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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат TBICy
  The TBI-Cy group was administered 250 mg/m2/d oral Me-CCNU on day -8. A total of 12 Gy TBI was for each patient and fractionated dose was 2 Gy twice daily or 4Gy once daily on days -8 to -6. Occluding of the lung fields during TBI, the corresponding irradiation dose reduced to a total of 8 Gy. On day -5, the schedule was intravenous 2 g/m2 Ara-C every 12 hours. Then intravenous 1.8 g/m2 CTX once per day from days -4 to -3.
• Биопрепарат BuCy
  The BuCy group received oral Me-CCNU 250 mg/m2/d twice daily on day -8, intravenous cytosine arabinoside (Ara-C) 2 g/m2 twice daily on day -7, intravenous Bu 3.2 mg/kg/d from days -6 to -4, and intravenous cyclophosphamide (CTX) 1.8 g/m2/d from days -3 to -2. There were no patients accepted oral Bu.

Первичные конечные точки

• Progression-free survival [Срок оценки: 2 years after randomization]

Вторичные конечные точки (4)

• Overall survival [Срок оценки: 2 years after randomization]
• Cumulative incidence of relapse [Срок оценки: 2 years after randomization]
• Non-relapse mortality [Срок оценки: 2 years after randomization]
• Adverse events [Срок оценки: 2 years after randomization]

Критерии участия

Критерии включения

• T-ALL patients aged > 2 years and ≤55 years;
• For the first time accept allo-HSCT;
• 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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Soochow University — Сучжоу

Идентификаторы

NCT: NCT06673459 · TREAL1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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