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

Официальное название

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

Обзор

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).

Подробное описание

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

Вмешательства

• Препарат 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).
• Препарат 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 pharmacolog
• Препарат 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 pharmacolog
• Препарат 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,

Первичные конечные точки

• Feasibility- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Срок оценки: day 30]
• Safety- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Срок оценки: 120 days after HSCT]

Вторичные конечные точки (10)

• Cumulative probability of engraftment [Срок оценки: up to 100 day]
• Time to engraftment of neutrophils and platelets [Срок оценки: 100 day after HSCT]
• Cumulative risk of acute GVHD Grade II-IV [Срок оценки: up to 100 days after HSCT]
• Cumulative risk of viral [Срок оценки: at 120 day after HSCT]
• cumulative risk of developing severe chronic GVHD [Срок оценки: at 2 years]
• Cumulative risk of leukemia relapse [Срок оценки: at 2 years]
• Cumulative risk of non-relapse mortality [Срок оценки: at 100 days and 2 years]
• Overall survival [Срок оценки: at 3 years]
• Event-free survival [Срок оценки: at 3 years]
• GVHD- and relapse-free survival [Срок оценки: at 3 years]

Критерии участия

Критерии включения

• 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%
• Life expectancy of at least 8 weeks
• Heart function: ejection fraction of at least 40%
• Consent to continue follow-up for 3 years

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Россия · 1 центр

• National medical research center of pediatric haematology, oncology and immulogy named aft — Moscow

Идентификаторы

NCT: NCT07366801 · NCHPOI- 2025-14

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