Clinical trial NCT02182596: DNR and AraC Combined to Fractionated Mylotarg® in Patients With First Relapse of AML
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
First relapsing AML
Lead sponsor: Acute Leukemia French Association
Sponsor class: OTHER
First posted: 2014-07-08
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 45 post first dose of treatment
Secondary outcomes:
measure: Secondary endpoint: Duration of second remission in AML patients treated for relapse with chemotherapy + Mylotarg as re-induction and consolidation.
timeFrame: At two years
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hopital Avicenne
city: Caen
country: France
facility: CH
city: Clamart
country: France
facility: Hopital Percy
city: Creteil
country: France
facility: CHU
city: Lille
country: France
facility: CHU
city: Limoges
country: France
facility: CH
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Meaux
country: France
facility: CH
city: Paris
country: France
facility: St Antoine Hospital
city: Paris
country: France
facility: Hopital Saint-Louis
city: Roubaix
country: France
facility: CH
city: Rouen
country: France
facility: CHU
city: Saint-Cloud
country: France
facility: CNLCC
city: Versailles
country: France
facility: CH
city: Villejuif
country: France
facility: IGR
Study officials:
affiliation: Acute Leukemia French Association
name: CASTAIGNE SYLVIE, PROFESSOR
role: PRINCIPAL_INVESTIGATOR
References: