Cell Therapy with Treg Cells Obtained from Thymic Tissue (thyTreg) to Prevent Rejection in Heart Transplant Children

Phase 1

Recruiting

• Conditions: Heart Transplantation
• Interventions: Biological: Autologous thyTreg

• Registration Number: NCT04924491
• Lead Sponsor: Rafael Correa-Rocha

Brief Summary

The investigators developed a protocol to isolate Treg cells from thymic tissue (thyTreg) discarded in pediatric cardiac surgeries. After completing the pre-clinical studies, the investigators have initiated a phase I/II clinical trial to test the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children.

Condition or disease: Heart Transplantation Intervention/treatment: Regulatory T Cell (Treg) Infusion

Detailed Description

Current transplant practice is far from guaranteeing the life expectancy of patients, particularly if the patients are children. THYTECH aims to revolutionize the field of clinical immunology developing a new approach to govern the regulatory skills of immune system, preventing graft rejection and opening a new frontier in the treatment of immune diseases.

Transfer of regulatory T cells (Treg) has acquired growing interest in the race to achieve indefinite transplant survival. Up to now, the use of Treg therapy to prevent solid graft rejection in humans has demonstrated that this therapy is safe, but the clinical efficacy is limited. The small Treg numbers that can be purified from peripheral blood along with the low survival and limited suppressive capacity of differentiated Tregs obtained from adults have probably compromised the efficacy of this therapy.

The investigators have developed an innovative approach to overcome current barriers and make Treg transfer a reality equipped to achieve indefinite graft survival. The major innovation of THYTECH is the employment of thymic tissue, the site of Treg generation, as a new source of Tregs to obtain massive amounts of thymus-derived Tregs (thyTreg) with very high purity (\>95% of CD 25+ Foxp3+ cells) and improved survival and suppressive capacities. The investigators are recruiting patients in a clinical trial transferring autologous Tregs in heart-transplanted children to prevent graft rejection.

Study Timeline

• Study Start: 2020-09-10
• Study First Submitted: 2021-04-30
• Study First Submitted QC: 2021-06-09
• Study First Posted: 2021-06-14
• Status Verified: 2024-10
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-02-03
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

1. Patient under two years of age, who meets all the necessary requirements to undergo a heart transplant.
2. Patients without contraindication to immunosuppressive drugs.
3. Parents and/or guardians must be willing and able to understand the purpose and risks of the study and must sign the informed consent document

Exclusion Criteria

1. Patients with DiGeorge Syndrome, since their thymic function is affected.
2. Human immunodeficiency virus positive serology
3. Epstein-Barr virus active infection
4. Patients hyperimmunized with cytotoxic anti-human leukocyte antigen antibodies
5. Patients with a history of previous malignancy
6. Patients who have participated in other intervention studies in the last month.
7. Patients who have received induction therapy with Basiliximab or Thymoglobulin.
8. Patients who have previously been thymectomized or transplanted.
9. Patients who have been diagnosed with severe autoimmune disease (celiac disease, autoimmune hypothyroidism, autoimmune diabetes)
10. Patients who will receive an asystole heart

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
20.000.000 thyTreg /kg	Autologous thyTreg	Autologous thyTreg 20.000.000
10.000.000 thyTreg /kg	Autologous thyTreg	Autologous thyTreg 10.000.000

Primary Outcome Measures

Name	Time	Method
Repopulation of Treg cells in the patient, determined as the increase of Treg values in peripheral blood with respect to pre-transplant values or in comparison with a control cohort of non-treated patients.	24 months

Secondary Outcome Measures

Name	Time	Method
Incidence of episodes of acute myocardial rejection (diagnosed by echocardiography) that require treatment in the 2 years post-transplant	24 months
Change in the number of naive and memory Treg cells, and the production/levels of interferon gamma and interleukins (IL-4, IL-17A and IL-10).	24 months
Number of Treg cells in peripheral blood	24 months
Change on parameters of electrocardiogram (PR, QRS and corrected QT interval) of transplanted heart.	24 months
Overall patient survival rate at 24 months.	24 months
Change on parameters of echocardiogram (mitral and tricuspid regurgitation; mitral and tissue mitral Doppler; and tricuspid and tissue tricuspid Doppler ) of transplanted heart.	24 months
Decrease of cell subsets related with rejection (CD8 T cells subsets, activated T cells, antibody-secreting B cells) during the post-transplant follow-up period.	24 months
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03 criteria.	24 months

Trial Locations

Locations (1)

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain