Hematopoietic Stem Cell Transplantation for Patients With Thalassemia Major: A Multicenter, Prospective Clinical Study

The only curative therapy for thalassemia major remains the replacement of the defective erythropoiesis by allogeneic hematopoietic stem cell transplantation(allo-HSCT). We conduct a prospective multicenter study to evaluate the efficacy of allo-HSCT in the treatment of thalassemia major.

Study Overview

• Status: Completed
• Conditions: Thalassemia Major
• Intervention / Treatment: Drug: Methotrexate; Drug: Tacrolimus; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Thymoglobulin; Drug: cyclosporine A; Drug: Mycophenolate mofetil

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the established curative option for thalassemia major (TM). Previous study has predicted that more than 90% of TM patients can survive after allo-HSCT with a thalassemia-free survival (TFS) in around 80% of them.The purpose of this study is to evaluate the efficacy of allo-HSCT in the treatment of thalassemia major.

• Study Type: Interventional
• Enrollment (Actual): 823
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China, 510515
      • First Affiliated Hospital of Guangxi Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with thalassemia major.
2. Indication of hematopoietic stem cell transplantation.
3. A cardiac ejection fraction of >50%; normal pulmonary function tests and pulmonary examination results; and normal kidney function.

Exclusion Criteria:

1. Aspartate aminotransferase levels > 4-fold the upper limit of the normal range for our institution's lab criteria;
2. Uncontrolled bacterial, viral or fungal infections;
3. Any other restriction for transplantation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSD-HSCT; matched sibling donors hematopoietic stem cell transplantation	Drug: Methotrexate; Methotrexate; Other Names: MTX; Drug: Busulfan; Busulfan（4 mg/kg/day,4 days）; Other Names: Bu; Drug: Cyclophosphamide; Cyclophosphamide（50 mg/kg/day,4 days）; Other Names: Cy; Drug: Fludarabine; Fludarabine（50 mg/m2/day,3 days）; Other Names: Flu; Drug: Thymoglobulin; Thymoglobulin（2.5 mg/kg/day,4 days）; Other Names: ATG; Drug: cyclosporine A; cyclosporine A; Other Names: CsA; Drug: Mycophenolate mofetil; Mycophenolate mofetil（0.25g/day）; Other Names: MMF
Experimental: URD-HSCT; unrelated donor hematopoietic stem cell transplantation	Drug: Methotrexate; Methotrexate; Other Names: MTX; Drug: Tacrolimus; Tacrolimus; Other Names: FK506; Drug: Busulfan; Busulfan（4 mg/kg/day,4 days）; Other Names: Bu; Drug: Cyclophosphamide; Cyclophosphamide（50 mg/kg/day,4 days）; Other Names: Cy; Drug: Fludarabine; Fludarabine（50 mg/m2/day,3 days）; Other Names: Flu; Drug: Thymoglobulin; Thymoglobulin（2.5 mg/kg/day,4 days）; Other Names: ATG; Drug: Mycophenolate mofetil; Mycophenolate mofetil（0.25g/day）; Other Names: MMF
Experimental: haplo-HSCT; haplo-identical hematopoietic stem cell transplantation	Drug: Methotrexate; Methotrexate; Other Names: MTX; Drug: Tacrolimus; Tacrolimus; Other Names: FK506; Drug: Busulfan; Busulfan（4 mg/kg/day,4 days）; Other Names: Bu; Drug: Cyclophosphamide; Cyclophosphamide（50 mg/kg/day,4 days）; Other Names: Cy; Drug: Fludarabine; Fludarabine（50 mg/m2/day,3 days）; Other Names: Flu; Drug: Thymoglobulin; Thymoglobulin（2.5 mg/kg/day,4 days）; Other Names: ATG; Drug: Mycophenolate mofetil; Mycophenolate mofetil（0.25g/day）; Other Names: MMF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	2-years overall survival	2 years
Thalassemia-free survival	2-years thalassemia-free survival	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Engraftment	Myeloid engraftment at day +30	30 days
Cumulative Incidence of chronic Graft Versus Host Disease	Chronic graft versus host disease by 2 years	2 years
Cumulative Incidence of Infectious Complications	Cumulative incidence of bacterial, fungal and viral infections by 2 years	2 years
Transplant Related Mortality	Transplant-related mortality by 2 year	2 year
Cumulative Incidence of acute Graft Versus Host Disease	Acute graft versus host disease at day +100	100 days

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Guangxi Medical University
• Collaborators: Liuzhou Workers Hospital; Peking University People's Hospital; Ruijin Hospital; Xinqiao Hospital of Chongqing; Guilin Medical College; Hainan People's Hospital; The First People's Hospital of Yunnan; LiuZhou People's Hospital; Maoming People's Hospital; Red Cross Hospital of Yulin City; The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army; Affiliated Hospital of Youjiang University of Ethnic Medicine; Wuzhou People's Hospital; Guangxi Autonomous Region People's Hospital; The 920th Hospital of Joint Logistics Support Force of People's Liberation Army
• Investigators: Principal Investigator: Yongrong Lai, MD, First Affiliated Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2019
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; thalassemia major
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Reproductive Control Agents; Antitubercular Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Antibiotics, Antitubercular; Calcineurin Inhibitors; Cyclophosphamide; Fludarabine; Methotrexate; Tacrolimus; Mycophenolic Acid; Busulfan; Thymoglobulin; Cyclosporine; Cyclosporins
• Other Study ID Numbers: GX-HSCT-MT 2019

Drug and device information, study documents

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