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NCT Number: NCT07366801

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

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).

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Key information

Conditions

Acute Myeloid Leukemia, Relapsed Acute Lymphoblastic Leukemia, High Risk Acute Lymphoblastic Leukemia, Relapse Acute Myeloid Leukemia, High Risk Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myeloid, Acute Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-Lymphoma Recurrence

Age range

1 year–25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

National medical research center of pediatric haematology, oncology and immulogy named after Dmytriy Rogachyov, Moscow, 117198

Moscow, Russia

Location status: Recruiting

Location contact

Lena Smirnova

CONTACT

[email protected]

+7(985)130-61-03

About this study

  • Infusion of ex-vivo T-depleted peripheral blood hematopoietic stem cells (CD3 depletion product)
  • Infusion of donor lymphocytes enriched with T regulatory lymphocytes (CD25 selective product)
  • Drug therapy (pharmacological prophylaxis of GVHD)
  • Cyclosporine A
  • Sirolimus o Ruxolitinib o Abatacept

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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%

Treatment and study plan

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

Primary outcomes

  1. Feasibility- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time frame: day 30

    proportion of patients who received an infusion of the planned dose of regulatory T lymphocytes (at least 80%)

  2. Safety- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time frame: 120 days after HSCT

    Cumulative risk of GVHD Grade III-IV (target < 5%)

Secondary outcomes

  1. Cumulative probability of engraftment

    Time frame: up to 100 day

  2. Time to engraftment of neutrophils and platelets

    Time frame: 100 day after HSCT

  3. Cumulative risk of acute GVHD Grade II-IV

    Time frame: up to 100 days after HSCT

  4. Cumulative risk of viral

    Time frame: at 120 day after HSCT

    (CMV, ADV, EBV, HHV-6) DNA detection in blood, peak viral DNA load and the duration of detectable viral DNA (each virus separately)

  5. cumulative risk of developing severe chronic GVHD

    Time frame: at 2 years

    Severity of chronic GVHD

  6. Cumulative risk of leukemia relapse

    Time frame: at 2 years

  7. Cumulative risk of non-relapse mortality

    Time frame: at 100 days and 2 years

  8. Overall survival

    Time frame: at 3 years

  9. Event-free survival

    Time frame: at 3 years

  10. GVHD- and relapse-free survival

    Time frame: at 3 years

Study contacts

Contact information is provided by the study sponsor or research team.

Michael Maschan, Prof

CONTACT

[email protected]

+79166512145

Sponsors and collaborators

Lead sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Other

Registry information

Official study 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

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jan 26, 2026
Registry last updated
Jan 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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