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

NCT06559345 | Recruiting Phase 2

• 1 other identifier: 2024-KY-0212
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia, Pediatric

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Transplantation Related Mortality (TRM)

  100 days

• Relapse Rate (RR)

  2 years

• Conditioning-related Adverse Events (CRAE)

  30 days

Study Arms (2)

TMLI conditioning group

EXPERIMENTAL

Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI) plus Cyclophosphamide

Radiation: TMLI; Drug: Cyclophosphamide

TBI conditioning group

ACTIVE COMPARATOR

Total Body Irradiation (TBI) plus Cyclophosphamide

Radiation: TBI; Drug: Cyclophosphamide

Interventions

TMLI RADIATION

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.

TMLI conditioning group

TBI RADIATION

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.

TBI conditioning group

Cyclophosphamide DRUG

The total dose of cyclophosphamide is 120 mg/kg, administered over 2 days on days -4 and -3.

Also known as: CTX

TBI conditioning group; TMLI conditioning group

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Informed Consent: Participants or guardians must voluntarily sign a written informed consent form.
• Age and Gender: Participants should be male or female, aged 1-17 years, inclusive.
• 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.
• Remission Status: The participant's leukemia must be in hematologic remission (complete remission, CR) prior to transplantation.
• Donor Availability: There must be a suitable haploidentical donor available, and the participant must consent to undergo haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
• 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.

You may not qualify if:

• The patient has not achieved hematologic remission before transplantation.
• The patient has chosen a non-haploidentical related donor.
• The patient has severe cardiac, hepatic, renal, or pulmonary diseases that make them unable to tolerate the conditioning regimen.
• The patient has an active or refractory infection, or other life-threatening complications.
• The patient has a history of other malignant tumors, psychiatric disorders, or HIV infection.
• 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.
• The investigator deems the patient unsuitable for participation in the study for any other reason.

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University: lead

Study Sites (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450001, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Xiangbo Wan, PhD.

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhilei Bian, PhD.

CONTACT

+86037166862278; bianzhilei@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: August 19, 2024
• Study Start: March 17, 2025
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: February 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)