Clinical trial NCT06673459: BuCy Vs. TBICy for Allo-HSCT in T-ALL Patients
Official title: Busulfan Plus Cyclophosphamide Vs. Total Body Irradiation Plus Cyclophosphamide for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute T Lymphoblastic Leukemia: a Randomized Controlled, Open-label, Multi-center Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: T-Cell Lymphocytic Leukemia
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Total Body Irradiation
Chemotherapy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Soochow University
name: Ruijin Hospital
name: Nanfang Hospital, Southern Medical University
name: Fujian Medical University Union Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: Wuhan Union Hospital, China
name: Zhejiang University
name: Anhui Provincial Hospital
First posted: 2024-11-05
Enrollment: 430
Sex: ALL
Minimum age (years): 2
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: T-cell acute lymphoblastic leukemia (T-ALL), a hematological malignant neoplasm of immature T cells, accounting for a morbidity of 10-15% among pediatric and 20-25% among adult patients of ALL. Despite the application of improved intensive therapies, the overall survival (OS) of T-ALL patients is still unsatisfactory, with a 5-year OS rate of less than 60% in adults and 85% in children. Over the past few decades, allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has emerged as a potential and the most likely curative treatment for patients with high-risk hematological malignant neoplasms, and it has been proven that allo-HSCT could hold the potential to improve the prognosis of T-ALL patients and may even cure T-ALL.

The two most common myeloablative conditioning regimens for T-ALL patients with allo-HSCT were total body irradiation (TBI) plus cyclophosphamide (TBI-Cy) and busulfan (Bu) plus cyclophosphamide (BuCy). The most common use conditioning regimen for ALL patients is the TBI-Cy conditioning regimen over other hematological malignancy patients because TBI possess potent and distinct anti-leukemic effects, particularly in organs not easily affected by systemic chemotherapy and intense immunosuppressive effects. However, TBI-based conditioning regimens may cause a high risk of cataracts, interstitial pneumonitis (IP), engraftment failure and even subsequent malignant neoplasms (SMNs). To avoid these disadvantages, intravenous Bu replaced TBI as a part of conditioning.

Extensive studies have shown that allo-HSCT with conditioning regimens based on TBI could benefit survival compared with conditioning regimens based on chemotheraphy in treating ALL. We retrospectively analyzed post-10-year data from T-ALL patients from two transplant centers, and all the databases were used to eliminate confounding factors via PSM. We demonstrated that the TBI-Cy conditioning regimen had inferior efficacy to the BuCy conditioning regimen, especially for T-ALL patients who were children, refractory, had extramedullary disease before transplantation, had active disease or an MRD-positive status at allo-HSCT, or who received haplo-HSCT.


Eligibility criteria: Inclusion Criteria:

1. T-ALL patients aged \> 2 years and ≤55 years;
2. For the first time accept allo-HSCT;
3. With Eastern Cooperative Oncology Group (ECOG) performance status of 0-3; 4. Signing an informed consent form, having the ability to comply with study and follow-up procedures.

Exclusion Criteria:

1. With other malignancies;
2. With a previous history of autologous hematopoietic cell transplantation, allogeneic hematopoietic cell transplantation or chimeric antigen receptor T cell therapy;
3. With uncontrolled infection intolerant to haploidentical hematopoietic cell transplantation;
4. With severe organ dysfunction;
5. In pregnancy or lactation period;
6. With any conditions not suitable for the trial (investigators' decision).

Primary outcomes:
measure: Progression-free survival
timeFrame: 2 years after randomization
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years after randomization
measure: Cumulative incidence of relapse
timeFrame: 2 years after randomization
measure: Non-relapse mortality
timeFrame: 2 years after randomization
measure: Adverse events
timeFrame: 2 years after randomization
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: