Clinical trial NCT06559345: A Prospective, Open-label, Randomized Controlled, Multicenter Clinical Study of Haplo-HSCT Using a TBI or TMLI Conditioning Regimen for Pediatric ALL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia, Pediatric
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2024-08-19
Enrollment: 276
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Relapse-free survival (RFS)
timeFrame: 2 years
measure: acute Graft Versus Host Disease (aGVHD)
timeFrame: 100 days
measure: Overall Survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: Transplantation Related Mortality (TRM)
timeFrame: 100 days
measure: Relapse Rate (RR)
timeFrame: 2 years
measure: Conditioning-related Adverse Events (CRAE)
timeFrame: 30 days
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Xiangbo Wan, PhD.
role: PRINCIPAL_INVESTIGATOR
References: