Study of Busulfan and FLAG Conditioning Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation
- Conditions
- Leukemia
- Interventions
- Drug: Cytarabine(Actavis Italy S.p.A)Drug: granulocyte colony-stimulating factor (KirinKunpeng)
- Registration Number
- NCT02784561
- Lead Sponsor
- Chinese PLA General Hospital
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 80
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Busulfan/FLAG conditioning regimen Busulfan (Zhejiang Otsuka Pharmaceutical Co. Ltd) 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). Busulfan/FLAG conditioning regimen Cytarabine(Actavis Italy S.p.A) 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). Busulfan/FLAG conditioning regimen Fludarabine (Bayer) 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). Busulfan/FLAG conditioning regimen granulocyte colony-stimulating factor (KirinKunpeng) 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). Busulfan/FLAG conditioning regimen rabbit ATG（Sanofi/Genzyme） 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).
- Primary Outcome Measures
Name Time Method Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria two years
- Secondary Outcome Measures
Name Time Method 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