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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00932412
Recruitment Status : Completed
First Posted : July 3, 2009
Last Update Posted : September 21, 2016
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

This study is a phase II randomized multicenter study. Patients will be enrolled at time of diagnosis and will receive one or two cycles of induction chemotherapy. Patients, without indication of intensification by allogeneic stem cell transplantation and/or without HLA (Human Leukocyte Antigen)-compatible donor, who attain a CR after one or two cycles of induction chemotherapy, will be eligible for the study Clofarabine / Intermediate-Dose Cytarabine (CLARA)versus High-Dose Cytarabine (HDAC)and will be randomized between 3 courses of CLARA chemotherapy and 3 courses of HDAC chemotherapy as consolidation.

We will compare efficacy and toxicity among the two arms.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: CLARA Drug: HDAc Phase 2

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 735 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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).
Study Start Date : March 2009
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016

Arm Intervention/treatment
Experimental: CLARA
Clofarabine / Intermediate-Dose Cytarabine (CLARA) with G-CSF given during each sequence of chemotherapy in order to increase the blast priming.
Clofarabine 30 mg/m2/day IV (2h) on days 2 to 6 (administered as a 2h infusion in 250 ml of 0.9% normal saline solution) Cytarabine 1 g/m2/day intravenous (2h) 4 hours later on days 1 to 5 (administered as a 2h infusion in 250 ml of 5% dextrose in water) G-CSF 5 microg/kg/day intravenous from day 1 to day 6 (administered as a 30 mn infusion in 20 ml of dextrose 5% in water)

Active Comparator: HDAC
High-Dose Cytarabine (HDAC) with G-CSF given during each sequence of chemotherapy in order to increase the blast priming.
Drug: HDAc
Cytarabine 3 g/m2/12h intravenous (3h) on days 1, 3, 5 (administered as a 3h infusion in 250 ml of 5% dextrose in water) G-CSF 5 microg/kg/day intravenous from day 1 to day 5 (administered as a 30 mn infusion in 20 ml of dextrose 5% in water)

Primary Outcome Measures :
  1. 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. [ Time Frame: 2 years ]
    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: 1) to exclude patients with an identified donor; 2) to adjust Relapse Free survival (RFS) comparison on the interaction with stem cell transplantation in first remission; and 3) to censure at transplant time the patients allografted before disease progression after randomization (late donor identification) as sensitivity analysis.

Secondary Outcome Measures :
  1. • Safety profile of CLARA versus HDAC consolidation courses [ Time Frame: 2 years ]

    All toxicity encountered during therapy will be evaluated according to the CTC expanded Common Toxicity Criteria and causal relationship to investigational products will be reported.

    Serious Adverse Events encountered 3 MONTHS after the last cycle of study chemotherapy (induction/salvage/CLARA/HDAC), whether or not ascribed to the study, will be recorded in the Serious Adverse Event form.

  2. • Possible predictors to response [ Time Frame: 2 years ]
    Possible predictors to response: with respect to cytogenetics risk groups and mutational status: FLT3 (Fms-like tyrosine kinase 3), MLL (myeloid/ lymphoid or mixed-lineage leukemia), CEBPA (CCAAT / enhancer binding protein α) and NPM(Nucleophosmin))

  3. • MRD (Minimal Residual Disease) level [ Time Frame: 2 years ]

    Evaluation of MRD in patients with AML in clinical remission is a potentially useful tool for assessing the risk of relapse and guiding further therapeutic decisions. Once an aberrant pattern is identified at diagnosis, it will serve as a "patient-specific probe" to be used, with standard triple/quadruple labelling, to track residual disease longitudinally. Bone marrow and peripheral blood samples for MRD evaluation will be collected at fixed time points:

    • End of induction in patients achieving CR/CRp.
    • End of consolidation 3.
    • Every 6 months during follow-up for 2 years.

  4. • Overall cumulative incidence of relapse [ Time Frame: 120 days ]
  5. • Overall survival (OS) [ Time Frame: 2 years ]
    OS will be defined as the time from diagnosis to death or last contact with the patient

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


  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
  5. Patient without HLA identical donor.


  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00932412

Hôpital Sud - CHU Amiens
Amiens, France, 80054
Centre Hospitalier Regional et Universitaire d'Angers
Angers, France, 49033
Hôpital Victor Dupouy
Argenteuil, France, 95107
Hôpital Avicenne - bobigny
Bobigny, France, 93009
Centre Hospitalier Boulogne/Mer
Boulogne / Mer, France, 62280
Hôpital Clemenceau - chu Caen
Caen, France, 14033
Centre Hospitalier René Dubos
Cergy Pontoise, France, 95303
HIA Percy
Clamart, France, 92141
Hôpital de Corbeil
Corbeil, France, 91100
Hôpital Mondor
Créteil, France, 94010
Hôpital Dubocage
Dijon, France, 21000
Centre Hospitalier Dunkerque
Dunkerque, France, 59395
Hôpital Michallon
Grenoble, France, 38043
Centre Hospitalier Versailles
Le Chesnay, France, 78150
Centre Hospitalier Schaffner
Lens, France, 62307
Hôpital Huriez
Lille, France, 59037
CHU Dupuytren
Limoges, France, 87042
Institut Paoli-Calmette
Marseille, France, 13273
Centre Hospitalier Meaux
Meaux, France, 77104
CHU - Hôtel Dieu
Nantes, France, 44093
Centre A. Lacassagne
Nice, France, 06100
Hôpital Archet 1
Nice, France, 06202
Hôpital St Louis
Paris, France, 75010
Paris, France, 75013
Paris Necker
Paris, France, 75743
Hôpital Haut Lévêque
Pessac, France, 33604
Hospices Civils de Lyon - Centre Hospitalier Lyon Sud
Pierre-benite, France, 69495
Hôpital V. Provo
Roubaix, France, 59056
Centre Henri Becquerel - CHRU ROUEN
Rouen, France, 76038
Centre Hospitalier Huguenin
Saint Cloud, France, 92210
Hôpital Purpan
Toulouse, France, 31059
Centre Hospitalier Valenciennes
Valenciennes, France, 59322
CHU de Brabois
Vandoeuvre Les Nancy, France, 54511
Institut Gustave Roussy
Villejuif, France, 94800
Sponsors and Collaborators
Hospices Civils de Lyon
Principal Investigator: Xavier THOMAS, MD Hospices Civils de Lyon

Responsible Party: Hospices Civils de Lyon Identifier: NCT00932412     History of Changes
Other Study ID Numbers: 2006.456/50
First Posted: July 3, 2009    Key Record Dates
Last Update Posted: September 21, 2016
Last Verified: September 2016

Keywords provided by Hospices Civils de Lyon:
Younger Patients with Newly-Diagnosed Acute Myeloid Leukemia (AML).

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs