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

Phase 2

• Conditions: Nijmegen Breakage Syndrome
• Interventions: Drug: Treosulfan

• Registration Number: NCT04400045
• Lead Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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.

Study Timeline

• Study First Submitted: 2020-05-19
• Study First Submitted QC: 2020-05-19
• Study Start: 2020-05-22
• Study First Posted: 2020-05-22
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-23
• Last Update Posted: 2020-06-25
• Primary Completion: 2023-05
• Study Completion: 2023-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
intervention/treatment	Treosulfan	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

Primary Outcome Measures

Name	Time	Method
Event-free survival	3 years after HSCT	Events: graft failure, death, malignancies

Secondary Outcome Measures

Name	Time	Method
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
Cumulative incidence of acute graft versus host disease	1 year
Cumulative incidence of engraftment	100 days
Incidence of long-term toxicity	3 years	malignancies, non-malignant complications
Overall survival	3 years after HSCT
Cumulative incidence of graft failure	3 years
Cumulative incidence of viral infections	1 year

Trial Locations

Locations (1)

HSCT department; 🇷🇺 Moscow, Russian Federation