Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen

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 Chidamide intensified conditioning regimen in patients with Acute B cell Lymphoblast leukemia Underwenting Haploidenticl Peripheral blood Stem Cell Transplantation.

Detailed Description
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Haploidenticl Peripheral blood Stem Cell Transplantation should be offered to eligible patients with Acute B cell Lymphoblast leukemia whenever feasible. To further improve the outcome of transplantation patients with Acute B cell Lymphoblast leukemia, we developed a modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide. In this study, we tested the efficacy and feasibility of the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide in patients with Acute B cell Lymphoblast leukemia undergoing allogeneic peripheral blood stem cell transplantation.

Official Title
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Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen for Patients With Acute B Cell Lymphoblast Leukemia Underwenting Haploidenticl Peripheral Blood Stem Cell Transplantation

Conditions
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Peripheral Blood Stem Cell Transplantation

Intervention / Treatment
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* Drug: Ruxolitinib combined with Chidamide.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: high risk acute B cell lymphoblastic leukemia with the indications for allogeneic transplantation; 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; ALL patients with Ph positive;

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 Chidamide<br>Experimental: Ruxolitinib combined with Chidamide. All recipients in this arm received the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide. 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), chidamide (30 mg/day, twice per week from days -15 to -2), cytarabine (4g/m2/day, days -10 to -9), 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: Ruxolitinib combined with Chidamide.<br>* Drug: modified By/Cy conditioning regimen intensified by Ruxolitinib and Chidamide . Day -15 # Ruxolitinib 70mg bid, Chidamide 30 mg once; Day -14 # Ruxolitinib 70mg bid; Day -13 # Ruxolitinib 70mg bid; Day -12 # Ruxolitinib 70mg bid, Chidamide 30 mg once; Day -11 # Ruxolitinib 70mg bid; Day-10# Cytarabine 4g/m2/day CI , Ruxolitinib 60mg bid; Day- 9# Cytarabine 4g/m2/day CI, Ruxolitinib 60mg bid; Day- 8 # Busulfan 0.8mg/ kg Q6h iv, Ruxolitinib 50mg bid, Chidamide 30 mg once; Day- 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, Chidamide 30 mg once; 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, Chidamide 30 mg/day; Day-1# Ruxolitinib 5mg qd;<br>* Other names: Modified By/Cy conditioning regimen intensified by Ruxolitinib and Chidamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion 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 | 
| Proportion 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. | 365 days after transplantation | 
| Proportion 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 | 
| Failure-free survival (FFS) | Defined as the time from tranplantation to the earliest date that a participant died, had a relapse/progression of the underlying malignancy, required additional therapy for aGVHD, or demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD). | 365 days after transplantation | 
| infection rate | Defined as the proportion of participants who developed all kinds of infection. | 365 days after transplantation |