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

NCT ID: NCT01188174

Last Updated: 2014-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Study Completion Date

2014-12-31

Brief Summary

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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

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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

Conditions

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AML

Keywords

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AML primary induction failure

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Clofarabine

Group Type EXPERIMENTAL

Clofarabine

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nantes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mohamad Mohty, Phd

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

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CHU de Bordeaux

Bordeaux, , France

Site Status

CHU Caen

Caen, , France

Site Status

CHRU lille

Lille, , France

Site Status

Hôpital Edouard Herriot

Lyon, , France

Site Status

Institut Paoli Calmette

Marseille, , France

Site Status

Nantes University hospital

Nantes, , France

Site Status

Paris saint Louis

Paris, , France

Site Status

CHRU de Strasbourg

Strasbourg, , France

Site Status

CHU Toulouse

Toulouse, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 27561720 (View on PubMed)

Other Identifiers

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BRD 09/6-C

Identifier Type: -

Identifier Source: org_study_id