Diffuse large B-cell Lymphoma (DLBCL) is 30%-58% of all NHL and has an incidence of 3.8/100,000 in Europe (Tilly et al, Ann Oncol 2015). KTE-C19 is an autologous anti-CD19 CAR T cell therapy with CD28/CD3&zgr; signaling domains centrally manufactured using a streamlined 6-8–day process (Better et al, ASCO 2014). The multicenter phase 1 portion of ZUMA-1 found that KTE-C19 was safe for further study in refractory, aggressive NHL. Toxicities include generally reversible cytokine release syndrome and neurotoxicity. The phase 1 overall response rate (ORR) was 71%; complete remission (CR) rate was 57% (Locke et al, ASH 2015). Here, we describe the enrolling phase 2 portion of ZUMA-1.
Approximately 112 patients with refractory, aggressive NHL will be enrolled into cohort 1 (approximately 72 patients with DLBCL) or cohort 2 (approximately 40 patients with primary mediastinal large B cell lymphoma or transformed follicular lymphoma). Patients will receive a fixed dose of 30 mg/m2/day fludarabine and 500 mg/m2/day cyclophosphamide conditioning chemo (chemo) x 3 days followed by a single infusion of KTE-C19 at a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Eligible patients will have chemo-refractory disease (progressive disease [PD] or stable disease to most recent chemo or PD/recurrence ≤12 months of prior autologous stem cell transplant), ≥18 years old, ECOG PS 0-1, adequate marrow, renal, hepatic, and cardiac function, and prior anti-CD20 monoclonal antibody and an anthracycline-containing chemo regimen. 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 are ineligible. The primary objective is to evaluate KTE-C19 efficacy by ORR (CR + partial remission). Key secondary objectives include duration of response, progression-free survival, overall survival, safety, pharmacokinetics, pharmacodynamics, and predictive biomarker analyses. The study is planned at approximately 25 sites in the US and EU. Accrual began November 2, 2015.
Clinical trial identification
Legal entity responsible for the study
S.S. Neelapu, U. Farooq: Research funding from Kite Pharma. F.L. Locke: Scientific advisory for Kite Pharma. N.L. Bartlett: Scientific advisory for Gilead. T. Siddiqi: Speaker's bureau for Pharmacyclics, Janssen, and Seattle Genetics. A. Goy: Honoraria, consultancy, speaker's bureau for Pharmacyclics and Johnson and Johnson; Honoraria and consultancy for Celgene, Takea, and Acerta; Consultancy for Infinity. D. Miklos: Research funding from Kite Pharma, Pharmacyclics, Janssen, Roche, Genentech, Novartis, Adaptive Biotechnology; scientific advisory for Pharmacyclics, Novartis, Seattle Genetics, and BMS; speaker's honoraria for Sanofi. I. Flinn: Research funding from Pharmacyclics and Janssen. L. Navale, J. Wiezorek, W.Y. Go: Employment with Kite Pharma. M. Elias: Employment from Kite Pharma. All other authors have declared no conflicts of interest.