A Randomized Phase II Study of Clofarabine / Intermediate-Dose Cytarabine (CLARA)Versus High-Dose Cytarabine (HDAC) as Consolidation in Younger Patients With Newly-Diagnosed Acute Myeloid Leukemia (AML).
Inclusion Criteria at registration:
1. Age 18 years or more and less than 60 years
A morphologically proven diagnosis of AML according to the WHO classification,
cytogenetically (standard karyotype, FISH-MLL) and molecularly (FLT3, CEBPA, NMP1)
3. ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
4. Have adequate renal and hepatic function as indicated by the following laboratory
- 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).
5. Cardiac function determined by radionuclide or echography within normal limits.
6. 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.
7. Must be able and willing to give written informed consent.
8. The subject must be covered by a social security system.
Exclusion Criteria at registration:
1. Patients with AML with favorable risk cytogenetics: M3-AML; CBF-AML including
t(8:21), inv(16), or t(16;16) AML.
2. Ph-positive AML.
3. AML following diagnosed myeloproliferation or patient with prior history of MDS known
for more than 3 months
4. Prior treatment with chemotherapy or radiotherapy for another tumor.
5. Prior tumor, if not stable for at least two years, except in-situ carcinoma and skin
6. Compromised organ function judged to be lifethreatening by the Investigator.
7. Positive serology for HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus) and
HBC (Hepatitis C Virus)(except post vaccination)
8. 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.
9. Other active malignancy.
10. Patients concurrently receiving any other standard or investigational treatment for
their leukemia, with the exception of hydroxyurea.
INCLUSION CRITERIA AT RANDOMIZATION
1. Patients with either in first CR/CRp after the first induction course or in first
CR/CRp after salvage therapy.
2. ECOG performance status 0 to 2.
3. AST and ALT < or = 2.5N; total bilirubin < or = 2N.
4. Creatinine clearance ≥40mL/min (calculated by the cockcroft and Gault method or by
MDRD (see http://nephron.org/cgi-bin/MDRD_GFR/cgi)
5. Patient without HLA identical donor.
EXCLUSION CRITERIA AT RANDOMIZATION
6. 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).
7. Known central nervous system involvement with AML.
8. Uncontrolled active infection of any kind or bleeding.
9. Compromized organ function judged to be lifethreatening by the Investigator.
10. Patient with HLA identical donor identified.