On December 7, 2015 Novartis reported that the latest findings from an ongoing Phase II study of CTL019, an investigational chimeric antigen receptor T cell (CART) therapy, further support its potential in the treatment of children and young adults with relapsed/refractory acute lymphoblastic leukemia (r/r ALL) (Press release, Novartis, DEC 7, 2015, View Source [SID:1234508479]).

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The study found that 55 of 59 patients (93%) experienced complete remissions (CR) with CTL019. These results will be presented in an oral session at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Monday, December 7 (Abstract #681, 3:15 p.m.)[1].

In the study, median follow up was 12 months, overall survival was 79% at 12 months (95% CI, 69-91%) and relapse-free survival was 76% at six months (95% CI, 65-89%) and 55% at 12 months (95% CI, 42-73%). Results found that 18 patients had ongoing CR after 12 months of therapy[1].

"This clinical trial of CTL019 is the largest study of a CART therapy in pediatric patients with relapsed or refractory acute lymphoblastic leukemia, and it is helping us better understand the therapy’s potential to achieve durable responses in this patient population," 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 (Penn), and director of Translational Research in the Center for Childhood Cancer Research at the Children’s Hospital of Philadelphia (CHOP). The ongoing study of CTL019 in pediatric patients with r/r ALL is being led by Dr. Grupp at CHOP and is sponsored by Penn.

Additionally, 52 of 59 (88%) patients developed Grade 1-4 cytokine release syndrome (CRS). CRS may occur after CTL019 infusion when the engineered cells become activated and multiply in the patient’s body. During CRS, patients typically experience varying degrees of flu-like symptoms with high fevers, nausea, muscle pain, and in some cases, low blood pressure and breathing difficulties. Treatment for CRS was required for hemodynamic or respiratory instability in 27% of patients and was reversed in all cases with an IL-6 receptor antagonist[1].

"We have observed pediatric patients in this study achieve complete remissions with CTL019 treatment, in many cases without stem cell transplantation, which underscores the potential for CTL019 to fill an unmet medical need," said Usman Azam, MD, Global Head, Cell & Gene Therapies Unit, Novartis Pharmaceuticals. "These new longer-term data add to the growing understanding of CTL019 for patients with relapsed or refractory acute lymphoblastic leukemia who run out of treatment options."

Novartis recently expanded its own global multisite Phase II clinical trial of CTL019 in pediatric r/r ALL with the opening of study sites in Europe, Canada and Australia. A list of participating trial centers is available at View Source (link is external).

Novartis and Penn have an exclusive global collaboration to research, develop and commercialize CART therapies for the investigational treatment of cancers. 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 Investigational New Drug application (IND). Breakthrough Therapy designation is intended to expedite the development and review of drugs that treat serious or life-threatening conditions if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. Novartis holds the worldwide rights to CARs developed through the collaboration with Penn for all cancer indications, including the lead program, CTL019.

Additional key CART data presented at ASH (Free ASH Whitepaper) include:

Findings from a study on treatment with CTL019 in children with r/r ALL that face additional central nervous system (CNS) relapse complications (Abstract #3769, December 7, 6-8 p.m.)[2]

Data on characterization and accurate early prediction of CRS in r/r ALL patients treated with CTL019 (Abstract #1334, December 5, 5:30 p.m.)[3]

Preliminary efficacy and safety data on humanized CTL119 in children with r/r ALL (Abstract #683, December 7, 3:45 p.m.)[4]
Preclinical data from a study on CART123 to mitigate toxicity in acute myeloid leukemia (Abstract #565, December 7, 10:30 a.m.)[5]

Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of uncertainty of clinical trials, there is no guarantee that CTL019 will ever be commercially available anywhere in the world.