Allogeneic Stem Cell Transplant With Clofarabine, Busulfan and Antithymocyte Globulin (ATG) for Adult Patients With High-risk Acute Myeloid Leukemia/Myelodysplastic Syndromes (AML/MDS) or Acute Lymphoblastic Leukemia (ALL)

NCT00863148 | Completed Phase 2 DMC

• 1 other identifier: BRD/08/07-J
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

Clofarabine is known to have a stronger anti-tumor effect than Fludarabine and has shown its efficacy in treating aggressive acute leukemias. In addition, evidence is that it is well-tolerated with manageable side effects especially in elderly patients. Thus, replacing Fludarabine with Clofarabine in a reduced intensity transplant regimen may provide a regimen with increased anti-tumor activity without adding significant risks of toxicity.The purpose of this study is to evaluate the efficacy and the safety of clofarabine in combination with IV busulfan and ATG as the backbone of a reduced intensity conditioning regimen for allogeneic stem cell transplantation for the treatment of patients with high-risk MDS/AML or ALL not eligible to conventional or standard myeloablative allo-SCT.

Conditions

MDS; AML; ALL; BAL

Keywords

MDS; AML; ALL; RIC; clofarabine; allo-HSCT; high-risk MDS/AML

Outcome Measures

Primary Outcomes (1)

• Relapse rate at one year after allo-SCT using the Clofarabine+Busulfan +Thymoglobuline reduced intensity conditioning regimen (CBT regimen).

  at one year

Interventions

Clofarabine in combination with IV busulfan and ATG DRUG

A conservative approach has been used for the determination of the dose due to the high risk studied population, e.g., decrease to 30 mg m²/day for a 4-day course of clofarabine. Clofarabine will be started at Day -8 to allow improvement of liver function tests, if any, by time of allo-HSCT. Clofarabine (C) 30 mg/m²/day for 4 days (day -8 to day-5). Busilvex (B): 3.2 mg/kg/day for 2 days (day -4 and day-3)Thymoglobuline (T): 2.5 mg/Kg/day for 2 days (day -2 and day-1). Graft (G) at day 0 GVHD prophylaxis: Cyclosporine 3 mg/kg/day starting day-1. Genzyme provided supplies of clofarabine for all patients included in the study.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65
• For patients younger than 50 years, cons-indication for the use of a standard myeloablative conditioning (history of hematopoietic stem cell transplantation autologous or allogeneic, or the presence of co-morbidities or medical history making prohibitive in terms toxicity using chemotherapy and / or high dose radiotherapy as judged by the referring physician) - MDS, ALL or AML at high risk, WHO THE biphenotypic-Score \<2
• Any primary diagnosis of high-risk MDS/AML or ALL eligible for a treatment by reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-SCT)
• Suitable donor available (related or matched unrelated)
• Cardiac: LV Ejection Fraction ≥ 50% by MUGA or Echocardiogram.
• Pulmonary: FEV1 and FVC ≥ 50% predicted, and DLCO (corrected for hemoglobin) ≥ 50% of predicted
• Adequate renal and hepatic function
• Performance status: Karnofsky ≥ 70%
• Informed consent signed by patient prior to enrolment

You may not qualify if:

• Age \<18
• Age \>65
• Known hypersensitivity to clofarabine or excipients- Other hematologic malignancies than ALL, AML and MDS
• Patients with prior standard allogeneic HSCT with grade \> 2 aGvHD
• Prior standard allogeneic transplantation if \< 2 months
• Contra-indication to one of the drug of the RIC regimen .
• Pregnant or lactating females
• Patient HIV+, Hep B+, Hep C+- Uncontrolled systemic infection
• Performance Status Score ECOG \> 2- Known central nervous system involvement with AML or ALL- Uncontrolled active infection of any kind or bleeding
• Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo the agents included in the conditioning regimen.
• For patients younger than 50 years, possibly indicating a standard myeloablative conditioning

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (6)

Hôpital Edouard Herriot

Lyon, 69437, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Nantes University hospital

Nantes, 44093, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

CHU Haut-Lévêque

Pessac, 33604, France

Location

CHRU Hautepierre

Strasbourg, 67098, France

Location

Related Publications (1)

• Chevallier P, Labopin M, Socie G, Tabrizi R, Furst S, Lioure B, Guillaume T, Delaunay J, de La Tour RP, Vigouroux S, El-Cheikh J, Blaise D, Michallet M, Bilger K, Milpied N, Moreau P, Mohty M. Results from a clofarabine-busulfan-containing, reduced-toxicity conditioning regimen prior to allogeneic stem cell transplantation: the phase 2 prospective CLORIC trial. Haematologica. 2014 Sep;99(9):1486-91. doi: 10.3324/haematol.2014.108563. Epub 2014 Jun 20.

  PMID: 24951467 DERIVED

MeSH Terms

Interventions

Clofarabine; Busulfan

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Design

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

Study Record Dates

• First Submitted: March 16, 2009
• First Posted: March 17, 2009
• Study Start: October 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 19, 2017

Record last verified: 2017-07

Locations

FR (6)