Clinical trial NCT03793517: Decitabine Plus mBU/CY for High Risk Acute Leukemia With MRD Pre-HSCT
Official title: Decitabine Plus mBU/CY for High Risk Acute Leukemia With Minimal Residual Disease Pre-HSCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Stem Cell Transplant Complications
Leukemia, Myeloid, Acute
Leukemia Relapse
Keywords: high risk acute myeloid leukemia
hematopoietic stem cell transplantation
leukemia relapse
preparation regimen
decitabine
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2019-01-04
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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 high-risk molecular biomarkers who still have detectable minimal residual disease(MRD) pre-HSCT were at very high risk of relapse, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or refractory leukemia and myelodysplastiv syndrome. It was reported that the combination of decitabine, with busufan 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 patients with very high-risk AL and detectable MRD pre-HSCT.

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 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.

Eligibility criteria: Inclusion Criteria:

* acute leukemia patients with MLL-r,TLS-ERG,or SIL-TAL1,whose minimal residual disease were detectable pre-HSCT

Exclusion Criteria:

* pregnancy women
* uncontrolled severe infection

Primary outcomes:
measure: 1 year cumulative incidence of relapse
timeFrame: 1 year post allo-HSCT
measure: 2 year cumulative incidence of relapse
timeFrame: 2 years post allo-HSCT
Secondary outcomes:
measure: Non-relapse mortality
timeFrame: 1 year post allo-HSCT
measure: 1 year overall survival
timeFrame: 1 year post allo-HSCT
measure: 5 years overall survival
timeFrame: 5 years post allo-HSCT
measure: 1 year leukemia free survival
timeFrame: 1 year post allo-HSCT
measure: 5 years leukemia free survival
timeFrame: 5 years post allo-HSCT
measure: engraftment
timeFrame: 100 days post allo-HSCT
measure: Acute graft versus host disease
timeFrame: 100 days post allo-HSCT
measure: Chronic graft versus host disease
timeFrame: 1 years post allo-HSCT
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Institute of Hematology,Beijing
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Xiao-Jun Huang
role: STUDY_CHAIR
References: