Clinical trials of more than 125 patients testing an investigational personalized cellular therapy known as CTL019 was done by University of Pennsylvania research team.

This personalized cellular therapy approach begins with patients' own immune cells, collected through a procedure similar to dialysis. The cells are then engineered in a laboratory and infused back into patients' bodies after being trained to hunt and kill their cancer cells. All patients who enroll in the trials have cancers that have progressed despite multiple conventional therapies.
Updated results of a CTL019 trial for children and young adults with relapsed, treatment-resistant acute lymphocytic leukemia who were treated at the Children's Hospital of Philadelphia (Abstract #380) includes data on 39 patients. The findings, which will be presented by Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics and director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia, build on the team's report on 25 pediatric and five adult patients which was published in the New England Journal of Medicine in October. Thirty six of 39 children (92 percent) achieved a complete response (CR) after receiving an infusion of the modified cells. After a median follow-up of six months, more than two-thirds (70 percent) of children who responded remained in remission and 75 percent were alive, including the first patient to receive the therapy, in the spring of 2012. These results were achieved with only 3 of the patients going on to receive stem cell transplant while in remission.
All pediatric patients who responded to the therapy experienced a cytokine release syndrome (CRS) within a few days after receiving their infusions - a key indicator that the engineered cells have begun proliferating and killing tumor cells in the body, but also a known potentially lethal type of toxicity. Patients who experience a CRS typically have varying degrees of flu-like symptoms, with high fevers, nausea, muscle pain, and sometimes, low blood pressure and breathing difficulties. Some patients require treatment with anti-cytokine agents and steroids to manage these symptoms.
The research team will also report the first results of a CTL019 study of patients with relapsed or refractory non-Hodgkin lymphomas (NHL) (Abstract #3087). In patients with follicular lymphoma (FL) or diffuse large B cell lymphoma (DLBCL) who received infusions of CTL019, assessments at three months after treatment revealed that all five FL patients (100 percent) and five out of 11 DLBCL patients (45 percent) responded to the therapy, including complete responses in four patients (80 percent) with FL and four patients (36 percent) with DLBCL. All patients who received infusions developed varying degrees of CRS. The longest complete response durations are ongoing, at 8.8 months for DLBCL and 7.4 months for FL; all other responses continue, as well. The findings will be presented by Jakub Svoboda, MD, an assistant professor of Medicine in the Abramson Cancer Center, on behalf of the Lymphoma Program under the leadership of the study's principal investigator, Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Associate Professor of Chronic Lymphocytic Leukemia and Lymphoma.
In updated results of the Penn research team's Phase II dose optimization study of patients with chronic lymphocytic leukemia (CLL) who were treated with CTL019 (Abstract #1982), 10 out of 24 (42 percent) patients responded to the cellular therapy. Of those, five (21 percent) had complete responses, and five (21 percent) had partial responses. After a median follow-up of nine months, overall survival was 68 percent. Eleven patients, including five who responded to the therapy, experienced a cytokine release syndrome (CRS), though the severity of CRS did not correlate with response. Patients in this trial were randomized to receive two different doses of modified cells. The findings revealed no association between with the amount of cells and greater toxicities, but the researchers say it is still unclear if the amount of cells will affect the response of CLL to CTL019. These results will be presented by David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in Penn's Abramson Cancer Center.
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In July 2014, the U.S. Food and Drug Administration granted CTL019 its Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric ALL, a step which is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if a therapy has demonstrated substantial advantages over available treatments. CTL019 is the first personalized cellular therapy to receive the designation.
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