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

Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age1-25
SponsorFederal Research Institute of Pediatric Hematology, Oncology and Immunology

About this trial

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).

Eligibility criteria

Qualifiers

Informed consent signed by the patient (age 14 to 25 years) and/or his/her legal representative (age 0 to 18 years).

The patient has an indication for allogeneic hematopoietic stem cell transplantation (HSCT) established in accordance with the current regulatory framework

Planned HSCT from a haploidentical donor

The Karnofsky or Lansky score is more than 70%

Disqualifiers

Acute viral hepatitis or acute HIV infection

Hypoxemia with SaO2 <90%

Bilirubin >3 normal

Creatinine >3 norms

Trial design

Treatments tested in this trial

  • Cyclosporine A (CsA)
  • Sirolimus
  • Ruxolitinib (JAKAVI®)
  • Abatacept

Treatment groups

64 Participants
are divided into 4 treatment groups