Clinical trial NCT04924491: Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Prevent Rejection in Heart Transplant Children
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Heart Transplantation
Keywords: Cardiac Disease
Regulatory T cell
Immunomodulation
Tolerogenic protocol
Immunosuppressive Agents
Immunologic Factors
Lead sponsor: Hospital General Universitario Gregorio Marañon
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2021-06-14
Enrollment: 11
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 24 months
Secondary outcomes:
measure: Incidence of episodes of acute myocardial rejection (diagnosed by echocardiography) that require treatment in the 2 years post-transplant
timeFrame: 24 months
measure: Number of Treg cells in peripheral blood
timeFrame: 24 months
measure: 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).
timeFrame: 24 months
measure: 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.
timeFrame: 24 months
measure: Overall patient survival rate at 24 months.
timeFrame: 24 months
measure: Change on parameters of electrocardiogram (PR, QRS and corrected QT interval) of transplanted heart.
timeFrame: 24 months
measure: Change on parameters of echocardiogram (mitral and tricuspid regurgitation; mitral and tissue mitral Doppler; and tricuspid and tissue tricuspid Doppler ) of transplanted heart.
timeFrame: 24 months
measure: Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03 criteria.
timeFrame: 24 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
Study officials:
affiliation: Hospital General Universitario Gregorio Marañon
name: Rafael Correa-Rocha, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bernaldo-de-Quiros E, Cozar B, Lopez-Esteban R, Clemente M, Gil-Jaurena JM, Pardo C, Pita A, Perez-Caballero R, Camino M, Gil N, Fernandez-Santos ME, Suarez S, Pion M, Martinez-Bonet M, Correa-Rocha R. A Novel GMP Protocol to Produce High-Quality Treg Cells From the Pediatric Thymic Tissue to Be Employed as Cellular Therapy. Front Immunol. 2022 May 16;13:893576. doi: 10.3389/fimmu.2022.893576. eCollection 2022.