Cloric: 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)

Sponsor

Nantes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00863148

Collaborator

(none)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
MDS AML ALL BAL	Drug: Clofarabine in combination with IV busulfan and ATG	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hôpital Edouard Herriot	Lyon	France	69437
2	Institut Paoli Calmettes	Marseille	France	13273
3	Nantes University hospital	Nantes	France	44093
4	Hôpital Saint Louis	Paris	France	75475
5	CHU Haut-Lévêque	Pessac	France	33604
6	CHRU Hautepierre	Strasbourg	France	67098