NCT07366801

Co-infusion of Treg-enriched Donor Lymphocytes With CD3-depleted Hematopoietic Stem Cell Graft to Prevent Graft-versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation Among Children With Hematologic Malignancies

Pilot Study of Co-Infusion of Donor Lymphocytes Enriched With Regulatory T Lymphocytes With Ex-vivo CD3-Depleted Hematopoietic Stem Cell Graft for the Prevention of Graft-versus-Host Disease in Children With Hematopoietic and Lymphoid Tissue Neoplasms

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 64 (estimated)
• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology · Academic / Other
• Sex: All
• Age: 1 Year – 25 Years
• Healthy volunteers: Not accepted

Summary

Two key methods of GVHD prevention in allogeneic HSCT have a number of limitations: ex vivo T depletion is associated with an excess of infectious complications, and pharmacological immunosuppression with insufficient efficacy of GVHD prevention. Modern graft engineering technologies make it possible to create a graft with a balanced cell composition, reducing the risk of adverse events, in particular, severe forms of acute and chronic GVHD, while preserving the immunological function of the graft. In the proposed concept, enrichment of the T graft with regulatory cells will reduce the risk of GVHD and preserve a sufficient number of T lymphocytes in the graft for the formation of protective anti-infective immunity in the early stages after HSCT. The combination of partial T depletion and pharmacological immunosuppression minimized in volume and duration will combine the advantages of T depletion (early engraftment, low risk of GVHD, low risk of organ complications) and pharmacological prophylaxis (restoration of anti-infective immunity).

Detailed description

1. Infusion of ex-vivo T-depleted peripheral blood hematopoietic stem cells (CD3 depletion product) 2. Infusion of donor lymphocytes enriched with T regulatory lymphocytes (CD25 selective product) 3. Drug therapy (pharmacological prophylaxis of GVHD) * Cyclosporine A * Sirolimus o Ruxolitinib o Abatacept

Conditions

• Acute Myeloid Leukemia, Relapsed
• Acute Lymphoblastic Leukemia, High Risk
• Acute Myeloid Leukemia, High Risk
• Acute Lymphoblastic Leukemia, Relapse

Interventions

Type	Name	Description
DRUG	Cyclosporine A (CsA)	The combination of partial T depletion and pharmacological immunosuppression minimized in volume and duration will combine the advantages of T depletion (early engraftment, low risk of GVHD, low risk of organ complications) and pharmacological prophylaxis (restoration of anti-infective immunity).
DRUG	Sirolimus	Pharmacological prophylaxis of GVHD is one of the key subjects of evaluation in the current study. Since the optimal pharmacological approach is not known, the allocation of the patients to study groups will be by randomization procedure, although not for the purpose of direct comparison, but for unbiased descriptive analysis. There will be four main groups and an additional group to be open for allocation based on the main group closing for fitting the stopping rules. The details of pharmacological GVHD prevention are Sirolimus 1 mg -3 till +30 4-8 ng/ml
DRUG	Ruxolitinib (JAKAVI®)	Pharmacological prophylaxis of GVHD is one of the key subjects of evaluation in the current study. Since the optimal pharmacological approach is not known, the allocation of the patients to study groups will be by randomization procedure, although not for the purpose of direct comparison, but for unbiased descriptive analysis. There will be four main groups and an additional group to be open for allocation based on the main group closing for fitting the stopping rules. The details of pharmacological GVHD prevention regimens are Ruxolitinib 5 mg -2 till +30
DRUG	Abatacept	Pharmacological prophylaxis of GVHD is one of the key subjects of evaluation in the current study. Since the optimal pharmacological approach is not known, the allocation of the patients to study groups will be by randomization procedure, although not for the purpose of direct comparison, but for unbiased descriptive analysis. There will be four main groups and an additional group to be open for allocation based on the main group closing for fitting the stopping rules. Abatacept 10 mg/kg -1, +7, +14, +28

Timeline

• Start date: 2025-09-03
• Primary completion: 2027-06-01
• Completion: 2028-02-03
• First posted: 2026-01-26
• Last updated: 2026-01-26

Locations

1 site across 1 country: Russia