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

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status and phase: Enrolling; Phase 2

Conditions: Inborn Errors of Immunity

Treatments: Drug: Cyclophosphamide; Drug: Ruxolitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT06199427

IEI-PTCy 2023

Details and patient eligibility

About

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)

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

intervention/treatment

Experimental group

Description:

Conditioning 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

Treatment:

Drug: Cyclophosphamide

Drug: Ruxolitinib