ALL is the most common childhood malignancy; up to 20% of pts relapse after initial therapy, and have poor clinical outcomes (Hoffman and Gore. Front Oncol 2014). Promising results were observed with KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in B cell malignancies (Locke at al. AACR 2017, #9986). We present preliminary ZUMA-4 phase 1 results.
Pts aged 2-21 y with R/R ALL and adequate organ function received the planned dose of 1 or 2 × 106 CAR T cells/kg after low-dose conditioning chemotherapy (cyclophosphamide/fludarabine, CyFlu). Pts enrolled after the study’s dose-limiting toxicities (DLTs) portion receive tocilizumab ≤36 h after CAR T cell infusion. Phase 1 primary endpoint is the incidence of DLTs. Secondary endpoints include efficacy and biomarker assessments.
As of Dec 31, 2016, 4 of 5 enrolled pts have been treated; median follow-up, 5.3 mo (1.9-8.6). All pts had ≥2 prior lines of therapy and 1 pt had prior stem cell transplant (SCT). All pts received bridging chemotherapy due to high disease burden (baseline blasts, 41-99%) prior to KTE-C19. KTE-C19 was successfully manufactured in a centralized 6-7 d process across a range of baseline absolute lymphocyte counts (0.5–17.1 × 109/L) and CD4:CD8 ratios (0.1-0.7). KTE-C19 could not be manufactured for 1 pt who progressed with WBC >150,000/µL at apheresis and
KTE-C19 after low-dose CyFlu was tolerable and appears safe for further analysis in pediatric and adolescent pts with R/R ALL. KTE-C19 can induce deep remissions in heavily pre-treated pts with high disease burden. Based on these results, ZUMA-4 continues to enroll (NCT02625480).
Clinical trial identification
Legal entity responsible for the study
D.W. Lee: Honoraria from Juno. A.S. Wayne: Pfizer: Consultancy, Honoraria, advisory board; Kite Pharma: Research Funding, Honoraria, Advisory Board; NIH: Patents; MedImmune: Research Funding; Spectrum Pharmaceuticals: Research Funding; Spectrum: Honoraria, advisory board. R. Handgretinger: Patents and Royalties: Milteny Biotech. J. Rossi, Y. Jiang, L. Navale, S. Stout, J. Aycock: Employment/Stock Ownership: Kite Pharma. A. Mardiros: Employment/Stock Ownership: Kite Pharma; Patents: Mustang Bio. J. Wiezorek: Leadership/Employment/Stock Ownership: Kite Pharma. R. Jain: Patent/Employment/Stock Ownership: Kite Pharma. All other authors have declared no conflicts of interest.