We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Using T-Cell Alloreactivity and Chimerism to Guide Immunosuppression Minimization in Intestinal Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04804891
Recruitment Status : Recruiting
First Posted : March 18, 2021
Last Update Posted : March 17, 2023
Sponsor:
Collaborator:
Ossium Health, Inc.
Information provided by (Responsible Party):
Columbia University

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of this study is to investigate the safety and feasibility of giving intestinal transplant patients CD34+ stem cells (the cells that make all the types of blood cells) obtained from their organ donor's bone marrow. The goal of this is to develop a post-transplant treatment strategy that controls rejection while reducing the high risk of infection and malignant disease associated with the high levels of immunosuppression medication(s) that intestinal and multi-organ transplant patients must take. Infusion of bone marrow cells from the same donor of the transplanted organ(s) could promote a state called "mixed chimerism" in which both donor cells and recipient cells coexist in the body with the ultimate goal of minimizing the amount of immunosuppression medication(s) needed.

Condition or disease Intervention/treatment Phase
Intestinal Transplantation Biological: Cell Therapy Phase 1

Detailed Description:

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Using T-Cell Alloreactivity and Chimerism to Guide Immunosuppression Minimization in Intestinal Transplantation
Actual Study Start Date : October 22, 2021
Estimated Primary Completion Date : December 2028
Estimated Study Completion Date : December 2028
Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Graft survival rate [ Time Frame: Up to 1 month after transplantation ]
    Percentage of individuals with graft survival.

  2. Retention rate [ Time Frame: Up to 1 month after transplantation ]
    Percentage of individuals with retention from any cause.

  3. Graft survival rate [ Time Frame: Up to 1 year after transplantation ]
    Percentage of individuals with graft survival.

  4. Retention rate [ Time Frame: Up to 1 year after transplantation ]
    Percentage of individuals with retention from any cause.

  5. Graft survival rate [ Time Frame: Up to 3 years after transplantation ]
    Percentage of individuals with graft survival.

  6. Retention rate [ Time Frame: Up to 3 years after transplantation ]
    Percentage of individuals with retention from any cause.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients actively listed as candidates for intestinal or multi-visceral transplant at the study site; while all patients who are actively listed in United Network for Organ Sharing (UNOS) for intestinal and/or multi-visceral transplantation, including those who have previously received a multi-visceral transplant and are re-listed, are eligible for participation, the following are examples of listing criteria suitable for enrollment in this clinical trial:

    • Short Bowel Syndrome (SBS) due to:

      • Trauma (multiple resections/explorations and/or vascular abdominal trauma superior mesenteric artery (SMA) / superior mesenteric vein (SMV) injuries)
      • Gastroschisis
      • Volvulus
      • Necrotizing Enterocolitis
      • Intestinal Atresia
      • Crohn's Disease
      • Hirschprung's Disease
    • Chronic Intestinal Pseudo-Obstruction

    • Malabsorption:

      • Microvillus Inclusion Disease
      • Tufting Enteropathy
      • Complete portomesenteric thrombosis with cirrhosis

    • Slow-growing, low-malignancy potential tumors infiltrating mesenteric root:

      • Gardner's Syndrome
      • Familial Adenomatous Polyposis
      • Desmoid Tumor with Intra-Abdominal Infiltration
      • Endocrine Tumors
    • Re-transplant candidates who lost the first graft to rejection or patients who have higher risk of toxicity from chronic long term immunosuppression (i.e., patients with chronic kidney disease)
  • Patient commits to planned follow up at a study site for the 48-month duration of study procedures
  • Age ≥18 years old and ≤65 years old
  • Subjects or capable of signing the informed consent document themselves

Exclusion Criteria:

  • Active systemic infection with hemodynamic instability and/or sepsis
  • Patients with known immunodeficiency syndrome
  • Carcinoma with metastasis (except neuro-endocrine tumors, even in the presence of metastasis these patients may undergo multivisceral/cluster transplantation)
  • Severe cardiovascular and/or respiratory instability, as defined by requirement of pressors or ventilator
  • Severe cerebral edema, with radiologic findings of effaced sulci and/or herniation
  • Poorly controlled hypertension (systolic blood pressure > 170 on at least 2 occasions), diabetes mellitus (HbA1c > 8), or uncontrollable seizure disorders
  • Age > 65 years
  • Documented history of non-compliance with medical therapy and follow-up
  • Substance addiction in the last six months
  • Psychosocial Instability: absence of a consistent reliable social support system
  • Significant or active psychiatric disorder associated with the inability to cooperate or comply with medical therapy
  • In the judgement of the clinical team, severely limited functional status with poor rehabilitation potential
  • Multi-organ failure and preceding CD34+ infusion
  • Pre formed panel reactive antibodies (PRA) mean fluorescein intensity (MFI) > 5000 by Luminex
  • Patients who are pregnant or breast-feeding or intend to get pregnant during the study period
  • Patients who have developed moderate or severe rejection before post-transplant day 11
  • Vulnerable populations, such as incarcerated or institutionalized individuals
  • Subjects with clinical features suggestive of GVHD
  • Subjects who are hemodynamically unstable (i.e., requiring vasopressor support)
  • Female subjects of childbearing age and male patients who are not using and/or unwilling to use an effective method of birth control for the duration of the trial activities
  • History of previous hematopoietic progenitor cell (HPC) infusion or transplant of any kind. Note: Human leukocyte antigen (HLA) mismatch will not be one of the exclusion criteria
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Clinical Research Core 212-305-3839 tk2388@cumc.columbia.edu

Locations
Layout table for location information
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    tk2388@cumc.columbia.edu   
Sponsors and Collaborators
Columbia University
Ossium Health, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Tomoaki Kato, MD Columbia University
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT04804891    
Other Study ID Numbers: AAAS8908
First Posted: March 18, 2021    Key Record Dates
Last Update Posted: March 17, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Columbia University:
CD34+ stem cells
Chimerism
Bone marrow stells