R/R MCL is an aggressive, generally incurable, B cell malignancy, representing approximately 6% of non-Hodgkin lymphomas with an incidence rate of 0.45/100,000 in Europe (Sant et al, Blood 2010). An ongoing study at the National Cancer Institute (NCI) using anti-CD19 CAR T cells with CD28/CD3&zgr; signaling domains showed durable remissions in patients with R/R B cell malignancies, including MCL (Kochenderfer et al, J Clin Oncol 2015; NCT00924326). KTE-C19 is an autologous, anti-CD19 CAR T cell therapy that utilizes the construct investigated in the NCI study and manufactured in a streamlined 6- to 8-day process. Here, we describe a phase 2 study evaluating KTE-C19 in patients with R/R MCL.
We plan to enroll approximately 70 patients with R/R MCL for treatment with a fixed dose of 30 mg/m2/day fludarabine and 500 mg/m2/day cyclophosphamide conditioning chemotherapy followed by a single infusion of KTE-C19 at a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Patients should have R/R disease with up to 5 prior therapies, which must have included an anthracycline- or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib. Additional inclusion criteria include age ≥18 years old, ECOG PS 0-1, and adequate marrow, renal, hepatic, and cardiac function. Patients with prior CAR T cell or other genetically modified T cell therapy, clinically significant infection, or current or history of central nervous system lymphoma or comorbidities are not allowed. The primary objective is to evaluate the safety and efficacy of KTE-C19, as measured by overall response rate (complete remission + partial remission). Key secondary objectives include describing duration of response, progression-free survival, overall survival, pharmacokinetics, pharmacodynamics, and predictive biomarker analyses. The study is planned at approximately 25 sites in the US and EU. Accrual began on November 9, 2015. Clinical trial information: NCT02601313.
Clinical trial identification
Legal entity responsible for the study
M. Wang: Research funding from Kite Pharma. F.L. Locke: Scientific advisory board for Kite Pharma. T. Siddiqi: Speaker's bureau for Pharmacyclics, Jannsen, and Seattle Genetics. B. Shah: Advisory board, speaker's bureau, honorarium from Celgene; honorarium from Bayer, Baxalta, Plexus Communications; speaker's bureau for Spectrum, Pharmacyclics; research funding from Rosetta Genomics; scientific advisory board for Acetilon, Pfizer. S. Forman: Patents with Mustang Therapeutics. T. Kipps: Consultancy, advisory, and research funding from AbbVie, Genentech, and Pharmacyclics. A. Bot, J.M. Rossi, L. Navale, Y. Jiang, J. Aycock, M. Elias, J. Wiezorek, W.Y. Go: Employment with Kite Pharma. All other authors have declared no conflicts of interest.