Clinical trial NCT01188174: Clofarabine/Ara-C Treatment Combined With Reduced-intensity Conditioning Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Primary Treatment Failure
Official title: Clofarabine/Ara-C Treatment Combined With Reduced-intensity Conditioning Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Primary Treatment Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: AML
Keywords: AML
primary induction failure
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2010-08-25
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of the survival rate at 2 years after transplantation
timeFrame: at 2 years after transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Caen
country: France
facility: CHU Caen
city: Lille
country: France
facility: CHRU lille
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Nantes
country: France
facility: Nantes University hospital
city: Paris
country: France
facility: Paris saint Louis
city: Strasbourg
country: France
facility: CHRU de Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: Nantes University Hospital
name: Mohamad Mohty, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.