M-PTCy vs BuCy in Haploidentical HSCT for Acute Leukemia

Study Overview
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Brief Summary
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This study intends to evaluate the efficiency and safety of M-PTCy as conditioning regimen in Haploidentical HSCT for Acute Leukemia, so as to provide a new conditioning regimen for allogeneic hematopoietic cell transplantation.

Detailed Description
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Haploidentical related donor transplantation is now considered an important alternative to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Posttransplant cyclophosphamide (PTCy) has revolutionized Haplo HCT with acceptable rates of engraftment, graft-versus-host disease (GVHD), relapse, and survival.To prolonger PFS, OS and alleviate GVHD, we combined Mitoxantrone liposomes with PTCy as conditioning regimen in allogeneic hematopoietic cell transplantation.

Official Title
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An Multicenter, Randomized, Controlled, Prospective Clinical Study of Mitoxantrone Liposome Combined With PTCy as Conditioning Regimen in Allo-HSCT in Acute Leukemia

Conditions
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Acute Leukemia

Intervention / Treatment
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* Drug: mitoxantrone liposome
* Drug: ATG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients meet the diagnostic criteria for acute leukemia(except APL). Expecting life span is more than 3 months. The patients intended allogeneic hematopoietic stem cell transplantation. Exclusion Criteria: Previously received doxorubicin or other anthracycline therapy, the total cumulative dose of doxorubicin≥360 mg/m2. Cardiac function and disease meet one of the following conditions: Long QTc syndrome or QTc intervalgt≥480 ms; Complete left bundle branch block, grade II or III Degree atrioventricular block; Severe, uncontrolled arrhythmia requiring drug treatment; New York Society of Cardiology class ≥ II; Cardiac ejection fraction (LVEF) lower than 50% or lower than the study The lower limit of the central laboratory test value range; History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, clinically serious pericardial disease history within 6 months before recruitment, or ECG evidence of acute ischemia or active conduction system abnormalities. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN); Total bilirubin > 1.5 times upper limit of normal; Serum creatinine > 1.5 times the upper limit of normal. Suffering from other malignant tumors in the past or at the same time ; Exclude patients with severe active infection or other underlying diseases who cannot tolerate chemotherapy; Human immunodeficiency virus (HIV) infected patients (HIV antibody positive); Active hepatitis B and C infection； Pregnant women, lactating women, and patients who refuse to take effective contraceptive measures during the study; Severe mental disorders who do not cooperate with treatment; Judgment by the investigator , There are patients who are not suitable to participate in this study.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M+PTCy group<br>For the M-PTCy group, Mitoxantrone liposomes with 36mg/m2 and Bu 3.2mg/kg -5 to -4, Flu 30mg/m2 -12 to -9, Ara-C 1.5g/m2 -12 to -9，CTX 15mg/kg/d -3 to -2, was used as conditioning regimen, Post Transplant Cyclophosphamide 50 mg/kg IV daily on days +3 and +4. | Drug: mitoxantrone liposome<br>* Mitoxantrone liposomes with 36mg/m2 and Bu 3.2mg/kg -5 to -4, Flu 30mg/m2 -12 to -9, Ara-C 1.5g/m2 -12 to -9，CTX 15mg/kg/d -3 to -2, was used as conditioning regimen, Post Transplant Cyclophosphamide 50 mg/kg IV daily on days +3 and +4.<br>* Other names: Fludarabine,Cytarabine,busulfan,Cyclophosphamide,MMF,Tacrolimus Capsules;|
| Active Comparator: BuCy group<br>For the BUCY group, the conditioning regimen involved Ara-C 2g/m2 q12h -8, BU 3.2 mg/kg -7 to -5,CTX 1.8 g/m2 -4 to -3, to prevent GVHD, MTX 15mg/m2 +1d, 10mg/m2 +3,+6,+11,CsA 3mg/kg/d from -8d,MMF 1g q12h from -8d， ATG 2.5mg/kg/d -5 to -2. | Drug: ATG<br>* Control group:the conditioning regimen involved Ara-C 2g/m2 q12h -8, BU 3.2 mg/kg -7 to -5,CTX 1.8 g/m2 -4 to -3, to prevent GVHD, MTX 15mg/m2 +1d, 10mg/m2 +3,+6,+11,CsA 3mg/kg/d from -8d,MMF 1g q12h from -8d， ATG 2.5mg/kg/d -5 to -2.<br>* Other names: MECCNU,Hu,Cytarabine,busulfan,Cyclophosphamide,MTX,CsA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | It is defined as the total survival of a patient after CR until the tumor recurrence or death from any cause. | From the 1st day to 2 years after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The time from randomization to death from any cause. | From the 1st day to 2 years after enrollment | 
| incidence of GVHD | The incidence of graft-versus-host disease | From the 1st day to 2 years after enrollment | 
| CMV and EBV activation | The incidencance of cytomegalovirus and Epstein-barr virus infection | From the 1st day to 2 years after enrollment |