DNR and AraC Combined to Fractionated Mylotarg® in Patients With First Relapse of AML (MYLOFRANCE2)

Acute Leukemia French Association

Status and phase: Completed; Phase 2; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Mylotarg

Study type: Interventional

Funder types: Other

Identifiers

NCT02182596

MYLOFRANCE 2

Details and patient eligibility

About

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.

Full description

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

Enrollment: 20 patients

Sex: All

Ages: 50 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients with a morphologically proven diagnosis of CD33-positive AML and :

1. Age ≥ 50 years and ≤ 70 years.
2. First relapsing AML with a duration of first CR ≥ 3 and ≤18 months
3. ECOG performance status 0 to 3
4. Negative serology HIV, HBV and HBC (except post vaccination)
5. Serum creatinine ≤ 2N; AST and ALT ≤ 2N; total bilirubin ≤ 2N
6. Cardiac function determined by radionuclide or echography within normal limits.
7. Negative serum pregnancy test within one week before treatment for women of child bearing potential
8. Signed informed consent.

Exclusion criteria

1. M3-AML
2. AML following diagnosed myelodysplastic syndrome or myeloproliferation
3. Known central nervous system involvement with AML
4. Prior treatment with HSCT.
5. Previous treatment with Anti CD33 antibodies
6. Uncontrolled infection
7. Other active malignancy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

DAUNORUBICINE - ARACYTINE - MYLOTARG -

Experimental group

Description:

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.

Treatment:

Drug: Mylotarg