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PTCy and and Ruxolitinib for GVHD Prophylaxis After HSCT With Thymoglobulin in Conditioning Regimen in Patients With Inborn Errors of Immunity

Phase 2
Recruiting
Conditions
Inborn Errors of Immunity
Interventions
Registration Number
NCT06199427
Lead Sponsor
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
intervention/treatmentCyclophosphamideConditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, thymoglobulin 5 mg/kg and thiotepa 10 mg/kg or melphalan 140 mg/m2 GVHD prophylaxis regimen for matched unrelated (MUD) and matched related donors (MRD): Cyclophosphamide (PTCY) 25 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5 GVHD prophylaxis regimen for mismatched related donor (MMRD): Cyclophosphamide (PTCY) 50 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5
intervention/treatmentRuxolitinibConditioning regimen containing treosulfan 30-42 g/m2, fludarabine 150 mg/mg, thymoglobulin 5 mg/kg and thiotepa 10 mg/kg or melphalan 140 mg/m2 GVHD prophylaxis regimen for matched unrelated (MUD) and matched related donors (MRD): Cyclophosphamide (PTCY) 25 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5 GVHD prophylaxis regimen for mismatched related donor (MMRD): Cyclophosphamide (PTCY) 50 mg/kg/day (days +3, +4) Ruxolitinib 7 mg/m2 from day +5
Primary Outcome Measures
NameTimeMethod
Event-free survival1 year after HSCT

Events: graft failure, death

Secondary Outcome Measures
NameTimeMethod
Cumulative incidence of acute graft versus host disease1 year after HSCT
Cumulative incidence of transplant related mortality1 year after HSCT
Cumulative incidence of chronic graft versus host disease1 year after HSCT
Incidence of early organ toxicity100 days
Overall survival1 year after HSCT
Cumulative incidence of engraftment100 days
Cumulative incidence of graft failure1 year after HSCT
Cumulative incidence of viral infections1 year after HSCT
Investigation of the concentration of ruxolitinib in the blood To investigate the pharmacokinetics of ruxolitinib1 month after HSCT

The features of pharmacokinetics in children of different ages

Trial Locations

Locations (1)

HSCT department

🇷🇺

Moscow, Russian Federation

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