Children’s Health and UT Southwestern Medical Center are proud to be among 25 sites in the United States, European Union, Canada, Australia, and Japan that participated in the Novartis-sponsored ELIANA study of a groundbreaking cancer therapy.

The ELIANA study was the first global clinical trial of CAR-T cell therapy, now the first gene therapy to be approved by the US Food and Drug Administration (FDA).  The trial evaluated the efficacy and safety of anti-CD19 engineered T-cells for the treatment of refractory/relapsed acute lymphoblastic leukemia (ALL) in pediatric patients.  CTL019 therapy, now named Kymriah, earned Fast Track, Priority Review, and Breakthrough Therapy designations from the FDA, leading up to FDA approval on August 20, 2017.  This historic action makes Kymriah the first gene therapy available to patients in the US, opening a new era of cancer treatment. 

This approach to immunotherapy involves collecting a patient’s own T cells through apheresis and genetically engineering the cells to express anti-CD19 chimeric antigen receptors that can recognize and attack tumor cells that express CD19 surface antigen.  After these living cells are grown in a laboratory, they are infused into the patient and begin their work to kill the cancer cells that express the antigen.  CTL019 represents the first FDA approval of chimeric antigen receptor based therapy for any cancer.

ALL accounts for roughly 25% of pediatric cancer diagnoses in children younger than 15 years of age, making it the most common childhood cancer.  Approximately 85-90% of kids who are diagnosed with B-cell ALL can be cured through standard treatment with intensive chemotherapy.  However, for patients who relapse or do not respond to conventional treatments, the options were extremely limited and less than half of these children survived.  In the data submitted to the FDA from the ELIANA study, 83% of patients who received CTL019 achieved complete remission.

CTL019 therapy was not without issues: Patients who received CTL019 were at risk of side effects, including cytokine release syndrome, in which patients have high fevers and in more severe cases need ICU-level care. But overall the results of the ELIANA trial represented a remarkable leap forward.

This clinical trial has truly been a collaborative effort across our campus, involving physicians, advanced practice providers, nurses, research coordinators, pharmacists, medical assistants, technicians, and administrators from the CCBD, Radiology, ICU, Emergency Room, Laboratory, and Stem Cell Lab. We are grateful to the entire team from Children’s Health, UT Southwestern, and Carter Blood Care that made this study possible here, and most of all to the patients and families who participated.

REFERENCES:

Novartis Global (2017). Novartis announces first CAR-T cell therapy BLA for pediatric and young adult patients with r/r B-cell ALL granted FDA Priority Review [Press release].  Retrieved from https://www.novartis.com/news/media-releases/novartis-announces-first-car-t-cell-therapy-bla-pediatric-and-young-adult

Novartis Global (2017).  Novartis CAR-T cell therapy CTL019 unanimously (10-0) recommended for approval by FDA advisory committee to treat pediatric, young adult r/r B-cell ALL [Press release]. Retrieved from https://www.novartis.com/news/media-releases/novartis-car-t-cell-therapy-ctl019-unanimously-10-0-recommended-approval-fda

U.S. Food and Drug Administration (2017).  FDA approval brings first gene therapy to the United States: CAR T-cell therapy approved to treat certain children and young adults with B-cell acute lymphoblastic leukemia [Press release]. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm