6 Participants Needed

Cell Therapy for Intestinal Transplant Recipients

CR
Overseen ByClinical Research Core
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Columbia University
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study aims to reduce the amount of immunosuppression medication needed, it's possible that changes to your medication regimen might be part of the trial.

What data supports the effectiveness of the treatment CD34+ stem cells, Hematopoietic Stem Cells, Bone Marrow-Derived Stem Cells for intestinal transplant recipients?

Research shows that hematopoietic stem cells (HSCs) in intestinal transplants can help promote immune tolerance, which is important for transplant success. Additionally, bone marrow-derived cells (BMDCs) can transform into intestinal cells and aid in repairing damaged tissue, potentially improving transplant outcomes.12345

Is cell therapy using CD34+ stem cells safe for humans?

Studies show that CD34+ stem cells, used in various treatments, are generally safe for humans, with patients typically tolerating the infusions well and achieving successful engraftment. However, higher doses may increase the risk of complications like fever and engraftment syndrome.678910

How is the CD34+ stem cell treatment different from other treatments for intestinal transplant recipients?

The CD34+ stem cell treatment is unique because it uses specific stem cells from the bone marrow that have the ability to support blood cell production and potentially reduce immune reactions, which may help in better engraftment and tolerance in transplant recipients compared to other treatments.1112131415

Research Team

TK

Tomoaki Kato, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults aged 18-65 who need an intestinal transplant and can follow up for 48 months. It's open to those listed in UNOS, with conditions like Short Bowel Syndrome or specific tumors, but not for those with multi-organ failure, severe infections, or unstable health conditions. Pregnant women and individuals unable to use birth control are excluded.

Inclusion Criteria

I have Short Bowel Syndrome from surgery, injury, or a specific condition.
I can attend all study visits for the next 4 years.
All patients actively listed as candidates for intestinal or multi-visceral transplant at the study site
See 5 more

Exclusion Criteria

My cancer has spread, but it's not a neuro-endocrine tumor.
I have multiple organ failure and have received a CD34+ cell infusion.
I am older than 65.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Initial Treatment

Participants undergo intestinal transplantation and receive an infusion of donor CD34+ stem cells between post-operative day 11 to day 13

2 weeks
In-patient stay for transplantation and initial recovery

Follow-up

Participants are monitored for safety, effectiveness, and occurrence of GVHD after transplantation

Up to 4 years
Regular follow-up visits

Long-term Monitoring

Participants are monitored for retention and graft survival

Up to 3 years

Treatment Details

Interventions

  • CD34+ stem cells
Trial OverviewThe study tests the safety of using donor bone marrow cells (CD34+ stem cells) after an intestinal transplant to reduce rejection and lower immunosuppressant needs. The aim is achieving 'mixed chimerism,' where both recipient's and donor's cells coexist harmoniously.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Cell TherapyExperimental Treatment1 Intervention
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.
Group II: ControlActive Control1 Intervention
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.

CD34+ stem cells is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Hematopoietic Stem Cells for:
  • Autologous use in hematopoietic stem cell transplantation for certain conditions such as leukemia and lymphoma
  • Investigational use in intestinal transplantation for minimizing immunosuppression
🇪🇺
Approved in European Union as Hematopoietic Stem Cells for:
  • Autologous use in hematopoietic stem cell transplantation for certain conditions such as leukemia and lymphoma
  • Investigational use in various clinical trials including intestinal transplantation

Find a Clinic Near You

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials
1,529
Recruited
2,832,000+

Ossium Health, Inc.

Industry Sponsor

Trials
11
Recruited
200+

Findings from Research

In a study of 21 patients over 5 years, it was found that intestinal transplants can lead to long-term mixed chimerism, where both donor and recipient blood cells coexist, indicating a potential for immune tolerance.
Donor-derived hematopoietic stem and progenitor cells (HSPCs) were identified in various tissues, including the intestines and liver, suggesting that these cells may play a role in promoting tolerance and immune acceptance in transplant recipients.
Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool.Fu, J., Zuber, J., Martinez, M., et al.[2022]
Intestinal transplantation is the best treatment for patients with short bowel syndrome, and the study evaluated the effects of infusing autologous bone marrow mesenchymal stromal cells (BMSCs) in patients undergoing this procedure.
The results indicated a potential increase in epithelial chimerism with BMSC infusion, which could lead to better graft survival and reduced need for immunosuppressants, although further studies are needed to confirm these findings over time.
Evaluation of epithelial chimerism after bone marrow mesenchymal stromal cell infusion in intestinal transplant patients.Kilinc, S., Gurkan, UA., Guven, S., et al.[2018]
Bone marrow-derived cells (BMDCs) can successfully differentiate into intestinal epithelial cells long-term in chimeric mice, demonstrating their potential role in intestinal regeneration without special treatment.
In a study involving 40 irradiated C57BL/6 mice, 93.3% survival was observed one week post-transplantation, and BMDCs were found to express epithelial markers, indicating their successful engraftment and differentiation into various intestinal cell types.
Long-term repopulation effects of donor BMDCs on intestinal epithelium.Liu, D., Wang, F., Zou, Z., et al.[2021]

References

Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool. [2022]
Evaluation of epithelial chimerism after bone marrow mesenchymal stromal cell infusion in intestinal transplant patients. [2018]
Long-term repopulation effects of donor BMDCs on intestinal epithelium. [2021]
Stem cells as potential novel therapeutic strategy for inflammatory bowel disease. [2016]
Engraftment of mucosal stem cells into murine jejunum is dependent on optimal dose of cells. [2019]
What is the optimum number of CD34+ peripheral blood stem cells for an autologous transplant? [2005]
Association of CD34+ Cell Dose with Progression-free Survival after Allogeneic Peripheral Blood Hematopoietic Cell Transplantation in Children with Hematologic Malignancies. [2023]
Effect of CD34+ peripheral blood progenitor cell dose on hematopoietic recovery. [2019]
Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Clinical use of selected and expanded peripheral blood CD34+ cells: a preliminary report of feasibility and safety. [2004]
Allogeneic transplantation of positively selected peripheral blood CD34+ progenitor cells from matched related donors. [2015]
Who is hematopoietic stem cell: CD34+ or CD34-? [2015]
13.United Statespubmed.ncbi.nlm.nih.gov
Alloantigen presenting function of normal human CD34+ hematopoietic cells. [2021]
Absence of a CD34- hematopoietic precursor population in recipients of CD34+ stem cell transplantation. [2006]
15.United Statespubmed.ncbi.nlm.nih.gov
Hematopoietic recovery in cancer patients after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells. [2019]