by NCI Staff. HER2 is an important target for tumor gene therapy. Full Title A Phase I Clinical Trial to Evaluate the Safety and Tolerability of Mesothelin-specific Chimeric Antigen Receptor (CAR)-positive T-Cells in Patients with Metastatic Mesothelin-expressing Breast Cancer Purpose A protein called mesothelin is overexpressed in some breast cancers. HIGHLIGHTS • Rapid rise in initiated CAR-T/TCR clinical trials for the treatment of cancers • CD19 CAR-T products are driving the overall number of clinical trials • By the end of 2018, the number of active trials originated in China exceeded those in the US. The system, called Prodigy, is “closed,” meaning that once the collected cells from the patient are put into the system, it takes care of the rest, producing a completed CAR T-cell product within 2 weeks, explained Jason Yovandich, Ph.D., also of DCTD. And as researchers look to expand CAR T-cell therapy as an option for other cancers, including solid tumors, Dr. Welch said, lowering the barriers to their success will be critical. In CAR T-cell therapy, after patients undergo leukapheresis, their T cells are subject to a complex process that produces hundreds of millions of genetically modified T cells that they then receive via intravenous infusion. “You can’t just manufacture cells in any lab and give them to patients,” said Dr. Shah, who has led several trials of CAR T-cell therapies in children with blood cancers at the NIH Clinical Center in Bethesda, MD. Even when a CAR T-cell therapy is produced in house at a single institution, there are always logistics to deal with. For general information, Learn About Clinical Studies. Credit: Adapted from Blood Cancer Journal. “You need to have the infrastructure and the support and the knowledge to be able to do this well.”. Before you take part . Clinical trials look at new ways to prevent, detect, or treat disease. All trials on the list are supported by NCI. NCI’s basic information about clinical trials explains the types and phases of trials and how they are carried out. Studies have shown that overexpression of CD44v6 is an important factor for the invasion and metastasis of breast cancer, and is closely related to the tumor size of the breast cancer, tumor staging, and lymph node metastasis. Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information. In the case of permitted digital reproduction, please credit the National Cancer Institute as the source and link to the original NCI product using the original product's title; e.g., “NCI Initiative Aims to Boost CAR T-Cell Therapy Clinical Trials was originally published by the National Cancer Institute.”, November 10, 2020, Home About cancer Find a clinical trial A trial of CAR T-cell for people with T cell lymphoma (AUTO4-TL1) A trial of CAR T-cell for people with T cell lymphoma (AUTO4-TL1) Cancer type: Blood cancers. Only a doctor can refer and enrol you in a clinical trial. The progress made with CAR T-cell therapy in children with ALL "has been fantastic," said Terry Fry, M.D., a lead investigator on several POB trials of CAR T cells who is now at Children's Hospital Colorado. 1 . We included studies which focused on the association between CAR-T cell therapy and patient response rate and survival time in solid tumors. “That’s the idea we’re trying to support,” he said. All trials on the list are supported by NCI.. NCI’s basic information about clinical trials explains the types and phases of trials and how they are carried out. The final step in the manufacturing journey requires some important housekeeping to ensure the purity and quality of the CAR T cells, at which point they are ready to be infused back into the patient. Lymphoma. And with the NCI manufacturing initiative coming online, she added, “there was now a mechanism to think about a multicenter trial.”. Serious active infection during screening. History of prolonged or serious heart disease during QT. To search for an open CAR T trial at MSK, visit our clinical trial database. Clinical trials are research studies that involve people. First, a patient’s own blood is collected and the white blood cells from that collection are separated out, with the remaining red blood cells and plasma returned to the patient, a process known as leukapheresis. “That’s what it takes to put something like this together,” he said. Patients with stage III, IV or relapsed breast cancer confirmed by histology and biopsy. Once the collected white blood cells are in hand, research groups use various methods to isolate specific T cells from the other white blood cells. For all CAR T Inquiries (patient, physician, clinical trials) This specific CAR was initially developed by Terry Fry, M.D., formerly of the POB and now at the University of Colorado School of Medicine. The initial clinical trial supported by this effort will be the first trial to test a CAR T-cell therapy designed to target a protein on cancer cells called CD33 in children and young adults with advanced forms of acute myeloid leukemia (AML). Next, this small batch of CAR T cells is induced to multiply until they number in the millions, a process that is carefully monitored to ensure that they grow enough in number to achieve the appropriate “dose” of T cells. COVID-19 is an emerging, rapidly evolving situation. Anal cancer survivor: Go directly to MD Anderson. Other types of research studies. Individual Participant Data (IPD) Sharing Statement: Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Number of patients with adverse events. The clinical trials on this list are studying ROR1 CAR-specific Autologous T-Lymphocytes. NEW YORK – Mustang Bio and City of Hope announced on Monday that they have initiated a Phase I clinical trial evaluating … Multiple myeloma survivor grateful CAR T cell therapy clinical trial gives her another option. A Phase I Clinical Trial to Evaluate the Safety and Tolerability of Mesothelin-Specific Chimeric Antigen Receptor-Positive T Cells in Patients With Metastatic Mesothelin-Expressing Breast Cancer: Actual Study Start Date : June 2016: Estimated Primary Completion Date : June 2021: Estimated Study Completion Date : June 2021: Resource links provided by the National Library … Results. Once