PHILADELPHIA — A University of Pennsylvania-developed personalized immunotherapy has been awarded the U.S. Food and Drug Administration’s Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL). The investigational therapy, known as CTL019, is the first personalized cellular therapy for the treatment of cancer to receive this important classification.

In early-stage clinical trials at the Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia, 89 percent of ALL patients who were not responding to conventional therapies went into complete remission after receiving CTL019.

“Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,” said the Penn research team’s leader, Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of Translational Research in the Abramson Cancer Center of the University of Pennsylvania. “Receiving the FDA’s Breakthrough Designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.”

The FDA’s Breakthrough Therapy designation, created in 2012, is intended to expedite the development and review of new medicines – both drugs and biologic agents – that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over available therapies. The FDA has previously granted Breakthrough Therapy to only four other biologic agents.

In August 2012, Penn announced an exclusive global research and licensing agreement with Novartis to further study, develop and commercialize personalized chimeric antigen receptor (CAR) T cell therapies for the treatment of cancers. Trials employing CTL019 began in the summer of 2010 in patients with relapsed and refractory chronic lymphocytic leukemia (CLL), and are now underway for adult and pediatric patients with ALL, and patients with non-Hodgkin lymphoma and myeloma. Penn and Novartis are also investigating the next generation of CAR therapies, with trials for mesothelioma, ovarian, breast and pancreatic cancer now in early stages.

During the 2013 annual meeting of the American Society of Hematology, the Penn research team announced study results of the first 27 ALL patients (22 children and five adults) treated with CTL019: 89 percent of the patients had a complete response to the therapy. The first pediatric ALL patient to receive the Penn therapy celebrated the second anniversary of her cancer remission in May, and the first adult patient remains in remission one year after receiving the therapy.

The investigational treatment pioneered by the Penn team begins by removing patients' T cells via an apheresis process similar to blood donation, then genetically reprogramming them in Penn’s Clinical Cell and Vaccine Production Facility. After being infused back into patients’ bodies, these newly built “hunter” cells both multiply and attack, targeting tumor cells that express a protein called CD19. Tests reveal that the army of hunter cells can grow to more than 10,000 new cells for each single engineered cell patients receive.

The adult ALL trials of CTL019 at the University of Pennsylvania’s Abramson Cancer Center are directed by David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the Abramson Cancer Center and Noelle Frey, MD, MSCE, an assistant professor of Medicine in the Abramson Cancer Center. The pediatric ALL trials are led by Stephan Grupp, MD, PhD, a professor of Pediatrics and director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. Bruce Levine, PhD, the Barbara and Edward Netter Professor in Cancer Gene Therapy in the department of Pathology and Laboratory Medicine, directs Penn’s Clinical Cell and Vaccine Production Facility.

Read more about the Breakthrough Therapy designation on the FDA website.