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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mylotarg Arm | Experimental | 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 |
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| Control Arm | No Intervention | 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gemtuzumab ozogamicin (GO) | Drug |
|
|
| 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 |
| 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 |
End points for treatment-by-covariate interactions are
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Juliette LAMBERT, MD | Versailles Hospital | Principal Investigator |
| Sylvie CASTAIGNE, MD | Versailles Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| C.H.U d'Amiens - Hôpital Sud | Amiens | France | ||||
| Hôpital V. Dupouy |
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| 5 years |
| Argenteuil |
| France |
| CH Avicenne | Bobigny | France |
| CHU Caen | Caen | France |
| HIA Percy | Clamart | 92140 | France |
| Hopital Henri Mondor | Créteil | France |
| CHU Dijon | Dijon | France |
| CH Dunkerque | Dunkirk | France |
| CH Versailles | Le Chesnay | 78157 | France |
| Hôpital Huriez, CHU de Lille | Lille | France |
| CHU Limoges | Limoges | France |
| Hôpital de la Conception | Marseille | 13005 | France |
| Centre Antoine Lacassagne | Nice | 06100 | France |
| CHU d'Orléans | Orléans | 45100 | France |
| Hopital Necker | Paris | France |
| Hopital St Louis | Paris | France |
| Hôpital Saint Antoine | Paris | France |
| CHU Lyon Sud | Pierre-Bénite | France |
| Centre H Becquerel | Rouen | France |
| Institut de Cancérologie de la Loire | Saint-Priest-en-Jarez | 42270 | France |
| IGR | Villejuif | France |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000079982 | Gemtuzumab |
| ID | Term |
|---|---|
| D000080084 | Calicheamicins |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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