Year 8 (Supplement)
Since its inception in 2015, the UCSD CIRM Alpha Stem Cell Clinic (ASCC) has launched 30 trials (67% industry-sponsored), enrolled 275 patients, engaged a network of trial experts and accelerated patient accrual with ASCC network partners. Together, we have translated the $8.69 million CIRM ASCC grant and a $100 million T. Denny Sanford philanthropic gift to establish the Sanford Stem Cell Clinical Center (SSCCC) into $312.5 million in additional grants, philanthropy, and industry-sponsored clinical trials. The UCSD CIRM ASCC and the SSCCC teams have developed a unique design-to-delivery framework for clinical trial pipeline development in cancer, metabolic disease, and neurological disease.
Our successful track record of clinical trial initiation and completion has been predicated on risk mitigation strategies that are built into the project from the earliest stages of planning and implementation. These efforts have led to achievement of important ASCC milestones, including launching a CIRM-funded Phase 1/2 stem cell gene therapy clinical trial for patients with cystinosis; completion of a Phase 1 spinal cord injury study that showed improvements in motor function; and FDA approval for a Phase 3 registration trial of a UCSD CIRM team-developed and CIRM and Oncternal-sponsored ROR1-targeting monoclonal antibody, Cirmtuzumab (Zilovertamab) for chronic lymphocytic leukemia that will provide biomarkers for IND enabling studies with a related CAR-T cell product.
By leveraging UC San Diego Health’s location in a leading biotechnology hub, the UCSD CIRM
ASCC has been able to maximize access and work collaboratively to refine regenerative medicine clinical trial protocols that will enhance clinical outcomes. For example, with our ASCC trial experts in Neurosurgery and Anesthesiology, we have established a collaboration with a local company to develop a Phase 2 trial of an hESC-derived oligodendrocyte precursors trial for patients with spinal cord injury. Moreover, by partnering early in the development of a switchable CAR-T cell product with Calibr, a non-profit translational research institute at Scripps, we are conducting the first-in-human study for refractory lymphoid malignancies with a blood and marrow transplant trial expert. To expand patient access, we helped to recruit City of Hope.
The launch of the CIRM Alpha Stem Cell Clinic Network fostered the establishment of
a robust and vigorous California state-wide infrastructure for the acceleration of clinical trials in regenerative medicine. UC Davis & City of Hope ASCCs UCD and COH ASCCs are sites in a multi-center Phase 1b/2 trial that is testing a cirmtuzumab/ibrutinib combination therapy for patients with B-cell lymphoid malignancies with UCSD serving as the reliant site (Oncternal, NCT03088878). City of Hope ASCC UCSD ASCC served as a site for a COH-initiated Phase 1 multi-center trial testing AB-205, a cell therapy consisting of human engineered cord blood endothelial cells, in adults with Hodgkin or non-Hodgkin lymphoma following autologous stem cell transplantation (Angiocrine, NCT03925935; COH reliant site). Our site also supported recruitment for a COH clinical study testing the use of blood plasma as a potential treatment for COVID-19 (NCT04497779).
Our site collaborates with the UCLA ASCC in manufacturing for a Phase 1/2 study
to test a stem cell gene therapy for cystinosis (NCT03897361; UCSD ASCC). The UCLA GMP
facility oversees manufacturing of cells transfected with lentiviral vectors for this trial. In addition, UCSD supported UCLA in a compassionate use IND filing that cross-referenced IND# 117975, held by UCSD trial expert Thomas Kipps, for a study of cirmtuzumab in patients with relapsed or refractory chronic lymphocytic leukemia (NCT02222688). The close relationship between our ASCC sites facilitated the rapid transfer of all required documents for IRB approval at UCLA as well as delivery of the study drug cirmtuzumab.
UCSD ASCC, in addition to UCD ASCC, were sites in a multi-center Phase 2 study
initiated by UCI that tested autologous dendritic cells loaded with autologous tumor associated
antigens for treatment of newly diagnosed glioblastoma (AIVITA, NCT03400917; UCI reliant site). The CIRM ASCC Network has developed innovative tools that have overcome many barriers to patient access and accelerated trial initiation and completion. There is great potential to build and expand upon these robust, existing Network relationships in several areas including manufacturing, community engagement, data platforms, education and training, specialized clinical trial cores, and in platforms supporting capacity building and quality improvement. The commitment to continue to work together as a Network to work to better serve Californians has been memorialized in a group letter to CIRM. We firmly believe that preferential utilization of the ASCC network by study sponsors will result and that patients, sponsors and health care providers will benefit.