Study of Treosulfan-Based Conditioning for HSCT in Nijmegen Breakage Syndrome

Официальное название

A Clinical Study of the Efficacy and Safety of Conditioning With Low Doses of Treosulfan Before Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Nijmegen Breakage Syndrome

Обзор

Nijmegen breakage syndrome is one of the DNA repair defect disorders. A characteristic feature of these syndromes is a predisposition to the development of malignant neoplasms. The only curative option for the combined immunodeficiency in Nijmegen breakage syndrome is allogeneic hematopoietic stem cell transplantation (HSCT). In addition to correcting the immunodeficiency, HSCT can reduce the risk of developing hematopoietic tumors. Due to the increased sensitivity of cells in patients with Nijmegen breakage syndrome to alkylating drugs, the use of standard myeloablative conditioning regimens for this disease significantly increases the risks of toxic complications and transplant-related mortality. Treosulfan is an alkylating agent that has demonstrated efficacy with comparatively low risks of toxic complications when used as part of conditioning prior to allogeneic HSCT for various diseases in patients of all age groups. There is currently experience using treosulfan in patients with Nijmegen breakage syndrome at reduced doses (21 and 30 g/m²). However, a number of questions remain unresolved. Based on our previous experience, a dose of 21 g/m² is sufficient for patients with Nijmegen breakage syndrome without a malignant disease, as it ensures good graft function (a high probability of full donor chimerism and control of the immunodeficiency). At the same time, there is reason to believe that this dose is insufficient to provide an antitumor effect from the conditioning. We are planning a multicenter study to investigate treosulfan-based conditioning in patients with Nijmegen breakage syndrome, which will stratify patients based on the presence or absence of malignant disease. Patients without a tumor will receive treosulfan at a dose of 21 g/m², and patients with a tumor will receive 30 g/m².

Вмешательства

• Препарат Treosulfan (Treo)
  We are planning a multicenter study to investigate treosulfan-based conditioning in patients with Nijmegen breakage syndrome, which will stratify patients based on the presence or absence of malignant disease. Patients without a tumor will receive treosulfan at a dose of 21 g/m², and patients with a tumor will receive 30 g/m²

Первичные конечные точки

• To evaluate event-free survival (EFS), defined by the occurrence of death, graft rejection, or development of secondary malignancy/relapse. [Срок оценки: 2 years]

Вторичные конечные точки (8)

• Overall survival [Срок оценки: 2 years]
• To evaluate the rate of transplant-associated mortality. [Срок оценки: 2 years]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [Срок оценки: 3 months]
• Probability of graft rejection [Срок оценки: 2 years]
• Frequency of Complete Donor and Mixed Chimerism after HSCT [Срок оценки: 1 year]
• Incidence of acute GVHD. [Срок оценки: 1 year]
• Incidence of chronic GVHD. [Срок оценки: 2 years]
• To assess the kinetics of immune reconstitution [Срок оценки: 1 year]

Критерии участия

Критерии включения

• genetically confirmed Nijmegen breakage syndrome
• availability of informed consent for study participation, signed by the patient (ages 14 to 21) and/or their legal representative (ages 0 to 18).
• absence of contraindications to HSCT based on the patient's somatic status.

Критерии исключения

• other DNA repair deficiency syndromes (both specified and unspecified)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07316595 · NCHPOI- 2025-9

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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