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)

AML Clinical Trial

— Cloric  

Official title:

A Phase II Open-label, Multicenter, Non Randomized Study Evaluating the Efficacy and the Safety of Clofarabine in Combination With IV Busulfan and Thymoglobulin (CBT) as a Reduced Intensity Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation in Adult Patients With High-risk AML, MDS or ALL.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00863148
• Other study ID #: BRD/08/07-J
• Status: Completed
• Phase: Phase 2
• First received: March 16, 2009
• Last updated: July 18, 2017
• Start date: October 2009
• Est. completion date: June 2013

Study information

• Verified date: July 2017
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 .

• Patient with > 3 treatment lines prior to inclusion

• 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

Related Conditions & MeSH terms

• ALL
• AML
• BAL
• MDS

Intervention

Drug:
• Clofarabine in combination with IV busulfan and ATG
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.

Locations

Country	Name	City	State
France	Hôpital Edouard Herriot	Lyon
France	Institut Paoli Calmettes	Marseille
France	Nantes University hospital	Nantes
France	Hôpital Saint Louis	Paris
France	CHU Haut-Lévêque	Pessac
France	CHRU Hautepierre	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse rate at one year after allo-SCT using the Clofarabine+Busulfan +Thymoglobuline reduced intensity conditioning regimen (CBT regimen).		at one year