Nijmegen Breakage Syndrome
Conditions
Brief summary
The aim of the current study is to evaluate the safety and efficacy of low dose treosulfan based conditioning regimen in HSCT in Nijmegen breakage syndrome
Detailed 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, cyclophosphamide 40mg/kg, thymoglobulin (Genzyme) 5mg/kg and rituximab 100mg/m2 will be used from day -6 to -1 day, followed by stem cell infusion. The primary endpoint is event-free survival, where graft failure, death, and malignancies are considered as events.
Interventions
DRUGTreosulfan
Treosulfan 21mg/m2 (days -6, -5, -4)
Sponsors
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | 3 years after HSCT | Events: graft failure, death, malignancies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of engraftment | 100 days | — |
| Cumulative incidence of graft failure | 3 years | — |
| Cumulative incidence of viral infections | 1 year | — |
| Cumulative incidence of acute graft versus host disease | 1 year | — |
| Overall survival | 3 years after HSCT | — |
| Incidence of early organ toxicity | 100 days | — |
| Cumulative incidence of transplant related mortality | 3 years | — |
| Incidence of long-term toxicity | 3 years | malignancies, non-malignant complications |
| Cumulative incidence of chronic graft versus host disease | 3 years | — |
Countries
Russia
Contacts
Primary ContactDmitry Balashov, MD, PhD
Backup ContactAlexandra Laberko, MD
Outcome results
None listed