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

Heart Transplantation Clinical Trial

— THYTECH  

Official title:

Randomized, Exploratory and Prospective Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of the Transfusion of Autologous Treg Cells Obtained From Thymic Tissue in the Prevention of Rejection in Heart Transplant Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04924491
• Other study ID #: THYTECH1-2018-005
• Secondary ID: 2018-003574-28
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 10, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: September 2023
• Source: Hospital General Universitario Gregorio Marañon
• Contact: Rafael Correa-Rocha, PhD
• Phone: +34 915866455
• Email: rafael.correa[@]iisgm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 11
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Transplantation

Intervention

Biological:
• Autologous thyTreg
Treg lymphocytic cells, differentiated, autologous, of thymic tissue, expanded and stimulated with Interleukin (IL-) 2 (thyTreg)

Locations

Country	Name	City	State
Spain	Hospital General Universitario Gregorio Marañon	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
Rafael Correa-Rocha	Fundación Familia Alonso, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of episodes of acute myocardial rejection (diagnosed by echocardiography) that require treatment in the 2 years post-transplant		24 months
Secondary	Number of Treg cells in peripheral blood		24 months
Secondary	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
Secondary	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
Secondary	Overall patient survival rate at 24 months.		24 months
Secondary	Change on parameters of electrocardiogram (PR, QRS and corrected QT interval) of transplanted heart.		24 months
Secondary	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
Secondary	Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03 criteria.		24 months