scholarly journals Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aekkachai Tuekprakhon ◽  
Siripakorn Sangkitporn ◽  
Adisak Trinavarat ◽  
Aulia Rahmi Pawestri ◽  
Visit Vamvanij ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cell ◽  
Adverse Events ◽  
Retinitis Pigmentosa ◽  
Phase I ◽  
Intravitreal Injection ◽  
Phase I Clinical Trial ◽  
Long Term Follow Up

Abstract Background Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP. Methods This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences. Results During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3. Conclusion Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention. Trial registration ClinicalTrials.gov, NCT01531348. Registered on February 10, 2012

Survivin-responsive conditionally replicating adenovirus for patients with advanced sarcoma demonstrated potent and long-term efficacy and high safety in a phase I clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11512-11512
Author(s):  
Satoshi Nagano ◽  
Toshitaka Futagawa ◽  
Eriko Sumi ◽  
Nobuhiro Ijichi ◽  
Munekazu Yamaguchi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Phase I Clinical Trial ◽  
Oncolytic Viruses ◽  
High Dose ◽  
Liver Transaminase ◽  
Musculoskeletal Tumors ◽  
Choi Criteria

11512 Background: Whereas one of oncolytic viruses (OVs), inducing selective tumor killing and systemic anti-tumor immunity, was approved by FDA in 2015, the best OV that more safely and efficiently treats intractable cancers has not been successfully developed. By our platform technology to efficiently construct next-generation OVs, i.e., “conditionally replicating adenoviruses (CRAs) that target and/or treat tumor cells with multiple factors” (m-CRAs), we identified that among candidates, survivin-responsive m-CRAs (Surv.m-CRAs) exhibited the most potent antitumor efficacy and cancer selectivity ( i.e., safety) in preclinical studies ( Cancer Res, 2005 et al.). Here we present the data of First-In-Human phase I clinical trial of Surv.m-CRA-1 for musculoskeletal tumors (MST). Methods: This single-arm, open label study included 9 patients with unresectable and advanced MST. Patients underwent a single intratumoral injection of either 1×10^10 viral particle (vp) (low), 1×10^11 vp (mid) or 1×10^12 vp (high). The primary endpoints were safety and tolerability. The secondary endpoints included the local control of treated tumor at one month, defined by RECIST and Choi criteria, analysis of dissemination of Surv.m-CRA-1, serum cytokine and adenoviral antibody. Long-term follow-up was done in some patients. Results: Four patients (44.4%) had grade 3 or higher adverse events, including lymphopenia, leukocytopenia and mildly elevated liver transaminase in 2, 1 and 1 patient, respectively. Virus excretions, including second peak of viremia from viral replication in tumor, were observed in 1, 2 and 3 patients of low, mid and high dose, respectively. Out of 9 patients, 5 PR, 3 SD and 1 PD by Choi, and 8 SD and 1 PD by RECIST were observed. During follow-up, another 1 and 2 patients became PR by Choi and RECIST, respectively. Of note, long-term PR (over 2 years) after a single injection of Surv.m-CRA-1 was achieved in two chordoma cases in low dose. Conclusions: Surv.m-CRA-1 was well tolerated and showed antitumor activity for prolonged periods against advanced MST. We about to start Phase I/II study of multiple injections of Surv.m-CRA-1 for advanced solid tumors in two-arms for musculoskeletal tumors and pancreatic cancer. Clinical trial information: R000026464 .

scholarly journals Matrix-Delivered Autologous Mesenchymal Stem Cell Therapy for Refractory Rectovaginal Crohn’s Fistulas

2019 ◽  
Vol 26 (5) ◽  
pp. 670-677 ◽  
Author(s):  
Amy L Lightner ◽  
Eric J Dozois ◽  
Allan B Dietz ◽  
Joel G Fletcher ◽  
Jessica Friton ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Adverse Events ◽  
Phase I ◽  
Phase I Clinical Trial ◽  
Fistula Tract ◽  
Serious Adverse Events ◽  
Fistula Plug ◽  
Rectovaginal Fistulas

Abstract Background Crohn’s rectovaginal fistulizing disease remains notoriously difficult to treat. A phase I clinical trial to evaluate the safety and feasibility of a novel protocol using a mesenchymal stem cell (MSC)–coated Gore Bio-A fistula plug for the treatment of medically and surgically refractory Crohn’s rectovaginal fistulas was conducted. Methods Five patients underwent an autologous subcutaneous adipose tissue harvest via a 2-cm abdominal wall incision at time of exam under anesthesia (EUA) with seton placement. MSCs were isolated, expanded, and impregnated on the plug. After 6 weeks, patients returned to the operating room for placement of the MSC-coated plug. The primary end points were safety and feasibility; the secondary end point was clinical and radiographic healing at 6 months. Results Five female patients (median age [range], 49 [38–53] years) with a median disease duration (range) of 23 (7–34) years who were on biologic (n = 5) or combination therapy (n = 3) had successful harvest and expansion of MSCs and delivery of the Gore Bio-A plug. There were no serious adverse events or adverse events related to the MSCs or plug during the 6-month follow-up. At 6 months, 3 patients had complete cessation of drainage, and 2 had >50% reduction in drainage; all had a persistent fistula tract identified on magnetic resonance imaging and EUA at 6 months. Conclusions Surgical placement of an autologous adipose-derived MSC-coated fistula plug in diverted patients with Crohn’s rectovaginal fistulas was safe and feasible. All patients had a reduction in the size of their fistula tract, and 3 of 5 had cessation of drainage, but none achieved complete healing. This was a phase I clinical trial of autologous mesenchymal stem cells on a plug for rectovaginal Crohn’s fistulas.

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