Allogeneic Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients

NCT ID: NCT02387151

Last Updated: 2019-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2018-11-30

Brief Summary

This study will test whether selected allogeneic bone marrow derived MSCs are safe by assessing the composite end point Biopsy Proven Acute Rejection (BPAR)/ graft loss at 12 months.

Detailed Description

Kidney transplantation has improved survival and quality of life for patients with end-stage renal disease. However, despite advances in immunosuppressive therapy, long-term allograft survival outcomes have not improved over the last decade.

A promising novel therapeutic immunosuppressive option in the treatment of renal recipients with a profound effect on the fibrosis reaction is the clinical application of mesenchymal stromal cells (MSCs). Allogeneic MSCs offer the advantage of availability for clinical use without the delay required for expansion.

Although it is believed that allo MSCs are immune privileged, they could possibly elicit an anti-donor immune response, which may increase the incidence of rejection/ graft loss and impact the allograft survival on the long term. These safety issues should be studied before further studies are planned with allogeneic MSCs in the transplant setting.

MSCs are infused at a time point when immune suppression is lowered and the kidney is at increased risk for developing immune mediated injury. In addition, a large amount of the kidneys already has signs of fibrosis at this time point and MSCs might reduce the fibrosis which so importantly affects long term survival. MSCs will have no Human Leucocyte Antigen (HLA) sharing with the mismatches of the donor and the recipient should have no antibodies directed to the MSCs to reduce the anti-donor immune respons risk.

Conditions

Rejection; Graft Loss

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mesenchymal stromal cells

allogeneic mesenchymal stromal cell infusion

Group Type: EXPERIMENTAL

mesenchymal stromal cells

Intervention Type: DRUG

2 doses of 1-2x10\^6 allogeneic bone marrow derives MSCs IV per/kg body weight at weeks 25 and 26 after transplantation

Interventions

mesenchymal stromal cells

2 doses of 1-2x10\^6 allogeneic bone marrow derives MSCs IV per/kg body weight at weeks 25 and 26 after transplantation

Intervention Type: DRUG

Other Intervention Names

MSC; bone marrow derived mesenchymal stromal cells

Eligibility Criteria

Inclusion Criteria

• Subject is willing to participate in the study, must be able to give informed consent and the consent must be obtained prior to any study procedure.
• Recipients of a first kidney graft from a living-unrelated or non-HLA identical living related donor.
• Panel Reactive Antibodies (PRA) ≤ 50%.
• Patients must be able to adhere to the study visit schedule and protocol requirements.
• If female and of child-bearing age, subject must be non-pregnant, non-breastfeeding, and use adequate contraception.

• Subjects who currently an active opportunistic infection at the time of MSC infusion (e.g., herpes zoster [shingles], cytomegalovirus (CMV), Pneumocystis carinii (PCP), aspergillosis, histoplasmosis, or mycobacteria other than tuberculosis, BK) after transplantation.
• Known recent substance abuse (drug or alcohol).
• Patients who are recipients of ABO incompatible transplants.
• Patients with severe total hypercholesterolemia (>7.5 mmol/L) or total hypertriglyceridemia (>5.6 mmol/L) (patients on lipid lowering treatment with controlled hyperlipidemia are acceptable).

Exclusion Criteria

• Double organ transplant recipient.
• Biopsy proven acute rejection (according to the Banff criteria) in the 4 weeks before MSC infusion.
• Patients with evidence of active infection or abscesses (with the exception of an uncomplicated urinary tract infection) before MSC infusion.
• Patients suffering from hepatic failure.
• Patients suffering from an active autoimmune disease.
• A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
• Use of any investigational drug after transplantation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

M.E. J. Reinders

MD/PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marlies EJ Reinders, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leiden University Medical Center

Leiden, , Netherlands

Countries

Netherlands

References

Reinders ME, Dreyer GJ, Bank JR, Roelofs H, Heidt S, Roelen DL, Zandvliet ML, Huurman VA, Fibbe WE, van Kooten C, Claas FH, Rabelink TJ, de Fijter JW. Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients: the neptune study. J Transl Med. 2015 Nov 4;13:344. doi: 10.1186/s12967-015-0700-0.

Reference Type: DERIVED

PMID: 26537851 (View on PubMed)

Other Identifiers

2013-005407-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL4724400013

Identifier Type: -

Identifier Source: org_study_id