DNR and AraC Combined to Fractionated Mylotarg® in Patients With First Relapse of AML

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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A Dose-finding Phase I/II Trial of Daunorubicin and Cytarabine Combined to Fractionated Mylotarg® as Re-induction Treatment in Patients With First Relapse of Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Mylotarg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a morphologically proven diagnosis of CD33-positive AML and : Age ≥ 50 years and ≤ 70 years. First relapsing AML with a duration of first CR ≥ 3 and ≤18 months ECOG performance status 0 to 3 Negative serology HIV, HBV and HBC (except post vaccination) Serum creatinine ≤ 2N; AST and ALT ≤ 2N; total bilirubin ≤ 2N Cardiac function determined by radionuclide 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 diagnosed myelodysplastic syndrome or myeloproliferation Known central nervous system involvement with AML Prior treatment with HSCT. Previous treatment with Anti CD33 antibodies 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAUNORUBICINE - ARACYTINE - MYLOTARG -<br>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. | Drug: Mylotarg<br>* Dose level study<br>* Other names: Gemtuzumab Ozogamicin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, First relapsing AML