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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT00932412
First received: July 2, 2009
Last updated: April 28, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia
Drug: CLARA
Drug: HDAc
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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).

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • • Safety profile of CLARA versus HDAC consolidation courses [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    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.


  • • Possible predictors to response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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))

  • • MRD (Minimal Residual Disease) level [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    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.

  • • Overall cumulative incidence of relapse [ Time Frame: 120 days ] [ Designated as safety issue: No ]
  • • Overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    OS will be defined as the time from diagnosis to death or last contact with the patient


Estimated Enrollment: 700
Study Start Date: March 2009
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CLARA
Clofarabine / Intermediate-Dose Cytarabine (CLARA) with G-CSF given during each sequence of chemotherapy in order to increase the blast priming.
Drug: CLARA
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00932412

Contacts
Contact: Xavier THOMAS, MD 04 78 86 22 40 ext +33 xavier.thomas@chu-lyon.fr
Contact: Acute Leukemia French Association 01 57 27 67 17 ext +33 alfaleukemia@gmail.com

Locations
France
Hôpital Sud - CHU Amiens Recruiting
Amiens, France, 80054
Principal Investigator: MAROLLEAU Jean Pierre, MD         
Centre Hospitalier Regional et Universitaire d'Angers Recruiting
Angers, France, 49033
Principal Investigator: Norbert IFRAH, MD, Prof         
Hôpital Victor Dupouy Recruiting
Argenteuil, France, 95107
Principal Investigator: SUTTON Laurent, MD         
Hôpital Avicenne - bobigny Recruiting
Bobigny, France, 93009
Principal Investigator: FENAUX Pierre, MD         
Centre Hospitalier Boulogne/Mer Recruiting
Boulogne / Mer, France, 62280
Principal Investigator: Bachra CHOUFI, MD         
Hôpital Clemenceau - chu Caen Recruiting
Caen, France, 14033
Principal Investigator: REMAN Oumédaly, MD         
Centre Hospitalier René Dubos Recruiting
Cergy Pontoise, France, 95303
Principal Investigator: Loic FOUILLARD, MD         
HIA Percy Recruiting
Clamart, France, 92141
Principal Investigator: DE REVEL Thierry, MD         
Hôpital de Corbeil Recruiting
Corbeil, France, 91100
Principal Investigator: DEVIDAS Alain, MD         
Hôpital Mondor Recruiting
Créteil, France, 94010
Principal Investigator: CORDONNIER Catherine, MD         
Hôpital Dubocage Recruiting
Dijon, France, 21000
Principal Investigator: CAILLOT Denis, MD         
Centre Hospitalier Dunkerque Recruiting
Dunkerque, France, 59395
Principal Investigator: BEAUMONT Marie, MD         
Hôpital Michallon Recruiting
Grenoble, France, 38043
Principal Investigator: Jean-Yves CAHN, MD, Prof         
Centre Hospitalier Versailles Recruiting
Le Chesnay, France, 78150
Principal Investigator: CASTAIGNE Sylvie, MD         
Centre Hospitalier Schaffner Recruiting
Lens, France, 62307
Principal Investigator: DUPRIEZ Brigitte, MD         
Hôpital Huriez Recruiting
Lille, France, 59037
Principal Investigator: QUESNEL Bruno, MD         
CHU Dupuytren Recruiting
Limoges, France, 87042
Principal Investigator: BORDESSOULE Dominique, MD         
Institut Paoli-Calmette Not yet recruiting
Marseille, France, 13273
Principal Investigator: Norbert VEY, MD         
Centre Hospitalier Meaux Recruiting
Meaux, France, 77104
Principal Investigator: FRAYFER Jamilé, MD         
CHU - Hôtel Dieu Recruiting
Nantes, France, 44093
Principal Investigator: Jacques DELAUNAY, MD         
Centre A. Lacassagne Recruiting
Nice, France, 06100
Principal Investigator: THYSS Antoine, MD         
Hôpital Archet 1 Recruiting
Nice, France, 06202
Principal Investigator: Lionel MANNONE, MD         
Hôpital St Louis Recruiting
Paris, France, 75010
Contact: CELLI-LEBRAS Karine    01 57 27 67 17 ext +33    karine.celli-lebras@sls.aphp.fr   
Principal Investigator: DOMBRET Hervé, MD         
Paris Necker Recruiting
Paris, France, 75743
Principal Investigator: HERMINE Olivier, MD         
Pitié-Salpetrière Recruiting
Paris, France, 75013
Principal Investigator: DHEDIN Nathalie, MD         
Hôpital Haut Lévêque Recruiting
Pessac, France, 33604
Principal Investigator: Arnaud PIGNEUX, MD         
Hospices Civils de Lyon - Centre Hospitalier Lyon Sud Recruiting
Pierre-benite, France, 69495
Contact: EL HAMRI Mohamed       mohamed.el-hamri@chu-lyon.fr   
Principal Investigator: THOMAS Xavier, MD         
Hôpital V. Provo Recruiting
Roubaix, France, 59056
Principal Investigator: PLANTIER Isabelle, MD         
Centre Henri Becquerel - CHRU ROUEN Recruiting
Rouen, France, 76038
Principal Investigator: Hervé TILLY, MD         
Centre Hospitalier Huguenin Recruiting
Saint Cloud, France, 92210
Principal Investigator: JANVIER Maud, MD         
Hôpital Purpan Recruiting
Toulouse, France, 31059
Principal Investigator: Christian RECHER, MD, Prof         
Sub-Investigator: Francoise HUGUET, MD, Prof         
Centre Hospitalier Valenciennes Recruiting
Valenciennes, France, 59322
Principal Investigator: SIMON Marc, MD         
CHU de Brabois Recruiting
Vandoeuvre Les Nancy, France, 54511
Principal Investigator: Caroline BONMATI, MD         
Institut Gustave Roussy Recruiting
Villejuif, France, 94800
Principal Investigator: DE BOTTON Stéphane, MD         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Xavier THOMAS, MD Hospices Civils de Lyon
  More Information

No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT00932412     History of Changes
Other Study ID Numbers: 2006.456/50
Study First Received: July 2, 2009
Last Updated: April 28, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

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

ClinicalTrials.gov processed this record on November 25, 2014