1. Fuerst, Mark L.

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SAN DIEGO-The success of the first global pediatric trial of chimeric antigen receptor (CAR) T-cell therapy may lead to the availability of a commercial product as soon as next year.

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At the American Society of Hematology annual meeting, researchers presented findings from the phase II ELIANA clinical trial evaluating the efficacy and safety of CTL019, an investigational CAR T-cell therapy in relapsed/refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). They found that 82 percent of infused patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) at 3 months post CTL019 infusion (Abstract 221).


For all patients with complete remission, no minimal residual disease was detected. In addition, the estimated relapse-free rate among responders was 60 percent 6 months after infusion with CTL019.


"These global multicenter trial data build on earlier encouraging research conducted at a single trial site, and advance the case for CTL019 as a potential treatment for children and young adults with relapsed or refractory B-cell ALL," said lead author Stephan Grupp, MD, PhD, Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and Director of the Cancer Immunotherapy Frontier Program at the Children's Hospital of Philadelphia.


The results set the stage for filing CTL019 with the FDA in early 2017 for pediatric and young adult patients with relapsed/refractory B-cell ALL.


ELIANA Trial Findings

ELIANA is the first pediatric global CAR T-cell registration trial with study enrollment having occurred across 25 centers in the U.S., E.U., Canada, Australia, and Japan. All patients had CD19 positive B-ALL with morphologic marrow tumor involvement at registration and were either primary refractory; chemo-refractory after first relapse, relapsed after second line therapy; or ineligible for allogeneic stem cell transplant.


CTL019 was manufactured from patient peripheral blood mononuclear cells in the U.S. at a centralized manufacturing facility and supplied to all sites. The primary endpoint of overall remission rate within 3 months and secondary endpoints were assessed by an independent review committee.


The trial has enrolled 62 patients, and Grupp reported on the first 50 patients; 41 of 50 patients (82%) had a remission. The CR rate was 68 percent and the CRi rate was 14 percent. The 6-month overall survival rate was 89 percent and the disease-free survival rate was 60 percent.


"There was high efficacy, with the primary endpoint met. All complete remissions were MRD-negative and durable," said Grupp.


Nearly half (48%) of patients 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.


Other adverse events included grade 3 neurological and psychiatric events in 15 percent of patients, including encephalopathy and delirium, with no grade 4 events seen.


In addition, 39 percent of patients experienced decreased appetite, 37 percent had pyrexia, 33 percent hypotension, 31 percent elevations in liver enzyme levels, 26 percent hypokalemia, and 23 percent hypoxia. Cytopenias that had not resolved by day 28 were seen in 37 percent of patients and infections were seen in 40 percent.


Two deaths occurred within 30 days of infusion, one from ALL and one from cerebral hemorrhage. There were no cases of cerebral edema, according to Grupp.


There were no new safety signals found compared to prior CTL019 data, he noted, adding that the previous single center data was confirmed in a worldwide multicenter trial.


"CTL019 offers a new option for pediatric and young adult patients with relapsed/refractory B-cell ALL," Grupp concluded.


Mark L. Fuerst is a contributing writer.


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