Clinical trial NCT06199427: PTCy and and Ruxolitinib for GVHD Prophylaxis After HSCT With Thymoglobulin in Conditioning Regimen in Patients With Inborn Errors of Immunity
Official title: Safety and Efficacy of Cyclophosphamide and Ruxolitinib for Graft-versus-host-disease Prophylaxis After Hematopoietic Stem Cell Transplantation With Thymoglobulin Serotherapy in Conditioning Regimen in Patients With Inborn Errors of Immunity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Inborn Errors of Immunity
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
First posted: 2024-01-10
Enrollment: 100
Sex: ALL
Minimum age (years): 0
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Event-free survival
timeFrame: 1 year after HSCT
Secondary outcomes:
measure: Overall survival
timeFrame: 1 year after HSCT
measure: Cumulative incidence of acute graft versus host disease
timeFrame: 1 year after HSCT
measure: Cumulative incidence of chronic graft versus host disease
timeFrame: 1 year after HSCT
measure: Cumulative incidence of engraftment
timeFrame: 100 days
measure: Cumulative incidence of graft failure
timeFrame: 1 year after HSCT
measure: Incidence of early organ toxicity
timeFrame: 100 days
measure: Cumulative incidence of transplant related mortality
timeFrame: 1 year after HSCT
measure: Cumulative incidence of viral infections
timeFrame: 1 year after HSCT
measure: Investigation of the concentration of ruxolitinib in the blood To investigate the pharmacokinetics of ruxolitinib
timeFrame: 1 month after HSCT
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: HSCT department
Study officials:
affiliation: National Research Center for Pediatric Hematology, Moscow, Russia
name: Dmitry Balashov, MD, PhD
role: STUDY_CHAIR
References: