Study of Busulfan and FLAG Conditioning Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor) Conditioning Regimen in Patients with Relapsed/refractory Acute Leukemia undergoing allogeneic peripheral blood stem cell transplantation.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only way to cure relapsed/refractory acute leukemia. Busulfan/Cyclophosphamide (BuCy, Cytarabine, Busulfan, Cyclophosphamide) has been a classical conditioning regimen for allo-SCT. Substitution of Cyclophosphamide in the BuCy regimen with Fludarabine (BuF) resulted in reduced toxicity and similar efficacy. FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor) is a chemotherapy regimen that has been proved to be effective for relapsed/refractory acute leukemia as salvage therapy. To reduce the relapse and improve the survival of those patients with relapsed/refractory acute leukemia who receive allo-SCT, the novel conditioning regimen consisting of Busulfan/FLAG was developed. The combination of Bu and FLAG without interval shortens the duration of conditioning and the pneutropenic period of the patient compared with successive administration of FLAG followed with BuF. In addition, regarding the established safety and efficacy of BuF and FLAG, it is reasonable to expect similar safety and enhanced antileukemic efficacy for Bu/FLAG compared with BuF. In this study, the safety and efficacy of this regimen in patients with relapsed/refractory acute leukemia undergoing allogeneic peripheral blood stem cell transplantation was investigated.

Official Title
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Safety and Efficacy Study of Busulfan/FLAG Conditioning Regimen in Patients With Relapsed/Refractory Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation

Conditions
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Leukemia

Intervention / Treatment
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* Drug: Busulfan (Zhejiang Otsuka Pharmaceutical Co. Ltd)
* Drug: Cytarabine(Actavis Italy S.p.A)
* Drug: Fludarabine (Bayer)
* Drug: granulocyte colony-stimulating factor (KirinKunpeng)
* Drug: rabbit ATG（Sanofi/Genzyme）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: relapsed/refractory acute leukemia regardless of cytogenetics All patients should aged 12 to 65 years Have matched sibling donors, ≥8/10 HLA(human leukocyte antigen) matched unrelated donors or haploidentical donors Patients without any uncontrolled infections or without severe pulmonary, renal, hepatic or cardiac diseases Exclusion Criteria: Patients aged less than 12 years old Patients with any uncontrolled infections or with severe pulmonary, renal, hepatic or cardiac diseases Acute myeloid leukemia patients with t (15;17)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Busulfan/FLAG conditioning regimen<br>All recipients in this arm received the conditioning regimen consisting of Busulfan/FLAG (fludarabine, cytarabine and granulocyte colony-stimulating factor). The conditioning regimen for peripheral blood stem cell transplantation consisted of busulfan (3.2 mg/kg/ day intravenously [i.v.], days -10 to -8), fludarabine (30 mg/m2, day -7 to -3), cytarabine (1.6 g/m2/day, days -7 to -3), granulocyte colony-stimulating factor (5 ug/ kg, day -8 to -3). ATG (Thymoglobuline, rabbit) for haploidentical and matched unrelated donors transplantation recipients was used on 2.5 mg/kg/d from days -5 to -2). | Drug: Busulfan (Zhejiang Otsuka Pharmaceutical Co. Ltd)<br>* busulfan (3.2 mg/kg/day intravenously [i.v.], days -10 to -8)<br>* Other names: Myleran, Busulfex;Drug: Cytarabine(Actavis Italy S.p.A)<br>* cytarabine (1.6 g/m2/day, days -7 to -3)<br>* Other names: Ara-C;Drug: Fludarabine (Bayer)<br>* fludarabine (30 mg/m2, day -7 to -3),<br>* Other names: fludarabine phosphate (Fludara);Drug: granulocyte colony-stimulating factor (KirinKunpeng)<br>* granulocyte colony-stimulating factor (5 ug/kg, day -8 to granulocyte recovery)<br>* Other names: G-CSF（granulocyte colony-stimulating factor ）;Drug: rabbit ATG（Sanofi/Genzyme）<br>* ATG; thymoglobuline, rabbit;2.5 mg/kg/day, days -5 to -2<br>* Other names: Thymoglobuline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria |  | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Complete Remission as assessed by NCCN (National Comprehensive Cancer Network )criteria |  | 30 days | 
| DFS(disease-free survival ) |  | two years | 
| TRM(treatment-related mortality ) |  | two years | 
| Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria) |  | three months | 
| Number of participants with Regimen-related adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allogeneic peripheral blood stem cell transplantation, conditioning regimen, acute leukemia, relapsed/refractory