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For several years, the effective standard induction chemotherapy for AML has been limited to the association of anthracycline and aracytine. GO is the first effective targeted antibody used in leukemia patients. In a previous study, we showed efficacy and safety of fractionated doses of GO used as a single agent for treatment of adult AML patients in first relapse. In the present study the possibility of combining fractionated doses of GO to escalated doses of a 3+7 regimen old is studied in relapsed AML patients > 50 and <70 years.
Induction course are:
GO 3mg/m2 on days 1, 4,7 + the three dose levels were as follows:
level 1: DNR: 45 mg/m2 x 3 days + AraC: 100 mg/m2 x 7 days level 2: DNR: 60 mg/m2 x 3 days + AraC: 100 mg/m2 x 7 days level 3: DNR 60 mg/m2 x 3 days + AraC: 200 mg/m2 x 7 days. with 20 mg of methylprednisolone prior to each GO infusion. Consolidation course: patients in CR may receive 2 additional courses of consolidation chemotherapy with Amsacrine 90 mg/m2 daily for 3 days, and Ara-C (1g/m2/12 hours x 3 days) + GO 3 mg/m2 on day 1.
Treatment with HSCT is offered at the discretion of the physician in charge of the patient. A delay between last infusion of GO and HSCT above 3 months is recommended
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DAUNORUBICINE - ARACYTINE - MYLOTARG - | Experimental | Adaptive Bayesian method for dose-finding in phase I/II clinical trials based on treatment efficacy and toxicity (Thall, Russel, 1998), with successive patients cohorts and three combined dose levels: DNR 45 mg/m2 IV days 1 to 3 + AraC 100 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7. DNR 60 mg/m2 IV days 1 to 3 + AraC 100 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7. DNR 60 mg/m2 IV days 1 to 3 + AraC 200 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7. Two consolidation courses for CR patients: Amsacrine: 90 mg/m2 IV Day 1 Cytarabine: 1g/m2 twice a day IV Days 1 to 4 Mylotarg: 3 mg/m2 IV Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mylotarg | Drug | Dose level study |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting toxicity (DLT) defined by the occurrence of any G3 or G4 non reversible toxicity at day 45 excluding myelosuppression or infection due to neutropenia, and response defined by complete remission at day 45 | Day 45 post first dose of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary endpoint: Duration of second remission in AML patients treated for relapse with chemotherapy + Mylotarg as re-induction and consolidation. | At two years |
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Inclusion Criteria:
Patients with a morphologically proven diagnosis of CD33-positive AML and :
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| CASTAIGNE SYLVIE, PROFESSOR | Acute Leukemia French Association | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Avicenne | Bobigny | France | ||||
| CH |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000079982 | Gemtuzumab |
| ID | Term |
|---|---|
| D000080084 | Calicheamicins |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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| Caen |
| 14033 |
| France |
| Hopital Percy | Clamart | 92141 | France |
| CHU | Créteil | 94010 | France |
| CHU | Lille | 59037 | France |
| CH | Limoges | 87042 | France |
| Hopital Edouard Herriot | Lyon | France |
| CH | Meaux | 77104 | France |
| St Antoine Hospital | Paris | 75012 | France |
| Hopital Saint-Louis | Paris | France |
| CH | Roubaix | 59100 | France |
| CHU | Rouen | 76038 | France |
| CNLCC | Saint-Cloud | France |
| CH | Versailles | France |
| IGR | Villejuif | 94805 | France |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| 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 |