The Innovation-Alpha Clinic for Cellular Therapies (I-ACT) – A Program for the Development and Delivery of Innovative Cell-based Treatments and Cures for Life-threatening Diseases.
The CIRM Alpha Stem Cell Clinic (ASCC) was opened at City of Hope on March 1, 2015. The award is intended to enable researchers to pursue important work that aims to bring the potential of stem cell treatments to fruition. Two clinical trials were identified to launch this center, and in the first year, we have added 8 additional studies. The current and future clinical studies include:
• Transplants of blood stem cells that have been genetically modified to treat patients with either AIDS or with AIDS-related lymphoma
• Use of neural stem cells to deliver drugs directly to cancers hiding in the brain and elsewhere
• T cell immunotherapy trials to treat patients with cancer
• Correction of hemophilia B by genetic editing of liver stem cells
To accomplish this, the City of Hope developed a novel approach to evaluation of these new therapies. Instead of using the existing Clinical Research Unit here, a dedicated outpatient clinic was established in the City of Hope Day Hospital and staffed with clinic nurses. The reason for this is reflected in the two-fold nature of the CIRM network of Alpha Stem Cell Clinics’ goals: the first is to accelerate the development of new stem cells therapies and the second is the achievement of a fiscally sustainable clinical activity. As the largest stem cell transplantation center in California, the City of Hope plan takes advantage of our clinical nursing expertise of the Day Hospital and of the business expertise that makes this out-patient transplant center sustainable.
Thus, the COH Alpha Clinic is an experiment in itself, testing whether this hybrid research unit is the best approach to introduction of new treatments to the clinic. CIRM funding has made it possible to bring the clinical staff together with the research staff in this way to accelerate development of stem cell research.
Reporting Period:
Year 2
The CIRM Alpha Stem Cell Clinic (ASCC) was created at City of Hope in March 2015 with the goal of enabling researchers to bring stem cell treatments to fruition. The clinic currently supports 17 active clinical trials of stem cell-based therapies, including:
• Transplants of blood stem cells that have been genetically modified to treat patients with either AIDS or with AIDS-related lymphoma
• Use of neural stem cells to deliver drugs directly to cancers hiding in the brain
• T cell immunotherapy trials to treat patients with hematological or solid tumor cancers
• Correction of hemophilia B by genetic editing of liver stem cells
• Use of selected and expanded T cells to attack cancer stem cells and treat cancer
The City of Hope ASCC is implemented in a dedicated outpatient clinic in the City of Hope Day Hospital. In this setting, the novel research treatments are being done by clinical nurses rather than by research nurses working in a separate clinical research unit, as is normally done. This allows the new stem cell treatment to be evaluated in the actual site where, if successful, it will become standard treatment.
As the largest stem cell transplantation center in California, the City of Hope plan takes advantage of our clinical nursing expertise of the Day Hospital and of the business expertise that makes this out-patient transplant center sustainable. This has worked well, and the City of Hope ASCC team has grown significantly in the second year of funding, now includes study coordinators, regulatory staff, a patient care coordinator, and other personnel.
Thus, the COH Alpha Clinic is an experiment in itself, as it tests whether this hybrid research unit, in which a nurse must have research and clinical skills, is the best approach to introduction of new stem cell treatments to the clinic. CIRM funding has made it possible to bring clinical and research staff together, and in this way to accelerate development of stem cell research.
Reporting Period:
Year 3
The CIRM Alpha Stem Cell Clinic (ASCC) was created at City of Hope in March 2015 with the goal of enabling researchers to bring stem cell treatments to fruition. The clinic currently supports 27 active clinical trials of stem cell-based therapies, including:
• Transplants of blood stem cells that have been genetically modified to treat patients with either AIDS or with AIDS-related lymphoma
• Use of neural stem cells to deliver drugs directly to cancers hiding in the brain
• T cell immunotherapy trials to treat patients with hematological or solid tumor cancers
• Correction of hemophilia by genetic editing of liver stem cells
• Use of selected and expanded T cells to attack cancer stem cells and treat cancer
The City of Hope ASCC is implemented in a dedicated outpatient clinic in the City of Hope Day Hospital. In this setting, the novel research treatments are being done by clinical nurses rather than by research nurses working in a separate clinical research unit, as is normally done. We coined this new concept as “hybrid nurse.” In addition, we now have a nurse educator, who is directly involved in teaching of patients, families, and the ASCC staff. Together with the Patient Care Coordinator, the nurse educator develops the materials necessary to educate the “hybrid nurses” in understanding research protocols and research procedures within their area of expertise, while continuing to expand the various nursing capabilities. The set-up of our clinic enables evaluation of innovative stem cell-based therapies, and allows such treatments to be evaluated in the actual site where, if successful, they will become standard-of-care. Furthermore, to support the increasing numbers of clinical trials in the area of stem-cell based therapy, the City of Hope ASCC team has grown in the third year of funding, and now includes nursing staff, a patient care coordinator, a nurse educator, study coordinators, regulatory staff, and other personnel.
