Gemtuzumab Ozogamicin+Cytarabine vs Idarubicin+Cytarabine in Elderly Patients With AML.Mylofrance 4

Study Overview
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Brief Summary
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Purpose : The main objective of this study is to assess the efficacy and tolerance of the addition of repeated doses of low doses (3mg/m2) of Gemtuzumab Ozogamicin (GO) in addition with standard doses of Ara-C in previously untreated patients aged 60 to 80 years with de novo acute myeloblastic leukemia (AML) and non adverse cytogenetics. The main end point for efficacy is 2 years-event free survival. The secondary efficacy endpoints are CR/Cri rates, cumulative incidence of relapse and overall survival. The secondary endpoints for safety are early death rate (before day 30 and 60), grade 3 to 5 adverse events and severe adverse events, cardiac toxicity and quality of life. Additional secondary endpoints are treatment by covariate interactions with respect to biological characteristics present at diagnosis (CD33 positivity, cytogenetic, molecular abnormalities) or after treatment (Minimal residual disease levels). This study is an exploratory study. Patients will be allocated at inclusion with a 2/1 ratio either to receive treatment with GO and cytarabine or Idarubicin and cytarabine in a 3+7 regimen similar to the backbone ALFA 1200 scheme used concurrently by the ALFA group as treatment of AML patients aged >60 years. Primary objective. The primary objective is to assess the efficacy of two doses of Gemtuzumab ozogamicin (GO) during induction and one dose of GO during first consolidation in combination with Cytarabine in elderly patients with AML in the non adverse cytogenetics-risk group.

Official Title
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Etude Exploratoire randomisée Comparant le Traitement Par Gemtuzumab Ozogamicin /Cytarabine au Traitement Standard Par Idarubicine/Cytarabinechez Les Sujets âgés de 60 à 80 Ans et présentant Une LAM et un Caryotype Non défavorable

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Gemtuzumab ozogamicin (GO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a morphologically proven diagnosis AML and both the following criteria: Age ≥ 60 years and < 80 years. Not previously treated for their disease. With favourable or intermediate-risk cytogenetics. (Patients with urgent clinical need to begin treatment might be included before cytogenetic results, when necessary if they do not respond to Hydroxyurea. Patients might be included if the cytogenetic results are not expected in a time limit < 5 days after AML diagnosis). Fit to receive intensive chemotherapy Cardiac function determined by radionucleide or echography within normal limits. Signed informed consent Exclusion Criteria: M3-AML Presence of adverse cytogenetics (according to European LeukemiaNet recommendation.) (17) defined as one of the following abnormalities: -5/5q-, -7, t(6;9), t(v;11q23) excluding t(9;11), inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), complex karyotype (3+ abnormalities) Secondary AML following treatment with radiotherapy or chemotherapy. AML following previously known myeloproliferative or myelodysplastic syndrome. ECOG performance status (PS) 0 to 3 Serum creatinin level > or = 2.5N; AST and ALT level > or = 2.5N; total bilirubin level > or = 2N

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Mylotarg Arm<br>After randomization patients in the experimental arm are assigned to receive chemotherapy with: Gemtuzumab Ozogamicin 3 mg/m2 (maximum dose: 5 mg) per IV, 60mn on Day 1 and 4 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7 | Drug: Gemtuzumab ozogamicin (GO)<br> <br> * Other names: Mylotarg;|
| No Intervention: Control Arm<br>After randomization patients in the control arm are assigned to receive chemotherapy with Idarubicin 12mg/m2 per IV, 30mn on Day 1,2,3 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EFS (defined as the time from randomization to the date of assessment of response if CR or Cri had not been achieved, relapse or death) | Endoint for the primary objective of efficacy is EFS defined as the time from randomization to the date of assessment of response if CR or Cri had not been achieved, relapse or death. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite measure for Efficacy assessed by CR/Cri rates, cumulative incidence of relapse, overall survival. |  | 5 years | 
| Composite measure for safety | incidence of early deaths < day 30 and day 60, grade 3 to 5 adverse events and all serious adverse events during induction and consolidation treatment cardiac toxicity evaluated on cardiac ejection function evaluation by echocardiography or isotopic measure. Quality of life measured by questionaries' EORTC QLQ-C30 repeated at diagnosis, after induction treatment, after the two consolidations and 3 months after the end of treatment. End points for treatment-by-covariate interactions are at diagnosis: percentage of CD33 positivity on blast cells, measured with a standardized method, cytogenetics and most relevant molecular markers (FLT3, MLL, CEBPa, NPM1, DNMT3a., after induction and end of treatment: minimal residual disease determined by WT1 and/or NPM1 transcripts levels. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, untreated, 60-80 years old, favorable and intermediate karyotype