Fractionated Busulfan Conditioning Regimen for Allo-HSCT in Non-remission Myeloid Malignancies

Study Overview
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Brief Summary
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The goal of this single-arm phase II study is to test in patients with non-remission myeloid malignancies undergoing allogeneic hemopoietic stem-cell transplantation (allo-HSCT). The main question it aims to answer are: The safety and efficacy of fractionated busulfan Combined With Chidamide/Fludarabine/Cytarabine(ChiFAB) conditioning regimen in increasing the overall survival rate in patients with non-remission myeloid malignancies after allo-HSCT. The efficacy of fractionated busulfan conditioning regimen in reducing the recurrence rate in patients with non-remission myeloid malignancies after allo-HSCT. Participants will receive fractionated busulfan-based ChiFAB conditioning regimen (busulfan 3.2mg/kg d-13, -12, 1.6mg/kg d-6 -3, fludarabine 35mg/m2 d-6 -2, cytarabine 1g/m2,d-6 -2, chidamide 30mg d-13,-10,-6,-3) before allo-HSCT.

Official Title
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Fractionated Busulfan Combined With Chidamide/Fludarabine/Cytarabine (ChiFAB) With Allogeneic Hematopoietic Stem-Cell Transplantation in Non-remission Myeloid Malignancies: a Phase II Study

Conditions
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Myeloid Malignancies

Intervention / Treatment
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* Drug: fractionated busulfan-based conditioning regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old and ≤ 65 years old when signing the Informed Consent Form (ICF); KPS score > 60 or ECOG score 0-2; The expected survival period > 3 months; Those who did not achieve complete remission after 2 or more chemotherapy regimens. The proportion of blasts on bone marrow smears before transplantation was ≥5%. Those who have no central nervous system involvement or serious functional damage to important organs of the body; Fully understand and be informed of this study and sign the ICF; willing to follow and have the ability to complete all test procedures; Exclusion Criteria: Serious basic diseases of important organs: such as myocardial infarction, chronic cardiac insufficiency, decompensated hepatic insufficiency, renal function, gastrointestinal insufficiency, etc.; Uncontrolled active infection (including bacterial, fungal, or viral infection), and drug treatment is ineffective; Participating in other clinical studies, or planning to start treatment in this study and less than 4 weeks before the end of treatment in the previous clinical study; Combined with other malignant tumors and require treatment; Pregnant or lactating females; Patients with known history of human immunodeficiency virus (HIV) virus infection and/or acquired immunodeficiency syndrome; Patients with active chronic hepatitis B or active hepatitis C; History of prolonged QT syndrome; Patients considered by other researchers to be unsuitable for this study

Ages Eligible for Study
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Minimum Age: 18 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: fractionated busulfan<br>fractionated busulfan-based ChiFAB conditioning regimen: busulfan 3.2mg/kg d-13, -12, 1.6mg/kg d-6 -3, fludarabine 35mg/m2 d-6 -2 cytarabine 1g/m2,d-6 -2 chidamide 30mg d-13,-10,-6,-3 | Drug: fractionated busulfan-based conditioning regimen<br>* Drug: Chidamide 30 mg oral twice weekly for 2 weeks Drug: Fludarabine 35 mg/m2 intravenously daily for 5 days in the 2nd week Drug: Cytarabine 1 g/m2 intravenously for 5 days in the 2nd week Drug: Busulfan 3.2 mg/kg intravenously daily for 2 days in the 1st week, 1.6 mg/kg intravenously daily for 4 days in the 2nd week Procedure/Surgery: allogeneic hematopoietic stem cell transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall survival of this group of patients at the end of 2 year | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-relapse mortality (NRM) | Non-relapse mortality of this group of patients at the end of 6 months | 6 months | 
| Relapse rate | Relapse rate of this group of patients at the end of 2 year | 2 years | 
| Cumulative incidence of acute graft versus host disease (aGVHD) | Cumulative incidence of acute graft versus host disease (aGVHD) of this group of patients at day+100 | Day +100 | 
| Cumulative incidence of chronic graft versus host disease (cGVHD) | Cumulative incidence of chronic graft versus host disease (cGVHD) of this group of patients at the end of 2 year | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myeloid malignancies, allo-HSCT