Refractory Leukemia, Relapse Leukemia, Stem Cell Transplant Complications
Conditions
Keywords
recurrent acute leukemia, refractory acute leukemia, preconditioning regimen, allogeneic stem cell transplantation
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.
Interventions
DRUGDecitabine
Decitabine 200mg.m-2.d-1 intravenously on days -12 and -11
DRUGmBU/CY and ATG
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 ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2
DRUGmBU/CY
hydroxycarbamide (80 mg·kg-1) orally on day -10 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·m-2) orally once on day -3
Sponsors
Peking University People's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model 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. 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 samples from patients would be 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 year after transplantation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* patients with relapsed acute leukemia * patients with acute leukemia in the third（or more）complete remission (CR3) status
Exclusion criteria
* pregnancy women * uncontrolled severe infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Non-relapse mortality | 1 year post allo-HSCT | The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT |
| Acute graft versus host disease | 100 days post allo-HSCT | The cumulative incidence of grade II-IV acute graft versus host disease |
| Chronic graft versus host disease | 1 years post allo-HSCT | The cumulative incidence of intermediate to severe chronic graft versus host disease |
| engraftment | 100 days post allo-HSCT | The total neutrophil and platelet engraftment rate |
| 1 year overall survival | 1 year post allo-HSCT | The overall survival at 1 year post allo-HSCT |
Countries
China
Contacts
Primary ContactXiao-Jun Huang
Backup ContactChen-Hua Yan
Outcome results
None listed