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

Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology (Other)

Overall Status

Recruiting

CT.gov ID

NCT04400045

Collaborator

(none)

Enrollment

Location

Arm

35.3

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Nijmegen Breakage Syndrome	Drug: Treosulfan	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 22, 2020

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: intervention/treatment 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 Treosulfan 21mg/m2 (days -6, -5, -4)

Arm

Intervention/Treatment

Experimental: intervention/treatment

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

Treosulfan 21mg/m2 (days -6, -5, -4)

Outcome Measures

Primary Outcome Measures

Event-free survival [3 years after HSCT]
Events: graft failure, death, malignancies

Secondary Outcome Measures

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 [3 years]
malignancies, non-malignant complications

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HSCT department	Moscow		Russian Federation	117198

Sponsors and Collaborators

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

ClinicalTrials.gov Identifier:

NCT04400045

Other Study ID Numbers:

NCPHOI-2020-04

First Posted:

May 22, 2020

Last Update Posted:

Jun 25, 2020

Last Verified:

Jun 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Nijmegen Breakage Syndrome

Syndrome

Treosulfan

Study Results

No Results Posted as of Jun 25, 2020