Clinical trial NCT00863148: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: MDS
AML
ALL
BAL
Keywords: MDS
AML
ALL
RIC
clofarabine
allo-HSCT
high-risk MDS/AML
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2009-03-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Relapse rate at one year after allo-SCT using the Clofarabine+Busulfan +Thymoglobuline reduced intensity conditioning regimen (CBT regimen).
timeFrame: at one year
Secondary outcomes:
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Nantes University hospital
city: Paris
country: France
facility: Hôpital Saint Louis
city: Pessac
country: France
facility: CHU Haut-Lévêque
city: Strasbourg
country: France
facility: CHRU Hautepierre
Study officials:
References:
citation: 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.