Phase I Trial on the Safety of Delayed Infusion of a Naïve T Cell-Depleted Hematopoietic Graft With Memory T Cells in Solid Organ Transplant Recipients

NCT06997471 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: DUALGRAFT
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate the safety and feasibility of inducing hematopoietic mixed chimerism to promote immune tolerance and potentially reduce the need for lifelong immunosuppression in pediatric and adult patients undergoing solid organ transplantation (SOT), including kidney, lung, and multivisceral transplants. The main questions it aims to answer are:

• Is it safe to infuse a naïve T cell-depleted hematopoietic graft along with memory T-lymphocytes after SOT?
• Can this approach support immune tolerance and reduce the incidence of rejection and infection without long-term immunosuppression? Participants will:
• Undergo a solid organ transplant from a living or deceased donor.
• Wait through a stabilization period to ensure resolution of early transplant-related complications.
• Receive low-dose preconditioning (TLI and thymic irradiation) to prepare for hematopoietic stem cell transplantation.
• Be infused with a graft containing CD34+ progenitor cells, memory T cells (CD45RO+), and no naïve T cells (CD45RA+); in some cases, NK cells may also be included.
• Be followed for graft survival, immune tolerance, infection rates, and adverse events through regular clinical and immune monitoring visits.

Conditions

Solid Organ Transplant Complications; Solid Organ Transplant Recipients; Solid Organ Transplant Rejection

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events related to the investigational intervention.

  Safety and tolerability will be evaluated based on the incidence, nature and and severity of adverse events during study period. (clinical and laboratory).

  From enrollment to end of follow-up at 2 years after cell therapy administration

Secondary Outcomes (14)

• Feasibility of cell collection, processing and administration.

  From enrollment to 3 months after solid organ transplantation

• Mixed hematopoietic chimerism measurement.

  From therapy administration to 30 days and 100 days after investigational therapy administration

• Donor-Specific T Cell Clone Depletion

  One year post haematopoietic stem cell therapy and thereafter.

• Organ Rejection Rate

  From investigational therapy administration to 1 year after

• Graft Survival and Failure Rates

  From enrollment to end of follow-up at 2 years after cell therapy administration

Study Arms (1)

HSCT using a graft enriched in CD34+ hematopoietic progenitor cells

EXPERIMENTAL

The study intervention involves a HSCT using a graft enriched in CD34+ hematopoietic progenitor cells. This graft will be specifically engineered through depletion of naïve T-lymphocytes (CD45RA+) and patients will be supplemented with memory lymphocytes to support immune reconstitution and promote tolerance. The source of the hematopoietic stem cells (HSCs) will vary depending on whether the donor is a living related donor (HLA-identical or haploidentical) or a deceased donor. Graft Composition and Cell Doses * CD34+ cells: \< 1 x 107/kg will be intravenously infused as the primary source of hematopoietic progenitors. * Memory T-lymphocytes (CD45RO+): \< 3 x 107/kg will be administered. Naïve T-lymphocytes (CD45RA+) remaining in the memory fraction will always be \<1 x 104/kg, to minimize the risk of GVHD while supporting immune surveillance. * Only in haploidentical participants: NK cells (CD56+): \< 5 x 107/kg to promote graft tolerance and target residual malignant cells.

Biological: Investigational cellular therapy consisting on a HSCT using a graft enriched in CD34+, depleted of naïve T-lymphocytes and supplemented with memory lymphocytes

Interventions

Investigational cellular therapy consisting on a HSCT using a graft enriched in CD34+, depleted of naïve T-lymphocytes and supplemented with memory lymphocytes BIOLOGICAL

Infusion Schedule 1. Primary Infusion: the enriched graft, containing the CD34+ progenitors and depleted naïve T cells, will be infused after the patient has undergone conditioning therapy. 2. In the case of haploidentical donors, an additional NK cell infusion will be administered whenever possible around day 7 post-transplant from a non-mobilized apheresis collection, aiming to enhance graft tolerance and prevente HHV6 disease. 3. Post-Transplant Memory T cell Infusions: beginning on days 15 and 30, and then administered monthly up to a maximum of one year or until the supply is depleted, memory T cells will be infused. Conditioning Regimen Prior to HSCT, all patients will undergo a low-intensity conditioning regimen designed to allow engraftment of the donor cells while minimizing toxicity: 1. Total Lymphoid Irradiation (TLI): 8 Gy of total lymphoid irradiation will be administered. 2. Fludarabine: a total dose of 120 mg/m², spread over 4 days (-6 to -3 before transplant), will serv

HSCT using a graft enriched in CD34+ hematopoietic progenitor cells

Eligibility Criteria

• Age: 0 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pediatric patients (\<18 years old) who are candidates to receive intestinal or lung transplantation (before SOT).
• Pediatric (\<18 years old) or adult patients (≥18 years old) who are either candidates for renal transplantation or have already undergone renal transplantation and remain candidates for subsequent HSCT.
• Patients who provide informed consent (or their legal guardians in the case of minors) before any study-related procedures.
• Recipients should have no active infectious disease or other medical condition that would contraindicate the combined transplantation procedure, as determined by the investigational team.

You may not qualify if:

• Recipients with existing bone marrow disorders or those receiving medications known to adversely affect bone marrow function.
• Patients with advanced organ dysfunction (hepatic, cardiac, or pulmonary) incompatible with successful combined transplantation.
• Patients with active or uncontrolled autoimmune conditions that may interfere with transplantation and the induction of chimerism.
• Patients with known allergies to medications or products required for conditioning or transplantation.
• Patients with severe psychiatric or cognitive disorders that may interfere with adherence to study instructions or postoperative care.
• Patients currently enrolled in another clinical trial that could interfere with the outcomes or safety of this study.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Any other condition that, in the opinion if the Investigator, may interfere with the efficacy and/or safety evaluation of the trial.

Sponsors & Collaborators

• Francisco Hernández Oliveros: lead

MeSH Terms

Interventions

Antigens, CD34

Intervention Hierarchy (Ancestors)

Antigens, CD; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Central Study Contacts

Francisco María Hernández Oliveros, MD, PhD

CONTACT

+34 91 207 17 40; fhernandezo@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician in the Department of Pediatric Surgery. Head of the Pediatric Transplant Section.

Model Details: This study is a single-center, open-label clinical trial. Its primary goal is to evaluate the safety of inducing hematopoietic mixed chimerism to promote immunological tolerance in SOT recipients. A total of 10 participants will be recruited, either prior to their scheduled SOT or having already undergone SOT (in case of renal transplant recipients with a living donor), depending on enrollment feasibility.

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 30, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 30, 2025

Record last verified: 2025-05