Clinical Trials

Date: 2016-12-04

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 58th American Society of Hematology (ASH) Annual Meeting

Company: Novartis (Switzerland)

Product: CTL019 - tisagenlecleucel-T

Action mechanism: cell therapy/gene therapy/CAR-T cell therapy. CTL019 is an investigational, personalized T cell therapy, which was pioneered by Carl June and his team at Penn. In a CTL019 treatment cycle, immune cells (T cells) are drawn from a patient's blood. Then, using CAR technology, the T cells are reprogrammed to "hunt" cancer cells that express specific proteins, called CD19. CD19 is associated with a number of B-cell malignancies including ALL, CLL, diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. When the T cells are re-introduced into the patient's blood, the cells proliferate and bind to the targeted cancer cells and destroy them. These autologous T cells transduced with lentiviral vector containing a chimeric antigen receptor directed against CD19 were previously known as CART19. In July 2014, the FDA designated  CTL019 as a Breakthrough Therapy for the treatment of pediatric and adult patients with r/r ALL under the Penn IND. Novartis and Penn have an exclusive global agreement to research, develop and commercialize personalized CAR T cell therapies for the treatment of cancers. Novartis holds the worldwide rights to CARs developed through the collaboration for all cancer indications, including the lead program CTL019.

Disease: B-cell acute lymphoblastic leukemia

Therapeutic area: Cancer - Oncology

Country: Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Norway, Spain, USA

Trial details: This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL. (NCT02435849)

Latest news: * On December 4, 2016, Novartis has presented results from first global registration trial (ELIANA) of CTL019 in pediatric and young adult patients with  relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) at the 58th American Society of Hematology (ASH) annual meeting (Abstract #221, December 3, 4:00-5:30 p.m.). The global Phase II study found that 82% (41 of 50) of infused patients achieved complete remission or complete remission with incomplete blood count recovery at three months post CTL019 infusion. For all patients with complete remission, no minimal residual disease was detected. In addition, the estimated relapse-free rate among responders was 60% (95% CI: 36, 78) six months after infusion with CTL019. The results set the stage for filing CTL019 with the FDA in early 2017 for pediatric and young adult patients with r/r B-cell ALL. ELIANA is the first pediatric global CAR T cell registration trial with study enrollment having occurred across 25 centers in the US, EU, Canada, Australia and Japan. Forty-eight percent of patients in ELIANA experienced grade 3 or 4 cytokine release syndrome (CRS), a known complication of the investigational therapy that may occur when the engineered cells become activated in the patient's body. CRS was managed on a global scale using prior site education with implementation of the CRS treatment algorithm. There were no deaths due to CRS. Fifteen percent of patients experienced grade 3 neurological and psychiatric events including encephalopathy and delirium, with no grade 4 events seen. In addition to filing CTL019 for approval with the FDA in early 2017, Novartis plans to file with the European Medicines Agency (EMA) later in 2017. The investigational therapy received PRIME (PRIority MEdicines) designation from the EMA earlier this year.

Is general: Yes