Mesenchymal Stromal Cells in Living Donor Kidney Transplantation

NCT03478215 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Pro00012858U1111-1169-2289
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney transplantation is a good treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients receive induction therapy and immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. This research study will evaluate the safety and activity of mesenchymal stromal stem cells (MSCs) infusion compared to saline-only infusion in reducing the immune suppression necessary to achieve optimal renal function in renal transplant recipients. All participants will receive routine care: basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids.

Conditions

Renal Transplantation; Mesenchymal Stem Cells

Keywords

kidney transplantation; graft rejection

Outcome Measures

Primary Outcomes (1)

• Number of participants without any infusional toxicity, occurring within 24 hours of infusion.

  Infusional toxicity will be assessed as the occurrence of either 1) two or more participants having deep vein thrombosis (Grade 2 thrombotic event); 2) any participant having evidence of the first-pass phenomenon of cells trapping in the lung as evidenced by (a) shortness of breath at rest, (b) requiring ventilator support, or (c) pulmonary edema with hypoxia requiring support; or 3) Grade 4 hypertension or hypotension; or 4) acute myocardial infarction; or 5) new onset congestive heart failure; or 6) capillary leak syndrome; or 7) acute kidney injury; or 8) biopsy-proven rejection.

  24 hours from end of infusion

Secondary Outcomes (1)

• Number of participants without any acute rejection, graft loss, or death at 6 months post transplant.

  6 months post transplant

Study Arms (2)

Mesenchymal Stromal Stem Cells Infusion

EXPERIMENTAL

Intervention: Mesenchymal stromal stem cells infusion. This is the active investigational intervention, administered intravenously at surgery and day 4 post-transplant in a dose-escalation fashion beginning as 1x10\^6 cells for the first dose group, 2x10\^6 cells for the second dose group, or 3x10\^6 cells for the last dose group. The infusion set-up will be covered to mask the group assignment. Participants will also receive BASILIXIMAB (Simulect, for all subjects at a standard dose, 20mg reconstituted with normal saline or 5% dextrose) on the day of surgery and day 3 or 4 post-transplant administered by a member of the anesthesia team; TACROLIMUS (Prograf for maintenance therapy), MYCOPHENOLATE MOFETIL (Cellcept for maintenance therapy), and CORTICOSTEROIDS as routine care.

Biological: Mesenchymal Stromal Stem Cells (MSCs) Infusion

Placebo Infusion

PLACEBO COMPARATOR

Placebo: A normal saline infusion. This is the placebo intervention to occur at surgery and day 4 post-transplant. The infusion set-up will be covered to mask the group assignment. Participants will also receive BASILIXIMAB (Simulect, for all subjects at a standard dose, 20mg reconstituted with normal saline or 5% dextrose) on the day of surgery and day 3 or 4 post-transplant administered by a member of the anesthesia team; TACROLIMUS (Prograf for maintenance therapy), MYCOPHENOLATE MOFETIL (Cellcept for maintenance therapy), and CORTICOSTEROIDS as routine care.

Other: Normal Saline (Placebo) Infusion

Interventions

Mesenchymal Stromal Stem Cells (MSCs) Infusion BIOLOGICAL

Investigational infusion bag containing autologous mesenchymal stromal cells wrapped to cover contents to maintain the blind. Mesenchymal Stromal Stem Cells Infusion.

Also known as: Investigational autologous biological product

Mesenchymal Stromal Stem Cells Infusion

Normal Saline (Placebo) Infusion OTHER

Matching infusion containing normal saline wrapped to cover contents to maintain the blind. Normal Saline (Placebo) Infusion.

Also known as: Matching placebo infusion bag

Placebo Infusion

Eligibility Criteria

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

You may qualify if:

• Males and females from 18 to 65 years of age
• Planned to receive a primary kidney transplant from a living donor
• Low immunologic risk defined as
• No history of current or historical antidonor human leukocyte antigen (HLA) antibodies (DSA)
• Panel of Reactive Antibodies (PRA) \<20%, historical
• Low risk for thrombotic events and normal prothrombin time, international normalized ratio (INR) and partial thromboplastin time
• Women of child bearing potential have a negative serum pregnancy test prior to transplantation
• Women of child bearing potential (including perimenopausal women who have had a menstrual period within the previous 1 year) who agree to use 2 forms of effective birth control regimen (at least one of which is a barrier method) throughout the study period and for 6 weeks following the end of the study or the last dose of mycophenolate mofetil, whichever comes first.
• In the opinion of the investigator, the subject is capable of understanding and complying with the protocol.
• Subjects must have signed the informed consent document prior to performance of any study related procedure including screening procedure.

You may not qualify if:

• Recipient of multiple organ transplantation or scheduled for multiple organ transplantation
• Recipient with a donor-specific anti-HLA antibody or positive cross-match requiring deviation from standard immunosuppressive therapy
• Hepatitis C antibody positive, Hepatitis B antigen positive, or Hepatitis B core antibody positive
• Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrollment into this study
• Concurrent sepsis or active bacterial infection
• In the opinion of the investigator is anatomically a high-risk renal transplant with higher chance for thrombosis or bleeding
• Have an active malignancy or history of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been treated
• Women of child bearing potential who are breastfeeding
• History of HIV infection
• Subject is unwilling or unable to comply with the protocol or to cooperate fully with the Investigator or the site personnel.
• Subject is not deemed medically stable for the study in the opinion of the Investigator or the subject's nephrologist.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Houston Methodist Hospital System

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ahmed O Gaber, MD

  Houston Methodist Physicians Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: March 27, 2018
• Study Start: December 1, 2016
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)