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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).


Phase 2
18 Years
60 Years
Open (Enrolling)
Both
Acute Myeloid Leukemia

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Trial Information

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).


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


Inclusion Criteria at registration:

1. Age 18 years or more and less than 60 years

2. With:

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

3. ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.

4. 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).

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
carcinoma

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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

DFS (disease free survival) following first remission achievement (CR : Complete Remission or CRp : Complete Remission but platelet count < 100 x109/L) in younger patients with intermediate-risk or unfavorable-risk AML.

Outcome Description:

As all these patients are eligible for allogenic stem cell transplantation in first remission if they have a donor and the comparison of interest primarily concerns non-transplanted patients, it is planned to exclude patients with an identified donor, and to censure at transplant time the patients allografted before disease progression after randomization (late donor identification) for the comparison.

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Xavier THOMAS, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hospices Civils de Lyon

Authority:

France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:

2006.456/50

NCT ID:

NCT00932412

Start Date:

March 2009

Completion Date:

September 2015

Related Keywords:

  • Acute Myeloid Leukemia
  • Younger Patients with Newly-Diagnosed Acute Myeloid Leukemia (AML).
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

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