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

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Acute Lymphoblastic Leukemia, Relapse; Acute Myeloid Leukemia, High Risk; Acute Lymphoblastic Leukemia, High Risk; Acute Myeloid Leukemia, Relapsed

Treatments: Drug: Abatacept; Drug: Cyclosporine A (CsA); Drug: Ruxolitinib (JAKAVI®); Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT07366801

NCHPOI- 2025-14

Details and patient eligibility

About

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).

Full 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

Enrollment: 64 estimated patients

Sex: All

Ages: 1 to 25 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Informed consent signed by the patient (age 14 to 25 years) and/or his/her legal representative (age 0 to 18 years).
2. The patient has an indication for allogeneic hematopoietic stem cell transplantation (HSCT) established in accordance with the current regulatory framework
3. Planned HSCT from a haploidentical donor
4. The Karnofsky or Lansky score is more than 70%
5. Life expectancy of at least 8 weeks
6. Heart function: ejection fraction of at least 40%
7. Consent to continue follow-up for 3 years

Exclusion criteria

1. Acute viral hepatitis or acute HIV infection
2. Hypoxemia with SaO2 <90%
3. Bilirubin >3 normal
4. Creatinine >3 norms
5. Pregnancy and lactation
6. Life-threatening infection
7. Severe (>?) pathology of the central nervous system (epilepsy, dementia, organic damage to the central nervous system)
8. Karnofsky score or Lansky score <70%

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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64 participants in 4 patient groups

Cyclosporine A

Active Comparator group

Description:

Four groups corresponding to the pharmacological prophylaxis of GVHD: 1) Cyclosporine A

Treatment:

Drug: Cyclosporine A (CsA)

Sirolimus

Active Comparator group

Description:

Drug therapy (pharmacological prophylaxis of GVHD) 2) Sirolimus

Treatment:

Drug: Sirolimus

Ruxolitinib

Active Comparator group

Description:

Drug therapy (pharmacological prophylaxis of GVHD) Ruxolitinib

Treatment:

Drug: Ruxolitinib (JAKAVI®)

Abatacept

Active Comparator group

Description:

Drug therapy (pharmacological prophylaxis of GVHD) Abatacept

Treatment:

Drug: Abatacept