the collected white blood cells are in hand, research groups use various methods to isolate specific T cells from the … The survival time of the patients treated with the multi-4SCAR T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated. Then, a disarmed virus is used to deliver genetic instructions to the T cells telling them to produce the chimeric antigen receptor (CAR), which ends up on their surfaces, and co-stimulatory molecules, which reside inside the cell. Researchers at City of Hope have opened a first-in-human clinical trial to assess the use of chimeric antigen receptor T-cell therapy for … Breast cancer prevention trial underway. In addition, a growing number of immunotherapy clinical trials are in place to test this groundbreaking approach on other cancers like lymphoma, multiple myeloma, and for solid tumors, through trials in glioblastoma, mesothelioma, and ovarian and pancreatic cancer. Clinical trials offer the chance to try new treatments that may be more effective than standard treatments. “We’re still taking baby steps,” he said. Having multiple sites for the first trial will be good for both the investigators and the patients, said the trial’s co-lead investigator, Richard Aplenc, M.D., of CHOP, where the first patient on the trial was enrolled in January. In part, that’s because of the remarkable way they can eliminate cancer in some people with advanced blood cancers. Targeting therapies for GD2 may help improve the survival rate and cure rate of breast cancer patients. In breast cancer, we have small, slow-growing, indolent, idle cancers all the way to extremely aggressive cancers-- so that spectrum. Shah and Aplenc, whose work focuses on developing and testing treatments, including stem cell transplants, for children with blood cancers is highly collaborative, she said. Currently, we have many ongoing trials with additional trials expected to open in the new year. “We’re taking some of the risk out of [developing] innovative concepts and ideas by helping to bring more of these therapies into early clinical trials.”. Few laboratories and centers have the capability to make CAR T cells, which has limited the ability to test them more broadly. With an existing facility, the Biopharmaceutical Development Program (BDP) at the FNLCR in Frederick, MD, for manufacturing biological products, Dr. Welch said, there was an opportunity for NCI to help meet a critical need to help accelerate CAR T-cell research. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. The hope is that one day CAR-T cell therapy may also be a treatment for a variety of cancers, such as breast and colorectal cancer. The collaboration “has been tremendous and critical to the progress we have made.”, Deaths from Metastatic Melanoma Drop Substantially in the United States, Boosting Dendritic Cells Helps the Immune System Find Pancreatic Cancer, If you would like to reproduce some or all of this content, see Reuse of NCI Information for guidance about copyright and permissions. To confirm if CAR T cells still function in solid tumors, we have developed anti-CEA CAR-modified T cells. The location had already been identified: the BDP, which manufactures drugs and therapies from biological sources, such as bacteria and proteins, for research studies. Components of that blood are then used to create the treatment. It will ultimately enroll patients at six different sites, starting at the NIH Clinical Center in Bethesda, MD, and the Children’s Hospital of Philadelphia (CHOP). Similar results have been seen in trials of CD19-targeted CAR T cells led by researchers in CCR's Pediatric Oncology Branch (POB). To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Written, informed consent obtained prior to any study-specific procedures. Next, it was time to nail down the manufacturing process. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study. With a closed system, Dr. Yovandich said, “the only variable to account for is the patient cells going in.”. Studies have shown that overexpression of CD44v6 is an important factor for the invasion and metastasis of breast cancer, and is closely related to the tumor size of the breast cancer, tumor staging, and lymph node metastasis. The experts they consulted included David Stroncek, M.D., and Steve Highfill, Ph.D., of NIH’s Center for Cellular Engineering, which has extensive experience developing and manufacturing cell therapies, including CAR T cells, for investigators within NIH. Breast cancer is one of the most frequent cancer types in women. The average risk of a woman in the United States developing breast cancer in her life is about 13%. It has been reported that HER2 gene is overexpressed in 20% to 30% of breast cancer patients. The CAR T Cell Immunotherapy Breakthrough It’s also because of where they come from: a patient’s own blood. Find a clinical trial in cancer treatment at Princess Margaret. Some 330,000 American women are diagnosed with breast cancer each year, and researchers at Washington University School of Medicine in St. Louis are seeking ways to reduce that number. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1. Complementary & Alternative Medicine (CAM), Coping with Your Feelings During Advanced Cancer, Emotional Support for Young People with Cancer, Young People Facing End-of-Life Care Decisions, Late Effects of Childhood Cancer Treatment, Tech Transfer & Small Business Partnerships, Frederick National Laboratory for Cancer Research, Milestones in Cancer Research and Discovery, Step 1: Application Development & Submission, “underwent a dramatic regression” following the treatment, to treat a patient with an advanced form of leukemia, approved the first two CAR T-cell therapies, are rapidly developing new CAR T-cell therapies, Division of Cancer Treatment and Diagnosis (DCTD), Frederick National Lab for Cancer Research (FNLCR), children and young adults with advanced forms of acute myeloid leukemia (AML), Researchers Testing “Packaged” CAR T Cells for Retinoblastoma, Study Confirms HPV Vaccine Prevents Cervical Cancer, NCI Priorities in Reducing Global Cancer Burden, U.S. Department of Health and Human Services. 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