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
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Cyclosporine A (CsA), Sirolimus, Ruxolitinib (JAKAVI®), Abatacept.
- Who it may be relevant to
- Registry conditions: Acute Myeloid Leukemia, Relapsed, Acute Lymphoblastic Leukemia, High Risk, Acute Myeloid Leukemia, High Risk, Acute Lymphoblastic Leukemia, Relapse. Basic parameters: 1 year — 25 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Russia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
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
Overview
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
Interventions
- 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 pharmacolog - 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 pharmacolog - 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,
Primary outcome measures
- Feasibility- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Time frame: day 30]
- Safety- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Time frame: 120 days after HSCT]
Secondary outcome measures (10)
- Cumulative probability of engraftment [Time frame: up to 100 day]
- Time to engraftment of neutrophils and platelets [Time frame: 100 day after HSCT]
- Cumulative risk of acute GVHD Grade II-IV [Time frame: up to 100 days after HSCT]
- Cumulative risk of viral [Time frame: at 120 day after HSCT]
- cumulative risk of developing severe chronic GVHD [Time frame: at 2 years]
- Cumulative risk of leukemia relapse [Time frame: at 2 years]
- Cumulative risk of non-relapse mortality [Time frame: at 100 days and 2 years]
- Overall survival [Time frame: at 3 years]
- Event-free survival [Time frame: at 3 years]
- GVHD- and relapse-free survival [Time frame: at 3 years]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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%
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Sequential
- Masking
- Single blind
- Primary purpose
- Treatment
Study locations
Russia · 1 center
- National medical research center of pediatric haematology, oncology and immulogy named aft — Moscow
Identifiers
NCT: NCT07366801 · NCHPOI- 2025-14