NCT03158896

Evaluation of Umbilical Cord-Derived Wharton's Jelly Stem Cells for the Treatment of Acute Graft Versus Host Disease

A Phase I Study To Evaluate the Safety of Umbilical Cord - Derived, Ex-Vivo Cultured and Expanded Wharton's Jelly Mesenchymal Stem Cells for the Treatment of De Novo High Risk Acute or Steroid Refractory Acute Graft Versus Host Disease

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: University of Kansas Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates the safety and effectiveness of two different doses of umbilical cord derived, ex-vivo cultured and expanded Wharton's jelly mesenchymal stem cells (MSCTC-0010) in the treatment of acute Graft versus Host Disease (aGVHD). The first 5 participants enrolled in the study will receive a lower dose of MSCTC-0010. If none of the first 5 participants have treatment-related serious adverse events (TRSAEs) for 42 days, then the next 5 participants will receive a slightly higher dose of MSCTC-0010.

Detailed description

The curative potential of Allogeneic hematopoietic stem cell transplantation (allo-HCT), when applied as a therapy in the management of hematologic malignancies, specifically, derives from an immunologically driven, graft-versus-tumor effect mediated principally by donor T-cells, and is associated with a lesser risk for relapse when compared to high dose chemo-radio therapy and autologous HCT. Donor derived T-cells are also responsible for mediating the occurrence of GVHD, a common transplant-related complication, affecting a significant percentage of patients undergoing allo-HCT leading to the destruction of host tissues. The standard initial treatment for both acute and chronic GVHD is steroid-based therapy. Unfortunately, many of these patients will become resistant to steroid therapy and will subsequently be treated with second-line immunosuppressive agents. De novo high-risk aGVHD and steroid-refractory aGVHD portends a very poor prognosis; second-line agents frequently prove ineffective, and as a result, survival is \< 10% at 5 years. Therefore, alternative therapies are needed to treat aGVHD following allo-HCT, particularly in the setting of de novo high-risk acute or steroid-resistant disease. Due to the large numbers of Mesenchymal stem cells (MSC) that can be obtained from the umbilical cord, the availability of this tissue, their higher growth rates and expansion capacity, and their immune properties, including: (1) low immunogenicity and lack of stimulation of allogeneic T-lymphocyte proliferation, (2) suppression of the proliferation of activated T-lymphocytes, (3) increased production of regulatory T-cells, and (4) a shift in the immune response towards tolerance, Wharton's jelly mesenchymal stem cells (WJMSC) may be a preferred option for MSC. The rationale for cell dosing in this protocol is based on published data from Kebriaei, et al. Dosing at 2 × 10\^6 MSC/kg body weight produced a complete response in 87.5% of the treated patients. Dosing at a level 4 times higher (8 × 10\^6 MSC/kg body weight) produced no improvement in complete response results. However, the higher dose produced some partial response and no patient failed to respond to therapy. Therefore, the Phase I study for MSCTC-0010 is designed to increase the dose of WJMSC from 2 × 10\^6 MSC to 10 × 10\^6 MSC/kg body weight, assuming no dose-limiting toxicity (DLT) is observed at the lower dose.

Conditions

• Acute Graft Versus Host Disease

Interventions

Type	Name	Description
BIOLOGICAL	MSCTC-0010 Dose Escalation	Cohort 1: 2.0 × 106 cells per kilogram (cells/kg) body weight, given on day 0 and on day 7 in Participants having de novo High Risk Acute or Steroid Refractory Acute Graft Versus Host Disease (HR/SR aGvHD) Cohort 2: 10 × 106 cells/kg of body weight, given on day 0 and on day 7 in Participants having de novo HR/SR aGvHD

Timeline

• Start date: 2018-07-09
• Primary completion: 2025-12-08
• Completion: 2025-12-08
• First posted: 2017-05-18
• Last updated: 2026-02-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study