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

NCT07316595 | Not Yet Recruiting Phase 2

• 1 other identifier: NCHPOI- 2025-9
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

HSCT; Nijmegen Breakage Syndrome; Treosulfan Based Conditioning

Outcome Measures

Primary Outcomes (1)

• To evaluate event-free survival (EFS), defined by the occurrence of death, graft rejection, or development of secondary malignancy/relapse.

  Event-free survival in patients with Nijmegen syndrome is the primary criterion for assessing the effectiveness of HSCT. It was precisely the need to solve the problems of graft rejection, relapses of malignant diseases, and secondary tumors that became the main reasons for initiating this study.

  2 years

Secondary Outcomes (8)

• Overall survival

  2 years

• To evaluate the rate of transplant-associated mortality.

  2 years

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  3 months

• Probability of graft rejection

  2 years

• Frequency of Complete Donor and Mixed Chimerism after HSCT

  1 year

Study Arms (2)

Patients with Nijmegen breakage syndrome without malignant disease.

ACTIVE COMPARATOR

Drug: Treosulfan (Treo)

Patients with Nijmegen breakage syndrome and malignant disease.

ACTIVE COMPARATOR

Drug: Treosulfan (Treo)

Interventions

Treosulfan (Treo) DRUG

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

Patients with Nijmegen breakage syndrome and malignant disease.; Patients with Nijmegen breakage syndrome without malignant disease.

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead
• Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University: collaborator
• Regional Children's Clinical Hospital, Yekaterinburg: collaborator
• Morozov Children's Municipal Clinical Hospital of the Moscow City Health Department State-Financed H: collaborator
• Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation: collaborator

MeSH Terms

Conditions

Nijmegen Breakage Syndrome

Interventions

treosulfan

Condition Hierarchy (Ancestors)

DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Dmitry Balashov, MD, PhD

CONTACT

+7-926-579-78-17; bala8@yandex.ru

Alexandra Laberko, MD, PhD

CONTACT

+7-903-299-49-58; alexandra-lab@yandex.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We are planning a 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.

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: January 5, 2026
• Study Start: December 30, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share