The CLARA Study From the Acute Leukemia French Association (ALFA 0702 Trial)

Because of the results of our former trial (ALFA-9802) [Thomas, 2005], chemotherapy will be combined in each arm with G-CSF (Granulocyte Colony-Stimulating Factor) given during each sequence of chemotherapy in order to increase the blast priming.

Inclusion criteria

at registration:

• Age 18 years or more and less than 60 years
• With:

A morphologically proven diagnosis of AML according to the WHO classification, cytogenetically (standard karyotype, FISH-MLL) and molecularly (FLT3, CEBPA, NMP1) defined.

• ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
• Have adequate renal and hepatic function as indicated by the following laboratory values:

• Creatinine clearance (calculated by the cockcroft and Gault method) ≥ 40mL/min;
• AST (Aspartate amino transférase) and ALT (Alanine Amino Transférase ) < or = 2.5N; total bilirubin < or = 2N (unless related to the underlying disease).
• Cardiac function determined by radionuclide or echography within normal limits.
• Women of child-bearing potential (i.e. women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods, and must have a negative serum or urine pregnancy test within 2 weeks prior the beginning treatment on this trial.
• Must be able and willing to give written informed consent.
• The subject must be covered by a social security system.

Exclusion criteria

at registration:

• Patients with AML with favorable risk cytogenetics: M3-AML; CBF-AML including t(8:21), inv(16), or t(16;16) AML.
• Ph-positive AML.
• AML following diagnosed myeloproliferation or patient with prior history of MDS known for more than 3 months
• Prior treatment with chemotherapy or radiotherapy for another tumor.
• Prior tumor, if not stable for at least two years, except in-situ carcinoma and skin carcinoma
• Compromised organ function judged to be lifethreatening by the Investigator.
• Positive serology for HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus) and HBC (Hepatitis C Virus)(except post vaccination)
• Uncontrolled active infection of any kind or bleeding. Patients with infections who are under active treatment with antibiotics and whose infections are controlled may be entered to the study.
• Other active malignancy.
• Patients concurrently receiving any other standard or investigational treatment for their leukemia, with the exception of hydroxyurea.

Inclusion criteria

AT RANDOMIZATION

• Patients with either in first CR/CRp after the first induction course or in first CR/CRp after salvage therapy.
• ECOG performance status 0 to 2.
• AST and ALT < or = 2.5N; total bilirubin < or = 2N.
• Creatinine clearance ≥40mL/min (calculated by the cockcroft and Gault method or by MDRD (see http://nephron.org/cgi-bin/MDRD_GFR/cgi)
• Patient without HLA identical donor.

Exclusion criteria

AT RANDOMIZATION

• Patients belonging to the intermediate 1 risk group (CEBPA+ or NPM1+ without Flt3-ITD) in CR/CRp after the first induction course. These patients will go out of the study and receive consolidation cycles based on HD-AraC (Aracytine).
• Known central nervous system involvement with AML.
• Uncontrolled active infection of any kind or bleeding.
• Compromized organ function judged to be lifethreatening by the Investigator.
• Patient with HLA identical donor identified.