A phase i study to evaluate the safety of wharton's jelly mesenchymal stem cells for the treatment of de novo high risk or steroid refractory acute Graft Versus Host Disease (aGVHD)

Abstract

Background & Aim Allogeneic hematopoietic stem cell transplantation used to manage hematologic malignancies, is frequently complicated by graft versus host disease (GvHD) leading to poor outcomes with increased non-relapse morbidity and mortality. Traditional immunosuppressive therapy has many side effects, thus, necessitating alternative therapies to treat GvHD. Based on their immunomodulation and immunosuppression properties, mesenchymal stem cells (MSCs) are being explored to treat acute GvHD. Currently, there are no cellular products approved in the United States to treat steroid refractory aGvHD. MSCTC-0010, manufactured at the Midwest Stem Cell Therapy Center's GMP facility, is an investigational product consisting of tissue-derived allogeneic, Wharton's Jelly MSCs. We investigated MSCTC-0010 for the treatment of de novo high-risk acute or steroid refractory GvHD in a Phase I, safety clinical trial (IND#17672). The MSCTC-0010 is manufactured by explantation, ex-vivo culture and expansion, and cryopreservation and is tested for identity, potency, sterility, and stability. Methods, Results & Conclusion Method MSCTC-0010 was delivered intravenously twice at a dose of 2 × 106cells/kg in the first cohort and 10 × 106cells/kg in the second cohort on day 0 and 7. GvHD was graded by organ (skin, liver, and gastrointestinal) involvement. The primary endpoint was to evaluate the safety of MSCTC-0010 in patients who experienced a treatment related adverse event. The secondary endpoints include achievement of complete response of aGvHD by day 42 and improvement of GvHD in 1 or more organs involved. Samples were drawn at regular intervals to explore biomarkers that correlate with biological response. Results The study enrolled 10 patients (ages 18-75). Safety of the MSCTC-0010 was demonstrated as there was no infusion related toxicity and no increased incidence of infections. The study showed aGvHD response in 7 of the 10 patients at day 28 (refer to table). A biomarker panel consisting of Reg 3-α and ST-2 was analyzed. Analysis of these two biomarkers showed a reduction from day 0 to day 42. Subjects who received the higher dose of MSCTC-0010 had a statistically significant decline in the Reg-3 α levels on day 7, 14, 21, and 28. The drop in levels correlated with the clinical response. ST-2 levels showed a significant decrease on day 28 and 42. Conclusion This Phase 1 trial with MSCTC-0010 successfully met its primary endpoint of safety. Treatment with MSCTC-0010 shows promise in patients with high risk aGvHD.