M-PTCy vs BuCy in Haploidentical HSCT for Acute Leukemia

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia
• Intervention / Treatment: Drug: mitoxantrone liposome; Drug: ATG

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Huizhu Kang, MD; Phone Number: 8761925608; Email: khz11826@sina.com
• Study Contact Backup: Name: Ruju Wang, MD; Phone Number: 13912629420; Email: wrja0515@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Yue Han; Phone Number: +86 13901551669; Email: hanyuesz@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The patients meet the diagnostic criteria for acute leukemia(except APL).
2. Expecting life span is more than 3 months.
3. The patients intended allogeneic hematopoietic stem cell transplantation.

Exclusion Criteria:

1. Previously received doxorubicin or other anthracycline therapy, the total cumulative dose of doxorubicin≥360 mg/m2.

2. Cardiac function and disease meet one of the following conditions:

   1. Long QTc syndrome or QTc intervalgt≥480 ms;
   2. Complete left bundle branch block, grade II or III Degree atrioventricular block;
   3. Severe, uncontrolled arrhythmia requiring drug treatment;
   4. New York Society of Cardiology class ≥ II;
   5. Cardiac ejection fraction (LVEF) lower than 50% or lower than the study The lower limit of the central laboratory test value range;
   6. 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.
3. 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.
4. Suffering from other malignant tumors in the past or at the same time ;
5. Exclude patients with severe active infection or other underlying diseases who cannot tolerate chemotherapy;
6. Human immunodeficiency virus (HIV) infected patients (HIV antibody positive);
7. Active hepatitis B and C infection；
8. Pregnant women, lactating women, and patients who refuse to take effective contraceptive measures during the study;
9. Severe mental disorders who do not cooperate with treatment;
10. Judgment by the investigator , There are patients who are not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Yue Han, MD/phD, study principle investigator

Publications and helpful links

General Publications

• Apperley J, Niederwieser D, Huang XJ, Nagler A, Fuchs E, Szer J, Kodera Y. Reprint of: Haploidentical Hematopoietic Stem Cell Transplantation: A Global Overview Comparing Asia, the European Union, and the United States. Biol Blood Marrow Transplant. 2016 Mar;22(3 Suppl):S15-8. doi: 10.1016/j.bbmt.2016.01.006.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): January 31, 2025

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Estimate): February 22, 2023

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Acute Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Calcineurin Inhibitors; Cyclophosphamide; Fludarabine; Cytarabine; Mitoxantrone; Tacrolimus; Busulfan
• Other Study ID Numbers: 2023003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No