Inborn Errors of Immunity
Conditions
Brief summary
The aim of the current study is to evaluate the efficacy of combined regimen of GVHD prophylaxis with thymoglobulin in conditioning regimen and PTCY with ruxolitinib used after HSCT in patients with inborn errors of immunity (IEI)
Detailed description
Hematopoietic stem cell transplantation (HSCT) is widely used in inborn errors of immunity (IEI), and risks of graft-versus-host disease (GVHD) remain high. Use of post-transplant cyclophosphamide (PTCY) for GVHD prophylaxis revolutionized the outcomes of HSCT from mismatched related donor (MMRD). Use of ruxolitinib for GVHD prophylaxis demonstrates promising results in adult patients. Another well-known option for GVHD prevention is antithymocyte globulin. To evaluate the efficacy of combination of thymoglobulin with PTCY and ruxolitinib for GVHD prophylaxis, conditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, and thiotepa 10 mg/kg or melphalan 140 mg/m2 and GVHD prophylaxis regimen containing cyclophosphamide 50 mg/kg for MMRD, 25 mg/kg for matched unrelated and related donors at days +3, 4 post-HSCT and ruxolitinib at dose 7 mg/m2 from day +5 after HSCT will be used in patients with IEI.
Interventions
DRUGCyclophosphamide
Cyclophosphamide 25mg/kg (days +3, +4) after HSCT from MUD and MRD Cyclophosphamide 50mg/kg (days +3, +4) after HSCT from MMRD
DRUGRuxolitinib
Ruxolitinib 7 mg/m2 from day +5 after HSCT
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
0 Months to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥ 0 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
Concomitant severe somatic disease associated with an additional risk of severe complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | 1 year after HSCT | Events: graft failure, death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of acute graft versus host disease | 1 year after HSCT | — |
| Cumulative incidence of chronic graft versus host disease | 1 year after HSCT | — |
| Cumulative incidence of engraftment | 100 days | — |
| Cumulative incidence of graft failure | 1 year after HSCT | — |
| Overall survival | 1 year after HSCT | — |
| Cumulative incidence of transplant related mortality | 1 year after HSCT | — |
| Cumulative incidence of viral infections | 1 year after HSCT | — |
| Investigation of the concentration of ruxolitinib in the blood To investigate the pharmacokinetics of ruxolitinib | 1 month after HSCT | The features of pharmacokinetics in children of different ages |
| Incidence of early organ toxicity | 100 days | — |
Countries
Russia
Contacts
Primary ContactDmitry Balashov, MD, PhD
Backup ContactAlexandra Laberko, MD, PhD
Outcome results
None listed