Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia
- Conditions
- Stem Cell Transplant ComplicationsRelapse LeukemiaRefractory Leukemia
- Interventions
- Registration Number
- NCT03799224
- Lead Sponsor
- Peking University People's Hospital
- Brief Summary
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly causes of transplant failure. We reported previously that patients with relapse or refractory AL were at very high risk of relapse post allo-HSCT, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or refractory leukemia and myelodysplastic syndrome. It was reported that the combination of decitabine, with busulfan and cyclophosphamide as a preparative regimen for allo-HSCT using HLA-matching donors was safe and effective. In this prospective, single-arm clinical trial, we aimed to examine the efficacy of combining decitabine with modified busulfan and cyclophosphamide (mBU/CY) as a preparative regimen for allo-HSCT in recurrent and refractory AL patients.
- Detailed Description
Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG (thymoglobulin; Sang Stat, France) consisting of cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg·m-2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.
BM(bone marrow) samples from patients were obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 years after transplantation.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 55
- patients with relapsed acute leukemia
- patients with acute leukemia in the third（or more）complete remission (CR3) status
- pregnancy women
- uncontrolled severe infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Decitabine plus mBU/CY for HLA-mismatched HSCT mBU/CY and ATG Decitabine plus mBU/CY as precondition regimen for recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT Details: The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2 Decitabine plus mBU/CY for matched sibling transplant mBU/CY Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD (minimal residual disease) at the time of matched sibling transplant. Details: In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3. Decitabine plus mBU/CY for HLA-mismatched HSCT Decitabine Decitabine plus mBU/CY as precondition regimen for recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT Details: The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2 Decitabine plus mBU/CY for matched sibling transplant Decitabine Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD (minimal residual disease) at the time of matched sibling transplant. Details: In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3.
- Primary Outcome Measures
Name Time Method 1 year cumulative incidence of relapse 1 year post allo-HSCT The cumulative incidence of relapse at 1 year post allo-HSCT
2 year cumulative incidence of relapse 2 years post allo-HSCT The cumulative incidence of relapse at 2 years post allo-HSCT
- Secondary Outcome Measures
Name Time Method Chronic graft versus host disease 1 years post allo-HSCT The cumulative incidence of intermediate to severe chronic graft versus host disease
Non-relapse mortality 1 year post allo-HSCT The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT
engraftment 100 days post allo-HSCT The total neutrophil and platelet engraftment rate
Acute graft versus host disease 100 days post allo-HSCT The cumulative incidence of grade II-IV acute graft versus host disease
1 year overall survival 1 year post allo-HSCT The overall survival at 1 year post allo-HSCT
5 years overall survival 5 years post allo-HSCT] 1 year leukemia free survival The overall survival at 5 years post allo-HSCT
1 year leukemia free survival 1 year post allo-HSCT The leukemia free survival at 1 years post allo-HSCT
5 years leukemia free survival 5 years post allo-HSCT The leukemia free survival at 5 years post allo-HSCT
Trial Locations
- Locations (1)
Peking University Institute of Hematology,Beijing
🇨🇳Beijing, Beijing, China