M-PTCy vs BuCy in Haploidentical HSCT for Acute Leukemia

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05739630

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Leukemia	Drug: mitoxantrone liposome Drug: ATG	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 31, 2024

Anticipated Study Completion Date :

Jan 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: M+PTCy group 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 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. Other Names: Fludarabine,Cytarabine,busulfan,Cyclophosphamide,MMF,Tacrolimus Capsules
Active Comparator: BuCy group 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 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. Other Names: MECCNU,Hu,Cytarabine,busulfan,Cyclophosphamide,MTX,CsA

Arm

Intervention/Treatment

Experimental: M+PTCy group

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

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.

Other Names:

Fludarabine,Cytarabine,busulfan,Cyclophosphamide,MMF,Tacrolimus Capsules

Active Comparator: BuCy group

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

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.

Other Names:

MECCNU,Hu,Cytarabine,busulfan,Cyclophosphamide,MTX,CsA

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.