Year 6/NCE

The CIRM Alpha Stem Cell Clinic at UC San Diego has made several clinical trial advances in cancer, spinal cord injury, diabetes, inflammatory bowel disease and heart failure. The main goal has been to establish safety, tolerability and proof of efficacy and we have transitioned a number of these trials to the proof of efficacy phases. The UCSD Alpha Clinic portfolio currently consists of 18 open trials and 48 trial subjects have received or are receiving treatment on these active trials.

The services of the Alpha Clinic that include regulatory submission and clinical trial coordination, together with the patient care provide by the Cell and Regenerative Medicine service and the Sanford Stem Cell Clinical Center, are integral to providing San Diego patients with experimental therapies in the regenerative medicine space that are not available anywhere else in the region. Due to the infrastructure established by the Alpha Clinic grant and complimented by infrastructure provided by UCSD and Sanford Stem Cell Clinical Center, we had an advantage that contributed greatly to the decision to the NASA award of $5 million in shared funding that Sanford Center received along with Space Tango for the project ‘Development of an Orbital Laboratory to Advance Stem Cell Therapies and Regenerative Medicine’. The improved US News and World Report rankings of UCSD released in 2021 are evidence that our institution’s reputation for innovative and compassionate patient care is top notch. The return on investment from the CIRM Alpha Clinic grant is considerable. Highlighted here are some of our most notable trials and accomplishments.

Stem Cell Gene Therapy for Inherited Disorders
A Phase 1, first-in-human CIRM funded clinical trial was launched at UCSD with Alpha Clinic support based on research conducted by UCSD’s Stephanie Cherqui and Edward Ball, together with Donald Kohn at UCLA. This ex vivo transduced autologous human CD34+ hematopoietic stem cells for treatment of cystinosis culminated in an actively accruing clinical trial at UCSD with Alpha Clinic support.

As a result of marrying cancer center activities to stem cell research activities it is possible to address an unmet medical need in a logical and safe manner.
UCSD partnered with Oncternal Therapeutics Inc. and through the CIRM Alpha Stem Cell Clinic launched a CLIN2 grant-funded Phase 1b/2 trial of Cirmtuzumab combined with Ibrutinib focuses on assessing safety and efficacy in patients with refractory B cell malignancies. The phase 1 results of this trial showed that decreased chronic lymphocytic leukemia (CLL) burden and delayed time to next treatment coincided with reversal of the stemness index and reversion to more normal hematopoiesis RNA sequencing signatures. The Phase 2 trial for CLL and Mantle Cell Lymphoma (MCL) of Cirmtuzumab combined with ibrutinib ¬¬¬has expanded to include other Alpha Stem Cell Clinic sites and showed a 50% complete response rate with delayed time to progression. We launched and completed accrual for a Phase 1b/2a breast cancer study in combination with placlitaxel with Oncternal providing Cirmtuzumab and with co-funding from the Moores Cancer Center and more recently a state grant to treat underrepresented minority (URM) populations with evidence of delayed time to progression in some patients.
A first-in-human Phase 1 study of induced pluripotent stem cells (iPS) derived NK cells sponsored by FATE therapeutics has been completed for patients with advanced solid tumors. In addition, we expanded the Aivita sponsored dendritic cell vaccine trials for glioblastoma multiforme (GBM) to ovarian cancer at UC San Diego and via an IRB reliance agreement with UCI’s Alpha clinic. To support these complex trials, we established a dedicated cell and regenerative medicine service (CRM) to ensure that patients are carefully monitored for immune-based adverse events both as inpatients and as outpatients.

Neural Stem Cell Regeneration and Repair
We completed a Phase 1 trial to evaluate safety and tolerability of a neural stem cell product sponsored by Neuralstem for chronic thoracic spinal cord injury patients. Proof-of-concept studies to evaluate neural repair and regeneration, including quantitative DT imaging and EMG measurements of recovery of neuronal function, showed early evidence of spinal cord remyelination. This trial has also helped to hone the requisite clinical trial expertise for initiating other acute spinal cord injury trials at UC San Diego including the enhancement of endogenous repair with scaffold from In Vivo. We have added to the interventional neurological repair portfolio by initiating the Discgenics-sponsored trial of MSCs for single level disc herniation. The expertise developed in the area of along with the surgical training facility at UCSD have established us as a highly recognized center for cellular product surgical delivery.