A Randomized Study of Gemtuzumab Ozogamicin (GO) With Daunorubicine and Cytarabine in Untreated Acute Myeloid Leukemia (AML) Aged of 50-70 Years Old

Study Overview
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Brief Summary
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The main objective of this study is to compare conventional chemotherapy: daunorubicin and the Aracytine and this chemotherapy in combination with the monoclonal antibody used Mylotarg in divided doses.

Detailed Description
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Patients with a morphologically proven diagnosis AML and both the two following criteria: Age > 50 years and £ 70 years. Not previously treated for their disease. Randomization will be centralized by phone : Arm A chemotherapy with daunorubicin and Aracytine or Arm B Daunorubicin and Aracytine and Mylotarg.

Official Title
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A Phase III Multicentric Randomized Study of the Combination of Repeated Doses of Gemtuzumab Ozogamicin (GO) With Daunorubicin and Cytarabine Versus Daunorubicin and Cytarabine in Untreated Patients With Acute Myeloid Leukemia (AML) Aged of 50-70 Years Old.

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: conventional chemotherapy (AraC + Daunorubicin),
* Drug: Mylotarg associated with conventional chemotherapy (AraC + Daunorubicin),


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a morphologically proven diagnosis AML and both the two following criteria: Age > 50 years and £ 70 years. Not previously treated for their disease. ECOG performance status 0 to 3 Negative serology HIV, HBV and HBC (except post vaccination) Serum creatinin inf 2.5N; AST and ALT inf 2.5N; total bilirubin inf 2N Cardiac function determined by radionucleide or echography within normal limits. Negative serum pregnancy test within one week before treatment for women of child bearing potential. Signed informed consent. Exclusion Criteria: M3-AML AML following previously know myeloproliferative syndrome. Known central nervous system involvement. Uncontrolled infection Other active malignancy

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A Daunorubicin and Cytarabine<br>Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2. Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4. | Drug: conventional chemotherapy (AraC + Daunorubicin),<br>* Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2. Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4.<br>|
| Experimental: Arm B Daunorubicin and Cytarabine and Mylotarg<br>Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2. Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4. Mylotarg® (GO)induction : 3 mg/m2 IV (2 hours) Days 1, 4, 7. Mylotarg® (GO) First consolidation and Second Consolidation:3 mg/m2 day 1. | Drug: Mylotarg associated with conventional chemotherapy (AraC + Daunorubicin),<br>* Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2. Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4. Mylotarg® (GO)induction : 3 mg/m2 IV (2 hours) Days 1, 4, 7. Mylotarg® (GO) First consolidation and Second Consolidation:3 mg/m2 day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival (EFS) |  | Relapse or death measured from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR rate |  | CR after induction | 
| Cumulative incidence of relapse |  | Relapse from CR | 
| Overall Survival |  | Survival from randomization | 
| Safety of the combination Mylotarg+chemotherapy |  | Duration of study | 
| Possible predictors of response to Mylotarg: with respect to MDR (multi drug resistance) status, cytogenetics risk groups and mutational status (FLT3, MLL, CEBPa, NPM) |  | Duration of study | 
| Relationship between minimal residual disease measured on the expression of WT1 gene and relapse of AML. |  | Duration of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid Leukemia, patient aged 50 to 70 years