This study aims to determine whether the recurrence rate of high-risk acute myeloid leukemia CR1 patients who received allogeneic hematopoietic stem cell transplantation with the Ruxolitinib, Decitabine combined with Bu/Cy or BuF intensive pretreatment regimen is reduced compared with the traditional Bu/Cy or BuFpretreatment regimen.
Allogeneic hematopoietic stem cell transplantation is the only radical treatment for high-risk acute myeloid leukemia (AML), but the traditional Bu/Cy pretreatment regimen is highly toxic and has a high recurrence rate after transplantation (the long-term survival rate is only 10-30%). Although the existing improved regimens such as sequential chemotherapy can reduce the leukemia burden, they lead to prolonged myelosuppression time (17-39 days) and a non-relapse mortality rate as high as 17.2%. There is an urgent need to develop new pretreatment regimens that have both strong anti-leukemia effects and low toxicity. Studies have found that the JAK-STAT signaling pathway is generally abnormally activated in hematological tumors such as AML. The objective response rate of Ruxolitinib (a JAK1/2 inhibitor) as a monotherapy for relapsed/refractory leukemia reached 45%. When combined with the demethylated drug decitabine, it can synergistically inhibit leukemia cells. Clinical data show that decitabine reduces the recurrence rate after transplantation by 20% (15.0% vs 38.3%), and the combination of the two has good safety. The main adverse reaction is grade 1-2 hematological toxicity. Our center innovatively proposed the Rux-Dec-mBu/Cy or BuF combined regimen: integrating Ruxolitinib (step-based dose reduction) and decitabine (20mg/m²/d) on the basis of the classic Bu/Cy or BuF. Previous single-arm studies have shown that the one-year recurrence rate of CR1 patients is 0%, and the incidence of toxicity above grade 3 is less than 11%. This study intends to conduct a multicenter randomized controlled trial to verify the superiority of this regimen in reducing recurrence after transplantation in patients with high-risk AML CR1. Its core advantage lies in simultaneously achieving anti-leukemia enhancement (through JAK-STAT targeting and epigenetic regulation) and controllable toxicity (The median grain deficiency time was shortened to 14 days).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
1. Decitabine: 20 mg/m²/day, administered from Day -15 to Day -10. 2. Ruxolitinib: * 10 mg twice daily (bid), Day -15 to Day -5 * 5 mg twice daily (bid), Day -4 to Day -3 * 5 mg once daily (Qd), Day -2
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGGRFS
GVHD-free, relapse-free survival (GRFS) was defined as a composite endpoint of death from any cause, disease relapse, grade Ⅲ-Ⅳ acute GVHD, or chronic GVHD requiring systemic immunosuppression therapy.
Time frame: 1 year
Cumulative recurrence rate (CIR)
Calculated from the first day after stem cell infusion to the last follow-up, the number of patients with hematological or MRD recurrence/the total number of cases ×100%. The definition of hematological recurrence: After remission, patients present with one of the following three conditions: (1) ≥5% of primary lymphocytes and immature lymphocytes in the bone marrow; (2) Extramedullary leukemia occurs; (3) Leukemia cells were found in peripheral blood smears. The definition of MRD recurrence: Leukemia cells are detected by flow cytometry or molecular biology.
Time frame: 1 years after transplantation
Progression-Free Survival（PFS）
The time from the date of transplantation to the recurrence of leukemia or death for any reason.
Time frame: 1 years after transplantation
CR rate
The proportion of bone marrow in complete remission from the first day after stem cell infusion to +30 days.
Time frame: 30 days after transplantation
The incidence of aGVHD
Calculated from the first day after stem cell infusion, the time from the occurrence of aGVHD, the time of recurrence or death. The actual incidence rate is the number of patients who occur/the total number of cases ×100%.
Time frame: 100 days after transplantation
The incidence of cGVHD
Calculated from the first day after stem cell infusion, the time from the occurrence of cGVHD, the time of recurrence or death. The actual incidence rate is the number of patients who occur/the total number of cases ×100%.
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Time frame: 1 years after transplantation
Disease-free survival rate (DFS)
Disease-free survival rate (DFS) refers to the survival period without evidence of recurrence or progression.
Time frame: 1 years after transplantation
Treatment-related safety indicators
Mainly include bacterial infection, viral infection, fungal infection, and PTLD from the time calculated after transplantation to the last follow-up.
Time frame: 1 years after transplantation
Non-relapse mortality
Non-relapse mortality (NRM) was defined as death from any cause other than disease relapse.
Time frame: 1 year
The cumulative incidence of virus reactivation
The cumulative incidence of virus reactivation by Day +180 days post-transplantation was defined as the proportion of virus reactivation occurring at any monitoring point during days 180 post-transplant.
Time frame: Day +180 days post-transplantation
Graft failure
Graft failure was defined as non-engraftment (ie, autologous reconstitution) or graft rejection (ie, secondary loss of donor chimerism) at +28 days
Time frame: +28 days after transplantation
Neutrophil engraftment
Neutrophil engraftment was defined as the first of three consecutive days with a neutrophil count \>0.5 ×109/L.
Time frame: +28 days after transplantation
Platelet engraftment
Platelet engraftment was defined as the first of seven consecutive days with a platelet count \>20×109/L without transfusion support.
Time frame: +28 days after transplantation
CD4+T cell reconstitution
CD4+T cell reconstitution was defined as CD4+ T cell count ≥ 50/μL in two consecutive measurements within the first 100 days post-transplantation.
Time frame: the first 100 days post-transplantation