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

NCT07366801 | Recruiting Phase 2

• 1 other identifier: NCHPOI- 2025-14
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

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

Keywords

Acute myeloid leukemia; Acute lymphoblastic leukemia; relapse; T regulatory; CD3 depletion; allogeneic HSCT

Outcome Measures

Primary Outcomes (2)

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

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

  day 30

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

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

  120 days after HSCT

Secondary Outcomes (10)

• Cumulative probability of engraftment

  up to 100 day

• Time to engraftment of neutrophils and platelets

  100 day after HSCT

• Cumulative risk of acute GVHD Grade II-IV

  up to 100 days after HSCT

• Cumulative risk of viral

  at 120 day after HSCT

• cumulative risk of developing severe chronic GVHD

  at 2 years

Study Arms (4)

Cyclosporine A

ACTIVE COMPARATOR

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

Drug: Cyclosporine A (CsA)

Sirolimus

ACTIVE COMPARATOR

Drug therapy (pharmacological prophylaxis of GVHD) 2) Sirolimus

Drug: Sirolimus

Ruxolitinib

ACTIVE COMPARATOR

Drug therapy (pharmacological prophylaxis of GVHD) Ruxolitinib

Drug: Ruxolitinib (JAKAVI®)

Abatacept

ACTIVE COMPARATOR

Drug therapy (pharmacological prophylaxis of GVHD) Abatacept

Drug: Abatacept

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).

Cyclosporine A

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

Sirolimus

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

Ruxolitinib

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

Abatacept

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

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

Moscow, Russia

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclosporine; Sirolimus; ruxolitinib; Abatacept

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Globulins

Central Study Contacts

Michael Maschan, Prof

CONTACT

+79166512145; mmaschan@yandex.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2026
• First Posted: January 26, 2026
• Study Start: September 3, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): February 3, 2028
• Last Updated: January 26, 2026

Record last verified: 2025-12

Locations

RU (1)