Thus, the COH ASCC is an experiment in itself, as it tests whether this hybrid research unit, in which a nurse must have research and clinical skills, is the best approach to introduction of new stem cell treatments to the clinic. In 2017, we organized the 2nd CIRM ASCC Network Annual Symposium that raised awareness about Alpha Clinics and brought together stakeholders to review the delivery of stem cell-based therapies for conditions with unmet medical needs.
CIRM funding has made it possible to bring clinical and research staff together, and in this way to accelerate development of stem cell research.
Reporting Period:
Year 4
In the fall of 2018, the City of Hope Alpha Stem Cell Clinic (ASCC) transitioned from the outpatient Day Hospital to the COH Clinical Research Unit (CRU). This unit's home is the Judy & Bernard Briskin Center for Clinical Research (BCCR), a newly renovated, modern facility that brings together clinical research services, treatments and the respective multidisciplinary teams, including pharmacy, phlebotomy, and specimen processing. The COH ASCC leadership and Research Operations, and the Day Hospital staff staff worked together on making this transition as smooth as possible for all studies, patients and the clinical and research staff involved. The BCCR includes 17 infusion areas, two nursing stations, and three exam and procedure rooms, an onsite pharmacy and lab services, a dedicated registration site, and direct connection to biospecimen coordination services. In its new home, the ASCC continues to benefit from nursing staff with competencies in: 1) drug clinical trials, including PK studies and antibody infusions; 2) management of very sick patients, and 3) efficient implementation of complex research protocols.
During the reporting period since 04/01/18, we approved the implementation of 16 new clinical trials.
Together with the COH Dept. of Professional Practice and Education and the other ASCCs in the CIRM Network, we organized the national conference entitled “The Critical Role of Nursing in Cellular Therapies” in August 2018. This conference was followed by a series of webinars presented by each of the ASCCs in the CIRM network, who featured clinical trials evaluating stem cells and lessons learnt. Participants who completed the symposium and five ASCC-led webinars received continuing nursing education credits and a certificate of training program completion. This program has been a success across the CIRM ASCC Network, and a second nursing education symposium will be organized in the spring of 2020.
Overall, the COH ASCC had a year of growth in clinical trial activity as well as educational initiatives.
Reporting Period:
Year 5
In the fall of 2018, the City of Hope Alpha Stem Cell Clinic (ASCC) started to transition from the outpatient Day Hospital to the COH Clinical Research Unit (CRU). During this reporting period we finalized the transition. This unit's home is the Judy & Bernard Briskin Center for Clinical Research (BCCR), a newly renovated, modern facility that brings together clinical research services, treatments and the respective multidisciplinary teams, including pharmacy, phlebotomy, and specimen processing. The COH ASCC leadership and Research Operations, and the Day Hospital staff staff worked together on making this transition as smooth as possible for all studies, patients and the clinical and research staff involved. The BCCR includes 17 infusion areas, two nursing stations, and three exam and procedure rooms, an onsite pharmacy and lab services, a dedicated registration site, and direct connection to biospecimen coordination services. In its new home, the ASCC continues to benefit from nursing staff with competencies in: 1) drug clinical trials, including PK studies and antibody infusions; 2) management of very sick patients, and 3) efficient implementation of complex research protocols. During the reporting period since 04/01/19, we approved the implementation of 3 new clinical trials and are currently working on implementing CoVID-19 studies throughout the ASCC network.
Reporting Period:
supplement period
City of Hope Alpha Clinics team has been continuing their effort in conducting cell and gene therapy during this award period. Additionally, the team put together a strong application for the CIRM Alpha Clinics Network Expansion award in June and was awarded $8M for the next 5 years. The new COH Alpha Clinics will be led by Dr. Leo Wang. Dr. John Zaia will continue his involvement as the Chair of the Advisory Council. We look forward to work with CIRM and our network partners to accelerate world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and world.
Grant Application Details
Application Title:
The Innovation-Alpha Clinic for Cellular Therapies (I-ACT) – A Program for the Development and Delivery of Innovative Cell-based Treatments and Cures for Life-threatening Diseases.
