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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

1 Year - 25 Years

Healthy Volunteers

Not accepted

Interventions

• Cyclosporine A (CsA) — DRUG
  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).
• Sirolimus — DRUG
  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
• Ruxolitinib (JAKAVI®) — DRUG
  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
• Abatacept — DRUG
  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

Study Details

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).

Key Dates

Start date

Sep 3, 2025

Status verified

Dec 2025

Primary completion

Jun 1, 2027

Completion

Feb 3, 2028

Study Design

Enrollment

64 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Active Comparator: Cyclosporine A
  Four groups corresponding to the pharmacological prophylaxis of GVHD: 1) Cyclosporine A
• Active Comparator: Sirolimus
  Drug therapy (pharmacological prophylaxis of GVHD) 2) Sirolimus
• Active Comparator: Ruxolitinib
  Drug therapy (pharmacological prophylaxis of GVHD) Ruxolitinib
• Active Comparator: Abatacept
  Drug therapy (pharmacological prophylaxis of GVHD) Abatacept

Primary Outcome Measure

Feasibility- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: day 30 ]

Central Contacts

• Michael Maschan, Prof
  +79166512145
  [email protected]