Clinical Trials

Date: 2014-12-06

Type of information: Presentation of results at a congress


Announcement: presentation of results at the 56th American Society of Hematology (ASH) annual meeting in San Francisco

Company: Novartis (Switzerland)

Product: CTL019 - tisagenlecleucel-T

Action mechanism: cell therapy/immunotherapy product/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.


 relapsed/refractory acute lymphoblastic leukemia in children and young adults

Therapeutic area: Cancer - Oncology - Rare diseases


Trial details:

Latest news: * On December 6, 2014, Novartis announced that findings from continued clinical studies of investigational chimeric antigen receptor (CAR) therapy, CTL019, demonstrate its potential role in the treatment of certain types of lymphocytic leukemia. In one long-term study of pediatric patients with acute lymphoblastic leukemia (ALL), results showed that 36 of 39 pediatric patients with relapsed/refractory (r/r) ALL, or 92%, experienced complete remissions (CR) with CTL019. These results, which will be presented in an oral session at the 56th American Society of Hematology (ASH) annual meeting in San Francisco, continue to increase scientific understanding of CTL019 (Abstract #380, December 8, 10:45 AM). "We're seeing pediatric patients who have not responded to any other therapy achieve complete remission as a result of treatment with CTL019," said lead investigator Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia (CHOP). "However, this is only the first step. Now that these patients have been followed for a longer period of time, we're seeing that a number of them remain in remission for one year or more. This leads me to believe the persistence and durability of CAR-modified cells may help protect against relapse." Additional highlights of the pediatric r/r ALL study include findings that patients have ongoing CR. Median follow-up was 6 months. Sustained remissions were achieved up to one year or more with 6-month event-free survival of 70% and overall survival of 75%, in most cases without further therapy. The probability of six-month CTL019 persistence was 68%, which was accompanied by B cell aplasia, a pharmacodynamic marker of CTL019 persistence and function[2]. Persistence of CTL019 cells detected by flow cytometry and/or qPCR, and accompanied by B cell aplasia, continued for up to 30 months after infusion in patients with ongoing responses. All responding patients developed cytokine release syndrome (CRS) at peak T cell expansion. Treatment for CRS was required for hemodynamic or respiratory instability in 33% of patients and CRS was managed with an IL-6 receptor antagonist, together with corticosteroids in five patients. These events were delayed, and few patients experienced infusional toxicities, including infusion-associated fever.

Is general: Yes