Low Dose Treosulfan Based Conditioning Regimen and PTCy in HSCT for Nijmegen Breakage Syndrome

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status and phase: Enrolling; Phase 2

Conditions: Nijmegen Breakage Syndrome

Treatments: Drug: Treosulfan

Study type: Interventional

Funder types: Other

Identifiers

NCT06198842

Treo-NBS 2023

Details and patient eligibility

About

The aim of the current study is to evaluate the safety and efficacy of low dose treosulfan based conditioning regimen in HSCT with post-transplant cyclophosphamide in Nijmegen breakage syndrome

Full description

Nijmegen breakage syndrome (NBS) is a DNA repair disorder. The only curative option for combine immunodeficiency in NBS is allogeneic hematopoietic stem cell transplantation (HSCT). Standard myeloablative conditioning regimens in DNA repair disorders lead to increased morbidity and mortality after HSCT. Low doses of alkylators are used to reduce toxicity rates, which, however, increase the risks of mixed chimerism and graft failure. The data of treosulfan usage in NBS are sparse. To evaluate the safety and efficacy of low dose treosulfan based conditioning regimen in NBS, treosulfan 21g/m2 in combination with fludarabine 150mg/mg, thymoglobulin (Genzyme) 5mg/kg and rituximab 100mg/m2 will be used from day -6 to -1 day, followed by stem cell infusion and post-transplant cyclophosphamide 25mg/kg/day (+3,+4 day) for GVHD prophylaxis. The primary endpoint is event-free survival, where graft failure, death, and malignancies are considered as events.

Enrollment: 10 estimated patients

Sex: All

Ages: 3 months to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Patients aged ≥ 3 months and < 21 years
2. Patients diagnosed with NBS eligible for an allogeneic HSCT
3. Signed written informed consent signed by a parent or legal guardian

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

intervention/treatment

Experimental group

Description:

Fludarabine 150mg/m2 (days -6, -5, -4, -3, -2) Treosulfan 21g/m2 (days -6, -5, -4) Thymoglobulin (Genzyme) 5mg/kg (days -5, -4) Rituximab 100mg/m2 (day -1) Cyclophosphamide 50mg/kg (days +3, +4)

Treatment:

Drug: Treosulfan