
Rouen, France
CHU
Rouen, France
CNLCC
Saint-Cloud, France
CH
Versailles, France
IGR
Villejuif, France
Sponsors and Collaborators
Acute Leukemia French Association
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Herve Dombret, M.D. Acute Leukemia French Association
  More Information

No publications provided by Acute Leukemia French Association

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00363025     History of Changes
Other Study ID Numbers: ALFA-9803
Study First Received: August 11, 2006
Last Updated: February 20, 2008
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Acute Leukemia French Association:
Acute myeloid leukemia
Older patients
Patient aged 65 years or more

Additional relevant MeSH terms:
Anemia, Refractory, with Excess of Blasts
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Anemia, Refractory
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Daunorubicin
Idarubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014