Clofarabine/Ara-C Treatment Combined With Reduced-intensity Conditioning Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Primary Treatment Failure (setric)

The present trial will establish a prospective sequential Allogeneic Stem Cell Transplantation (allo-SCT) treatment combining both salvage chemotherapy and Reduced Intensity Conditioning (RIC) for primary treatment failure Acute Myeloid Leukemia (AML), to which future innovative strategies can be compared.

Study Overview

• Status: Completed
• Conditions: AML
• Intervention / Treatment: Drug: Clofarabine

Detailed Description

Primary Endpoint: To improve the 2 year overall survival in patients with primary treatment failure

* Secondary Endpoints:

• Feasibility of early transplantation within a multicenter trial
• Leukemia-free survival (LFS) at 2 years from transplantation
• Leukemia Response rate at day +30, +90 and 6 months
• Cumulative incidence of relapse, death from leukemia, and non-relapse mortality (NRM)
• Incidence and severity of acute and chronic Graft-versus-Host disease
• Feasibility and safety of early discontinuation of immunosuppressive therapy

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • CHU de Bordeaux
  • Caen, France
    • CHU CAEN
  • Lille, France
    • CHRU Lille
  • Lyon, France
    • Hôpital Edouard Herriot
  • Marseille, France
    • Institut Paoli Calmette
  • Nantes, France, 44200
    • Nantes University Hospital
  • Paris, France
    • Paris Saint Louis
  • Strasbourg, France
    • CHRU de Strasbourg
  • Toulouse, France
    • Chu Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of AML in the status of primary induction failure (i.e. persistent leukemia after 2 courses of induction chemotherapy or persisting bone marrow hypoplasia fol-lowing induction chemotherapy +/-minimal residual disease)
• Age: 18-55 years
• Availability of an HLA identical family donor OR unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of 1 allele or antigen mismatch OR family donor with maximum 1 allele mismatch.
• Have adequate renal and hepatic functions as indicated by the following laboratory values:
• Serum creatinine ≤1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m² as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female)
• Serum bilirubin ≤1.5 mg/dL × upper limit of normal (ULN)
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 × ULN
• Alkaline phosphatase ≤2.5 × ULN

Exclusion Criteria:

• Documented chloroma
• Patients having AML M3
• Documented leukemic infiltration of CNS/cerebrospinal fluid
• Karnofsky performance score below < 60%
• Acute or chronic heart failure
• HIV infection, chronic viral hepatitis
• Severe neurological or psychiatric disorders
• Any circumstances that preclude the use of the drugs used within the protocol
• Prior allogeneic or autologous stem cell transplantation
• > 3 courses of prior chemotherapy
• Denied informed consent
• Pregnancy or denied of effective contraceptive method

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Clofarabine

Drug: Clofarabine; The present protocol aims to test the strategy of an early Reduced Intensity Conditioning (RIC) allo-SCT; in combination with a sequential preparative regimen for allo-SCT (Clofarabine, Intermediate dose Ara-C chemotherapy, followed by RIC with Cyclophosphamide, IV Busulfan and ATG; and delayed prophylactic infusion of donor lymphocytes (DLI) will be able to improve the outcome of patients with primary treatment failure AML.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of the survival rate at 2 years after transplantation	at 2 years after transplantation

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Mohamad Mohty, Phd, Chu Nantes

Publications and helpful links

General Publications

• Mohty M, Malard F, Blaise D, Milpied N, Socie G, Huynh A, Reman O, Yakoub-Agha I, Furst S, Guillaume T, Tabrizi R, Vigouroux S, Peterlin P, El-Cheikh J, Moreau P, Labopin M, Chevallier P. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia. Haematologica. 2017 Jan;102(1):184-191. doi: 10.3324/haematol.2016.150326. Epub 2016 Aug 25.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 24, 2010
• First Posted (ESTIMATE): August 25, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): December 5, 2014
• Last Update Submitted That Met QC Criteria: December 4, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: AML; primary induction failure
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Clofarabine
• Other Study ID Numbers: BRD 09/6-C