ALL has an incidence of 1.2 to 1.4 per 100,000 per year in Europe (Saltman, BMC Cancer 2015). Although 75%-90% of adult patients with ALL achieve complete remission (CR) following initial treatment, eventually most relapse. R/R ALL has a poor prognosis, with a median survival of 4-8 months (Hoelzer, Ann Oncol 2016). Ongoing studies at the National Cancer Institute (NCI) using anti-CD19 CAR T cells with CD28/CD3&zgr; signaling domains showed durable remissions in pediatric patients with R/R ALL and adults with R/R B cell malignancies (Lee, Lancet 2015; Kochenderfer, J Clin Oncol 2015). KTE-C19 is an autologous, anti-CD19 CAR T cell therapy that uses the same construct as the NCI studies, manufactured in a streamlined 6- to 8-day process. Here, we describe a phase 1/2 study evaluating KTE-C19 in adult patients with R/R ALL.
The primary objective is to evaluate efficacy of KTE-C19, assessed by overall CR rate (CR + CR with partial hematologic recovery). Key secondary objectives include duration of response, minimal residual disease-free rate, allogeneic stem cell transplant rate, OS, and safety. Exploratory objectives include pharmacokinetics, pharmacodynamics, and predictive biomarker analyses. Patients with R/R ALL will be treated with fixed-dose fludarabine and cyclophosphamide conditioning chemotherapy followed by a single infusion of KTE-C19 at a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Phase 1 will enroll 3-12 patients with the primary objective to evaluate the safety of KTE-C19. In phase 2, approximately 50 patients will be enrolled. Eligible patients will be ≥18 years with ≥5% marrow blasts, ECOG PS 0-1, and adequate bone marrow, renal, hepatic, and cardiac function. Patients with Ph+ ALL and low-burden central nervous system disease are eligible. Patients with Burkitt lymphoma or chronic myeloid leukemia in blast crisis, extramedullary disease only, active graft-versus-host disease, or clinically significant infection are not eligible. Accrual began in December 2015. The study is planned at approximately 25 sites in the US and EU. Clinical trial information: NCT02614066.
Clinical trial identification
Legal entity responsible for the study
B. Shah: Advisory Board, Speaker Fees, Honorarium: Celgene; Honorarium: Bayer, Plexus Communications and Baxalta; Speaker Fees: Spectrum and Pharmacyclics; Research Funding: Rosetta Genomics; Advisory Board: Acetilon and Pfizer. W. Wierda: GSK research, Celgene consulting. G. Schiller: Research Funding: Novartis, Karyopharm, Astellas, Spectrum, Bluebird, Array Pharmaceutical; Honoraria, Research Funding, Speakers Bureau: Amgen and Celgene; Honoraria, Research Funding: Sunesis. A. Bot, J.M. Rossi, Y. Jiang, L. Navale, S. Stout, J. Aycock, J. Wiezorek, R. Jain: Employment with Kite Pharma. All other authors have declared no conflicts of interest.