A Prospective, Open-label, Randomized Controlled, Multicenter Clinical Study of Haplo-HSCT Using a TBI or TMLI Conditioning Regimen for Pediatric ALL

A Prospective, Open-label, Randomized Controlled, Multicenter Clinical Study of Haploidentical Hematopoietic Stem Cell Transplantation Using a TBI or TMLI Conditioning Regimen for Pediatric Acute Lymphoblastic Leukemia

This study aims to compare the effects of two different conditioning regimens on patients with acute lymphoblastic leukemia (ALL) undergoing haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT): Total Body Irradiation (TBI) and Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI). Both regimens are supported and recommended by literature; however, there is no definitive evidence favoring one over the other. We hypothesize that the TMLI regimen, compared to the TBI regimen, may more effectively eliminate leukemia cells in the bone marrow and lymphoid tissues, thereby reducing the risk of relapse, while also minimizing damage to normal tissues, thus reducing conditioning-related toxicity and transplant-related mortality. This study aims to provide evidence for the optimal conditioning regimen for haplo-HSCT in pediatric ALL patients, with the goal of improving patient quality of life and survival outcomes.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, Pediatric
• Intervention / Treatment: Drug: Cyclophosphamide; Radiation: TMLI; Radiation: TBI

• Study Type: Interventional
• Enrollment (Estimated): 276
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhilei Bian, PhD.; Phone Number: +86037166862278; Email: bianzhilei@sina.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450001
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Wan Xiangbo Xiangbo Wan; Phone Number: 86-037167963114; Email: wanbo@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Informed Consent: Participants or guardians must voluntarily sign a written informed consent form.
2. Age and Gender: Participants should be male or female, aged 1-17 years, inclusive.
3. Diagnosis: Participants must be diagnosed with acute lymphoblastic leukemia (ALL) according to World Health Organization (WHO) criteria, and the diagnosis must apply to pediatrics aged 1-17 years.
4. Remission Status: The participant's leukemia must be in hematologic remission (complete remission, CR) prior to transplantation.
5. Donor Availability: There must be a suitable haploidentical donor available, and the participant must consent to undergo haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

6. Karnofsky Performance Status: The participant must have a Karnofsky score of 70 or higher, indicating that they are capable of caring for themselves and carrying out normal activities. Additionally, they must not have significant organ dysfunction, defined by the following:

   • Cardiac Function: New York Heart Association (NYHA) classification of class II or lower.
   • Liver Function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be no more than 2.5 times the upper limit of normal. Bilirubin levels should be no more than 2 times the upper limit of normal.
   • Renal Function: Serum creatinine levels should be no more than 1.5 times the upper limit of normal, or the creatinine clearance rate should be at least 60 ml/min.
   • Pulmonary Function: Participants should not experience significant dyspnea, should not require oxygen therapy, should not have interstitial lung disease, and should not have any active pulmonary infections.

Exclusion Criteria:

To be eligible for inclusion in the study, participants must not meet any of the following criteria:

1. The patient has not achieved hematologic remission before transplantation.
2. The patient has chosen a non-haploidentical related donor.
3. The patient has severe cardiac, hepatic, renal, or pulmonary diseases that make them unable to tolerate the conditioning regimen.
4. The patient has an active or refractory infection, or other life-threatening complications.
5. The patient has a history of other malignant tumors, psychiatric disorders, or HIV infection.
6. The patients or guardians refuses to sign the informed consent form, is unwilling to comply with clinical follow-up required by the study, or does not consent to the use of their data to support future research, project presentations, and clinical practices.
7. The investigator deems the patient unsuitable for participation in the study for any other reason.

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: TMLI conditioning group; Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI) plus Cyclophosphamide	Drug: Cyclophosphamide; The total dose of cyclophosphamide is 120 mg/kg, administered over 2 days on days -4 and -3.; Other Names: CTX; Radiation: TMLI; The total dose of TMLI is 12 Gy, administered on days -7, -6, and -5, with 2 Gy per fraction, twice daily, for a total of 6 fractions.
Active Comparator: TBI conditioning group; Total Body Irradiation (TBI) plus Cyclophosphamide	Drug: Cyclophosphamide; The total dose of cyclophosphamide is 120 mg/kg, administered over 2 days on days -4 and -3.; Other Names: CTX; Radiation: TBI; The total dose of TBI is 12 Gy, administered on days -7, -6, and -5, with 2 Gy per fraction, twice daily, for a total of 6 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS)	RFS is defined as the time from transplantation to the first relapse or death, with RFS is defined as the time from transplantation to the first relapse or death, with the date of the last follow-up as the endpoint.	2 years
acute Graft Versus Host Disease (aGVHD)	The incidence of aGVHD within 100 days post-transplant.	100 days
Overall Survival (OS)	OS is defined as the time from transplantation to death, with the date of the last follow-up as the endpoint.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transplantation Related Mortality (TRM)	The incidence of TRM in 2 years.	100 days
Relapse Rate (RR)	The incidence ratio of leukemia relapse in 2 years.	2 years
Conditioning-related Adverse Events (CRAE)	Based on CTCAE v5.0.	30 days

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Xiangbo Wan, PhD., The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Estimated): March 17, 2025
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 16, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: 2024-KY-0212

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
• product manufactured in and exported from the U.S.: Yes