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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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).

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Procedure: Two post-remission strategies
* Drug: Idarubicin versus daunorubicin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Two post-remission strategies|nan|
|Drug: Idarubicin versus daunorubicin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate |  |  | 
| Induction death rate |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukemia, Older patients, Patient aged 65 years or more