Ruxolitinib and Decitabine for High Risk Hematological Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of Ruxolitinib and Decitabine intensified Conditioning Regimen in Patients with High Risk hematological malignancies undergoing allogeneic peripheral blood stem cell transplantation.

Detailed Description
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Allogeneic hematopoietic stem cell transplantation should be offered to eligible patients with high risk hematological malignancies whenever feasible. To further improve the outcome of transplantation patients with high risk hematological malignancies, the investigators developed a modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine. In this study, the investigators tested the efficacy and feasibility of the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine in Patients with high risk hematological malignancies undergoing allogeneic peripheral blood stem cell transplantation.

Official Title
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Ruxolitinib and Decitabine Intensified Conditioning Regimen for Patients With High Risk Hematological Malignancies Underwenting Allogeneic Stem Cell Transplantation

Conditions
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Peripheral Blood Stem Cell Transplantation

Intervention / Treatment
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* Drug: modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed/refractory acute leukemia with indications for allogeneic hematopoietic stem cell transplantation; High risk acute leukemia with indications for allogeneic hematopoietic stem cell transplantation; Medium to high risk myelodysplastic syndrome, myeloproliferative disease, myelodysplastic syndrome/myeloproliferative disease, Chronic myelomonocytic leukemia; Have matched sibling donors, ≥8/10 HLA matched unrelated donors or haploidentical donors All patients should aged 12 to 65 years; Liver function: ALT and AST≤2.5 times the upper limit of normal , bilirubin≤2 times the upper limit of normal; Renal function: creatinine ≤the upper limit of normal; Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness; Eastern Cooperative Oncology Group (ECOG) performance status ≤2; Have signed informed consent. Exclusion Criteria: pregnant women; Patients with mental illness or other states unable to comply with the protocol; AML patients with t (15;17);

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib combined with Decitabine<br>Ruxolitinib and Decitabine conditioning regimen All recipients in this arm received the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Decitabine. The conditioning regimen for allogeneic hematopoietic stem cell transplantation consist of ruxolitinib (35 mg bid [p.o.], days -15 to -10, diminishing to day -1), decitabine (20 mg/m2/day, days -15 to -10), cytarabine (4 g/m2/day, days -10 to -9 (for unrelated donors or haploidentical donors; and 4 g/m2/day, days -9 for sibling donors)), busulfan (0.8mg/kg, Q6h, days -8 to -6), cyclophosphamide (1.8 g/m2/day, days -5 to -4);carmustine(BCNU)(250mg/m2/day, day -3), | Drug: modified By/Cy conditioning regimen intensified by Ruxolitinib and Decitabine<br>* Day -15 to -14 ： Decitabine 20 mg/m2/day, Ruxolitinib 70mg bid; Day-10： Cytarabine 1.6 g/m2/day CI (only for Haploidentical and unrelated donor), Ruxolitinib 60mg bid; Day- 9： Cytarabine 4g/m2/day CI, Ruxolitinib 60mg bid; Day- 8 to -7： Busulfan 0.8mg/kg Q6h iv, Ruxolitinib 50mg bid; Day-6: Busulfan 0.8mg/kg Q6h iv, Ruxolitinib 40mg bid; Day-5： Cyclophosphamide 1.8 g/m2/day CI, Ruxolitinib 30mg bid; Day-4： Cyclophosphamide 1.8 g/m2/day CI, Ruxolitinib 20mg bid; Day-3： Carmustine 250mg/m2/day iv, Ruxolitinib 10mg bid; Day-2： Ruxolitinib 5mg bid; Day-1： Ruxolitinib 5mg qd;<br>* Other names: Ruxolitinib and Decitabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants relapse as assessed by NCCN (National Comprehensive Cancer Network )criteria | Defined as the proportion of participants whose underlying malignancy relapsed. | 365 days after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS(disease-free survival ) | DFS was defined as survival with no evidence of relapse or progression. | 365 days after transplantation | 
| TRM(treatment-related mortality ) | Defined as the proportion of subjects who died due to causes other than malignancy relapse. | 365 days after transplantation | 
| Number of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria) | Defined as the proportion of participants who developed acute GVHD. | 100 days after transplantation | 
| Number of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria) | Defined as the proportion of participants who developed chronic GVHD. | 365 days after transplantation | 
| OS(overall survival ) | OS was defined as the time from transplantation to death due to any cause. | 365 days after transplantation | 
| GRFS (GVHD free, relapse free survival) | GVHD-free, relapse-free survival (GRFS) was defined as survival with no evidence of grade III-IV acute GVHD or cGVHD requiring immunosuppressive treatment, and without disease recurrence or death from any cause during the first year after transplantation. | 365 days after transplantation | 
| infection rate | Defined as the proportion of participants who developed all kinds of infection. | 365 days after transplantation |