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

AML Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01188174
• Other study ID #: BRD 09/6-C
• Status: Completed
• Phase: Phase 2
• First received: August 11, 2010
• Last updated: December 4, 2014
• Start date: July 2010
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• AML
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	CHU Caen	Caen
France	CHRU lille	Lille
France	Hôpital Edouard Herriot	Lyon
France	Institut Paoli Calmette	Marseille
France	Nantes University hospital	Nantes
France	Paris saint Louis	Paris
France	CHRU de Strasbourg	Strasbourg
France	CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the survival rate at 2 years after transplantation		at 2 years after transplantation	Yes