Mesenchymal Stromal Cell Therapy in Renal Recipients

NCT02057965 | Unknown Phase 2 DMC

• 2 other identifiers: NL43712.000.132013-000819-25
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the hypothesis that MSCs in combination with Everolimus facilitate Tacrolimus withdrawal, reduce fibrosis and decrease the incidence of opportunistic infections compared to standard tacrolimus dose.

Conditions

Renal Transplant Rejection; Fibrosis

Keywords

Mesenchymal Stromal Cells; Allograft rejection; Fibrosis

Outcome Measures

Primary Outcomes (1)

• Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups

  at 6 months compared to 4 weeks post transplant

Secondary Outcomes (6)

• Renal function and proteinuria

  6 months

• Number of participants with CMV and BK infection an other opportunistic infections between groups

  6 months

• Number of participants with adverse events

  6 months

• composite end point efficacy failure (biopsy proven acute rejection, graft loss or death)

  6 months

• Presence of donor specific antibodies and immunologic monitoring

  6 months

Study Arms (2)

Mesenchymal Stromal Cells + Everolimus

ACTIVE COMPARATOR

Intervention: two doses of autologous bone marrow (BM) derived Mesenchymal Stromal Cells IV, 7 days apart, 6 and 7 weeks after transplantation in combination with Certican® (1.5mg/day). Doses of MSCs will be 1-2x10\^6 million MSCs per/kg body weight. At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus wil be halved, after 2 weeks stopped)

Drug: Mesenchymal Stromal Cells

Everolimus + Tacrolimus

NO INTERVENTION

Patients in the control group will receive Certican® (1.5 mg b.i.d.) and standard dose tacrolimus (through levels 6-8 ng/ml after 6 weeks).

Interventions

Mesenchymal Stromal Cells DRUG

Two doses of autologous bone marrow (BM) derived MSCs IV, 7 days apart, 6 and 7 weeks after transplantation. Doses of MSCs will be 1-2x10\^6 million MSCs per/kg body weight

Also known as: Bone marrow derived mesenchymal stromal cells

Mesenchymal Stromal Cells + Everolimus

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 deceased, living-unrelated or non-HLA identical living related donor \> 50 years of age.
• Panel Reactive Antibodies (PRA) ≤ 10%.
• 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.

You may not qualify if:

• Double organ transplant recipient.
• Biopsy proven acute rejection (according to the Banff criteria) in the first 6 weeks after transplantation.
• 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.
• Patients who have had a previous BM transplant.
• 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.
• 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 TB, BK) after transplantation.
• Known recent substance abuse (drug or alcohol).
• Contraindications to undergo a BM biopsy.
• Patients who are recipients of ABO incompatible transplants.
• Cold ischemia time \>30 hrs.
• 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).

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Related Publications (3)

• Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE, Rabelink TJ. Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med. 2013 Feb;2(2):107-11. doi: 10.5966/sctm.2012-0114. Epub 2013 Jan 24.

  PMID: 23349326 RESULT

• Hendriks SH, Heidt S, Schulz AR, de Fijter JW, Reinders MEJ, Koning F, van Kooten C. Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients. Transpl Int. 2023 Jun 23;36:11329. doi: 10.3389/ti.2023.11329. eCollection 2023.

  PMID: 37426430 DERIVED

• Reinders ME, Bank JR, Dreyer GJ, Roelofs H, Heidt S, Roelen DL, Al Huurman V, Lindeman J, van Kooten C, Claas FH, Fibbe WE, Rabelink TJ, de Fijter JW. Autologous bone marrow derived mesenchymal stromal cell therapy in combination with everolimus to preserve renal structure and function in renal transplant recipients. J Transl Med. 2014 Dec 10;12:331. doi: 10.1186/s12967-014-0331-x.

  PMID: 25491391 DERIVED

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Marlies EJ Reinders, MD/PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD/PhD

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 7, 2014
• Study Start: March 1, 2014
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2022
• Last Updated: September 17, 2020

Record last verified: 2020-09

Locations

NL (1)