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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Open-label Phase 2 Study of Low Dose Treosulfan Based Conditioning Regimen Efficacy in Hematopoietic Stem Cell Transplantation for Children With Nijmegen Breakage Syndrome

Conditions
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Nijmegen Breakage Syndrome

Intervention / Treatment
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* Drug: Treosulfan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 3 months and < 21 years Patients diagnosed with NBS eligible for an allogeneic HSCT Signed written informed consent signed by a parent or legal guardian

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention/treatment<br>Fludarabine 150mg/m2 (days -6, -5, -4, -3, -2) Treosulfan 21g/m2 (days -6, -5, -4) Cyclophosphamide 40mg/kg (days -3, -2) Thymoglobulin (Genzyme) 5mg/kg (days -5, -4) Rituximab 100mg/m2 (day -1) Stem cell infusion - day 0 | Drug: Treosulfan<br>* Treosulfan 21mg/m2 (days -6, -5, -4)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | Events: graft failure, death, malignancies | 3 years after HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 3 years after HSCT | 
| 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 | 
| Cumulative incidence of chronic graft versus host disease |  | 3 years | 
| Incidence of early organ toxicity |  | 100 days | 
| Cumulative incidence of transplant related mortality |  | 3 years | 
| Incidence of long-term toxicity | malignancies, non-malignant complications | 3 years |