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

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status and phase: Not yet enrolling; Phase 2

Conditions: Treosulfan Based Conditioning; Nijmegen Breakage Syndrome; HSCT

Treatments: Drug: Treosulfan (Treo)

Study type: Interventional

Funder types: Other

Identifiers

NCT07316595

NCHPOI- 2025-9

Details and patient eligibility

About

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.

Enrollment: 24 estimated patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Patients with Nijmegen breakage syndrome without malignant disease.

Active Comparator group

Treatment:

Drug: Treosulfan (Treo)

Patients with Nijmegen breakage syndrome and malignant disease.

Active Comparator group

Treatment:

Drug: Treosulfan (Treo)