Using T-Cell Alloreactivity and Chimerism to Guide Immunosuppression Minimization in Intestinal Transplantation
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|ClinicalTrials.gov Identifier: NCT04804891|
Recruitment Status : Recruiting
First Posted : March 18, 2021
Last Update Posted : August 9, 2021
|Condition or disease||Intervention/treatment||Phase|
|Intestinal Transplantation||Biological: Cell Therapy||Phase 1|
Abdominal trauma, congenital abnormalities and ischemic injury cause intestinal damage that prevents the digestion and absorption of fluids and nutrients essential for life. Intestinal transplantation is life-saving for patients with complications related to the administration of intravenous nutrients. Approximately 100-160 intestinal transplants (ITx) are performed in the US annually. However, patient survival rates are far from optimal, due to high rejection rates resulting from an immune attack of the recipient against the donor, termed host-vs-graft (HVG) reactivity The high levels of global immunosuppression used to prevent rejection come with a high risk of infections and malignant disease (i.e. lymphoma). Thus, there is an urgent need for a well-tolerated treatment strategy that controls rejection while reducing these risks. Immune tolerance, in which the immune system regards the donor as "self" so that long-term graft acceptance is achieved without life-long immunosuppression, would accomplish this goal . Infusion of bone marrow cells from the same donor of the solid organs could promote a state called "mixed chimerism" in which both donor cells and recipient cells coexist in the body. Mixed chimerism has been shown to induce tolerance to the transplanted organ in animal models and in patients receiving kidney transplants.
The investigators propose studies to promote tolerance induction in intestinal transplant recipients by administering donor bone marrow stem cells to promote lasting mixed chimerism. The investigators' proposal builds on their demonstration that mixed chimerism commonly occurs in intestinal transplant (ITx) recipients without bone marrow transplant, and that its presence correlates with reduced rejection rates. However, this mixed chimerism is not permanent. The investigators have discovered that there are bone marrow stem cells in the donor intestinal grafts and that some of these survive and enter the bone marrow of the recipient. This process is facilitated by a phenomenon called a "lymphohematopoietic graft-vs-host responses (LGVHR)", in which T lymphocytes from the ITx donor attack recipient blood-forming cells to make "space" for their own establishment in the bone marrow, but do not induce GVHD. The investigators have also obtained evidence that this immune response suppresses rejection of the graft.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Using T-Cell Alloreactivity and Chimerism to Guide Immunosuppression Minimization in Intestinal Transplantation|
|Estimated Study Start Date :||September 2021|
|Estimated Primary Completion Date :||December 2028|
|Estimated Study Completion Date :||December 2028|
Experimental: Cell Therapy
Patients will receive an infusion containing 1x106/kg CD34+ cells. No more than 104 CD34+ T cells per kg recipient weight will be included in the infusion. Cadaveric donor CD34 cell infusion will occur at any time between post-operative day 11 to day 13 following transplantation.
Biological: Cell Therapy
Infusion of containing 1x106/kg CD34+ cells from donor bone marrow selected using the CliniMACS® CD34 Reagent System.
No Intervention: Control
Patients who do not consent to receive donor CD34 cell infusion or whose donor family declines consent for research use of donor bone marrow will receive their usual standard of care.
- Total number of participants with moderate to severe GVHD [ Time Frame: Up to 4 years after transplantation ]Total number of participants with moderate to severe (at least Grade II) graft-versus-host disease (GVHD) will be monitored.
- Graft survival rate [ Time Frame: Up to 1 month after transplantation ]Percentage of individuals with graft survival.
- Retention rate [ Time Frame: Up to 1 month after transplantation ]Percentage of individuals with retention from any cause.
- Graft survival rate [ Time Frame: Up to 1 year after transplantation ]Percentage of individuals with graft survival.
- Retention rate [ Time Frame: Up to 1 year after transplantation ]Percentage of individuals with retention from any cause.
- Graft survival rate [ Time Frame: Up to 3 years after transplantation ]Percentage of individuals with graft survival.
- Retention rate [ Time Frame: Up to 3 years after transplantation ]Percentage of individuals with retention from any cause.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04804891
|Contact: Clinical Research Coreemail@example.com|
|United States, New York|
|Columbia University Irving Medical Center/NYP||Recruiting|
|New York, New York, United States, 10032|
|Contact: Clinical Research Core 212-305-3839 firstname.lastname@example.org|
|Principal Investigator:||Tomoaki Kato, MD||Columbia University|