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

Phase 2

Recruiting

• Conditions: Acute Lymphoblastic Leukemia, Pediatric
• Interventions: Radiation: TBI; Radiation: TMLI; Drug: Cyclophosphamide

• Registration Number: NCT06564493
• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University

Brief Summary

This study aims to compare the effects of two different conditioning regimens on patients with acute lymphoblastic leukemia (ALL) undergoing matched sibling donor hematopoietic stem cell transplantation (MSD-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 MSD-HSCT in pediatric ALL patients, with the goal of improving patient quality of life and survival outcomes.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-04
• Study First Submitted QC: 2024-08-19
• Study First Posted: 2024-08-21
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-16
• Last Update Posted: 2025-02-18
• Study Start: 2025-03-01
• Primary Completion: 2029-07-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 170

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 matched sibling donoravailable, and the participant must consent to undergo MSD hematopoietic stem cell transplantation (MSD-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. o 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-MSD donor.

2. The patient has severe cardiac, hepatic, renal, or pulmonary diseases that make them unable to tolerate the conditioning regimen.

3. The patient has an active or refractory infection, or other life-threatening complications.

4. The patient has a history of other malignant tumors, psychiatric disorders, or HIV infection.

5. 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.

6. The investigator deems the patient unsuitable for participation in the study for any other reason.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TBI conditioning group	TBI	Total Body Irradiation (TBI) plus Cyclophosphamide
TMLI conditioning group	TMLI	Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI) plus Cyclophosphamide
TMLI conditioning group	Cyclophosphamide	Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI) plus Cyclophosphamide
TBI conditioning group	Cyclophosphamide	Total Body Irradiation (TBI) plus Cyclophosphamide

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China