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

NCT00932412 | Completed Phase 2 DMC

• 2 other identifiers: 2006.456/502008-000668-18
• Study Type: interventional
• Target: 735
• Locations: 1 country
• Sites: 34

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.

Conditions

Acute Myeloid Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (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.

  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.

  2 years

Secondary Outcomes (5)

• • Safety profile of CLARA versus HDAC consolidation courses

  2 years

• • Possible predictors to response

  2 years

• • MRD (Minimal Residual Disease) level

  2 years

• • Overall cumulative incidence of relapse

  120 days

• • Overall survival (OS)

  2 years

Study Arms (2)

CLARA

EXPERIMENTAL

Clofarabine / Intermediate-Dose Cytarabine (CLARA) with G-CSF given during each sequence of chemotherapy in order to increase the blast priming.

Drug: CLARA

HDAC

ACTIVE COMPARATOR

High-Dose Cytarabine (HDAC) with G-CSF given during each sequence of chemotherapy in order to increase the blast priming.

Drug: HDAc

Interventions

CLARA DRUG

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)

CLARA

HDAc DRUG

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)

HDAC

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (34)

Hôpital Sud - CHU Amiens

Amiens, 80054, France

Location

Centre Hospitalier Regional et Universitaire d'Angers

Angers, 49033, France

Location

Hôpital Victor Dupouy

Argenteuil, 95107, France

Location

Hôpital Avicenne - bobigny

Bobigny, 93009, France

Location

Centre Hospitalier Boulogne/Mer

Boulogne-sur-Mer, 62280, France

Location

Hôpital Clemenceau - chu Caen

Caen, 14033, France

Location

Centre Hospitalier René Dubos

Cergy-Pontoise, 95303, France

Location

HIA Percy

Clamart, 92141, France

Location

Hôpital de Corbeil

Corbeil, 91100, France

Location

Hôpital Mondor

Créteil, 94010, France

Location

Hôpital Dubocage

Dijon, 21000, France

Location

Centre Hospitalier Dunkerque

Dunkirk, 59395, France

Location

Hôpital Michallon

Grenoble, 38043, France

Location

Centre Hospitalier Versailles

Le Chesnay, 78150, France

Location

Centre Hospitalier Schaffner

Lens, 62307, France

Location

Hôpital Huriez

Lille, 59037, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

Institut Paoli-Calmette

Marseille, 13273, France

Location

Centre Hospitalier Meaux

Meaux, 77104, France

Location

CHU - Hôtel Dieu

Nantes, 44093, France

Location

Centre A. Lacassagne

Nice, 06100, France

Location

Hôpital Archet 1

Nice, 06202, France

Location

Hôpital St Louis

Paris, 75010, France

Location

Pitié-Salpetrière

Paris, 75013, France

Location

Paris Necker

Paris, 75743, France

Location

Hôpital Haut Lévêque

Pessac, 33604, France

Location

Hospices Civils de Lyon - Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Hôpital V. Provo

Roubaix, 59056, France

Location

Centre Henri Becquerel - CHRU ROUEN

Rouen, 76038, France

Location

Centre Hospitalier Huguenin

Saint-Cloud, 92210, France

Location

Hôpital Purpan

Toulouse, 31059, France

Location

Centre Hospitalier Valenciennes

Valenciennes, 59322, France

Location

CHU de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Related Publications (3)

• Fenwarth L, Thomas X, de Botton S, Duployez N, Bourhis JH, Lesieur A, Fortin G, Meslin PA, Yakoub-Agha I, Sujobert P, Dumas PY, Recher C, Lebon D, Berthon C, Michallet M, Pigneux A, Nguyen S, Chantepie S, Vey N, Raffoux E, Celli-Lebras K, Gardin C, Lambert J, Malfuson JV, Caillot D, Maury S, Ducourneau B, Turlure P, Lemasle E, Pautas C, Chevret S, Terre C, Boissel N, Socie G, Dombret H, Preudhomme C, Itzykson R. A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia. Blood. 2021 Jan 28;137(4):524-532. doi: 10.1182/blood.2020005524.

  PMID: 32871585 BACKGROUND

• Hirsch P, Lambert J, Bucci M, Deswarte C, Boudry A, Lambert J, Fenwarth L, Micol JB, Terre C, Celli-Lebras K, Thomas X, Dombret H, Duployez N, Preudhomme C, Itzykson R, Delhommeau F. Multi-target measurable residual disease assessed by error-corrected sequencing in patients with acute myeloid leukemia: An ALFA study. Blood Cancer J. 2024 Jun 13;14(1):97. doi: 10.1038/s41408-024-01078-8.

  PMID: 38871702 BACKGROUND

• Michallet M, Sobh M, Morisset S, Deloire A, Raffoux E, de Botton S, Caillot D, Chantepie S, Girault S, Berthon C, Bertoli S, Lepretre S, Leguay T, Castaigne S, Marolleau JP, Pautas C, Malfuson JV, Veyn N, Braun T, Gastaud L, Suarez F, Schmidt A, Gressin R, Bonmati C, Celli-Lebras K, El-Hamri M, Ribaud P, Dombret H, Thomas X, Bergeron A. Antifungal Prophylaxis in AML Patients Receiving Intensive Induction Chemotherapy: A Prospective Observational Study From the Acute Leukaemia French Association (ALFA) Group. Clin Lymphoma Myeloma Leuk. 2022 May;22(5):311-318. doi: 10.1016/j.clml.2021.10.011. Epub 2021 Oct 25.

  PMID: 34895843 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Xavier THOMAS, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2009
• First Posted: July 3, 2009
• Study Start: March 1, 2009
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 27, 2026

Record last verified: 2026-05

Locations

FR (34)