BuCy Vs. TBICy for Allo-HSCT in T-ALL Patients

Soochow University

Status and phase: Not yet enrolling; Phase 3

Conditions: Total Body Irradiation; Chemotherapy; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; T-Cell Lymphocytic Leukemia

Treatments: Biological: BuCy; Biological: TBICy

Study type: Interventional

Funder types: Other

Identifiers

NCT06673459

TREAL1

Details and patient eligibility

About

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.

Enrollment: 430 estimated patients

Sex: All

Ages: 2 to 55 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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430 participants in 2 patient groups

TBICy

Experimental group

Description:

Patients enrolled in this arm will receive total body irradiation plus cyclophosphamide as conditioning regimen.

Treatment:

Biological: TBICy

BuCy

Active Comparator group

Description:

Patients enrolled in this arm will receive busulfan plus cyclophosphamide as conditioning regimen.

Treatment:

Biological: BuCy