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)

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.

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Key information

Conditions

MDS ALL AML BAL

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hôpital Edouard Herriot, Lyon, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

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

Time frame: at one year

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Registry information

Official study 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.

Acronym: Cloric

Important dates

Study start: 2009
Primary completion: 2013
Study completion: 2013
First posted: Mar 17, 2009
Registry last updated: Jul 19, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed