Neonatal Thymus Transplantation in Humans

Study Overview
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Brief Summary
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The goal of this clinical trial is to demonstrate the safety of the neonatal thymus transplant in an adult patient. The main questions it aims to answer are: Is the neonatal thymus transplant a safe procedure? What is the adverse event profile of the neonatal thymus transplant? This is a single-subject study; thus, there will not be comparison groups. The participant will receive multidisciplinary supportive care before, during, and after the procedure.

Detailed Description
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Inadequate thymopoiesis is probably related to autoimmunity, immunodeficiency, and immunosenescence. Enhancing thymopoiesis may be attractive for managing or studying such immunologic phenomena. Thymopoiesis is supported by the adult thymus transplant, as demonstrated in different animal models. Several approaches to enhance thymopoiesis in humans have been reported, which include in-vitro and in-vivo regeneration of the thymus and avascular grafting of allogeneic processed thymic tissue, among others. Although a supermicrosurgical technique for neonatal thymus transplantation was recently described in rabbits, it has never been described in humans. This technique can be used to perform a neonatal thymus transplantation in humans. If this technique demonstrates to be safe, future studies will follow to investigate its effect on thymopoiesis and its efficacy on different health conditions. This single-subject, first-in-humans clinical trial aims to demonstrate the safety and investigate the adverse effect profile of the neonatal thymus transplant in an adult with acute myeloid leukemia who is not candidate for bone marrow transplant, nor intensive chemotherapy. This human model not only allows to study the safety of the neonatal thymus transplant, it will also allow to investigate the effect of the procedure on thymopoiesis.

Official Title
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A First-in-Humans Supermicrosurgical Technique for the Neonatal Thymus Transplantation

Conditions
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Safety Issues

Intervention / Treatment
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* Procedure: Neonatal thymus transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute leukemia in palliative care, either myeloid (AML) or lymphocytic (ALL). Not candidate for bone marrow transplant. Not candidate for intensive chemotherapy. Exclusion Criteria: Past medical history of bone marrow transplant. Past medical history of severe cognitive decline or dementia. Past medical history of severe liver failure. Past medical history of chronic kidney disease (CKD) stage 4-5. Past medical history of acute coronary syndrome within the past 90 days. Past medical history of acute ischemic stroke within the past 90 days. Past medical history of decompensated congestive heart failure (CHF) within the past 90 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Single-subject study of a supermicrosurgical technique for neonatal thymus transplantation in an adult with acute myeloid leukemia who is not candidate for bone marrow transplant, nor intensive chemotherapy. The participant will receive multidisciplinary supportive care before, during and after the procedure. The safety and adverse event profile will be assessed throughout the study. The graft will be explanted 14-21 days after the procedure. Thymopoiesis will be measured at baseline and at postoperatve day 14-21, before explantation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neonatal thymus transplantation<br>Supermicrosurgical technique for neonatal thymus transplantation into the subject's radial forearm. The donor will be a neonate subject to corrective heart surgery via sternotomy requiring routinary partial thymectomy. | Procedure: Neonatal thymus transplantation<br>* The donor's neonatal thymus vessels will be dissected right after the routinary partial thymectomy. These vessels will be anastomosed into the recipient's penetrating vessels within the radial forearm by using a supermicrosurgical technique. The graft will be explanted at day 14-21 after the procedure.<br>* Other names: Multidisciplinary supportive care before, during and after the procedure.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) | Incidence of AEs and of clinically relevant changes in vital signs values, symptoms, physical examination findings, laboratory and imaging safety data. | 14-21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thymic graft functioning | Change in percentage (%) of naïve (CD45+ CD3+ CDRA+) and memory (CD45+ CD3+ CDRA-) T lymphocytes over the total number of T lymphocytes by flow cytometry before engrafting (day -1), and before explant (day +14-21), as biomarkers of thymopoiesis. | 14-21 days | 
| Tissue viability | Presence and extent (if any) of the graft rejection by light microscopy with eosin-hematoxylin and immunochemistry staining in the explanted thymic tissue at post-operative day 14-21. | 14-21 days | 
| Donor-receptor compatibility | Human Leukocyte Antigens (HLA) typing. | 14-21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-in-humans, Clinical trial, Safety, Supermicrosurgery, Neonatal thymus transplant