Public Abstract:
As the largest provider of bone marrow cell transplants in California, and the second largest in the nation, our institution has great expertise and an excellent record of safety in the delivery of stem cell treatments. We now propose to create the Alpha Clinic for Cell Therapy and Innovation (ACT-I) in which new, state-of-the-art, stem cell treatments for cancer and devastating blood-related diseases will be conducted and evaluated. As these experimental therapies prove to be effective, and become routine practice, our ACT-I Program will serve as the clinical center for delivery of these treatments. ACT-I will be an integral part of our Hematologic Malignancy and Stem Cell Transplantation Institute, placing it in the center of our institutional strengths, expertise, infrastructure and investment over the next decade. To move quickly once the CIRM award is made, ACT-I can be launched within our institution’s Day Hospital, a brand new, outpatient blood stem cell transplantation center opened in late 2013 with California Department of Health approval for 24 hour a day operation. This will ensure that ACT-I will have all the clinical and regulatory expertise, trained personnel, state-of-the-art facilities and other infrastructure in place to conduct first-in-human clinical trials and to deliver future, stem cell-based therapies for cancer and blood-related diseases, including AIDS. When our new Ambulatory Treatment Center is complete in 2018, it will double our capacity for patient visits and allow for expansion of the ACT-I pipeline of new stem cell products in a state-of-the-art facility.
Beyond our campus, we operate satellite clinics covering an area that includes urban, suburban and rural sites. More than 17.7 million people live in this area, and represent some of the greatest racial and ethnic diversity seen in any part of the country. Our ACT-I is prepared to serve a significant, diverse and underserved portion of the population of California.
CLINICAL TRIALS. Our proposal has two lead clinical trials that will be the first to be tested in ACT-I. One will deliver transplants of blood stem cells that have been modified to treat patients suffering from AIDS and lymphoma. The second will use neural stem cells to deliver drugs directly to cancer cells hiding in the brain. These studies represent some of the new and exciting biomedical technologies being developed at our institution. In addition to the two lead trials, we have several additional clinical studies poised to use and be tested in this special facility for clinical trials. In summary, ACT-I is well prepared to accommodate the long list of clinical trials and begin to fulfill the promise of providing new stem cell therapies for the citizens of California.
Statement of Benefit to California:
California’s citizens voted for the California Stem Cell Research and Cures Act to support the development of stem cell-based therapies that treat incurable diseases and relieve human suffering. To achieve this goal, we propose to establish an Alpha Clinic for Cellular Therapies and Innovation (ACT-I) as an integral part of our Hematological Malignancies and Stem Cell Transplantation Institute, and serve as the clinical center for the testing and delivery of new, cutting-edge, cellular treatments for cancer and other blood-related diseases. Our institution is uniquely well-suited to serve as a national leader in the study and delivery of stem cell therapeutics because we are the largest provider of stem cell transplants in California, and the second largest in the country. According to national benchmarking data, our Hematopoietic Cell Transplantation program is the only program in the nation to have achieved survival outcomes above expectation for each of the past nine years. This program currently offers financially sustainable, research-driven clinical care for patients with cancer, HIV and other life-threatening diseases. CIRM funding will allow the ACT-I clinic to ramp up quickly, drawing upon institutionally established protocols, personnel and infrastructure to conduct first-in-human clinical trials for assessment of efficacy. As CIRM funding winds down, ACT-I will have institutional support to offer proven cellular therapeutics to patients. The lead studies at the forefront of the ACT-I pipeline of clinical trials focus on treatments for HIV-1 infection and brain tumors, two devastating and incurable conditions. These first trials are closely followed by a robust queue of other stem cell therapeutics for leukemia, lymphoma, prostate cancer, brain cancers and thalassemia.
Our long list of proposed treatments addresses diseases that have a major impact on the lives of Californians. Thalassemia is found in up to 1 in 2,200 children born in California; prostate cancer affects 211,300 men, and HIV-1 infection occurs in 111,000 of our citizens. From 2008 to 2010, 6,705 Californians were diagnosed with brain cancers, 4,580 of whom died. In considering hematological malignancies during this same period, 2,800 patients were diagnosed with Hodgkin lymphoma (416 died), 20,351 with non-Hodgkin lymphoma (6,241 died), 13,358 with leukemia (6,961 died), 3,900 with acute myelogenous leukemia (2,972 died), 2,129 with acute lymphoblastic leukemia (648 died) and 4,198 with chronic lymphocytic leukemia (1,271 died). Standard of care fails in many cases; mortality rates for patients with hematological malignancies range from 25% to 76%. Successful stem cell therapeutics hold the promise to reduce disease-related mortality while improving disease-related survival and quality of life for the citizens of California, and for those affected by these diseases worldwide.
