Despite treatment advances, chronic lymphocytic leukemia (CLL) remains largely incurable. First-line targeted therapy with ibrutinib produces durable remissions, but some patients discontinue treatment due to intolerance or disease progression.1 Prior research has indicated that autologous T-cells expressing a CD19-specific chimeric antigen receptor (CAR) with a CD28 costimulatory domain may be efficacious against CLL.2
KTE-X19 is an investigational, autologous, anti-CD19 CAR T-cell therapy that may offer longer durable remissions with manageable safety in patients with relapsed/refractory CLL. KTE-X19 is being evaluated in patients with relapsed/refractory CLL in the ZUMA-8 phase 1/2 multicenter study.
To be included in the study, adult patients were required to have relapsed/refractory CLL with ≥2 prior treatment regimens, disease progression with or intolerance to a Bruton’s tyrosine kinase inhibitor, Eastern Cooperative Oncology Group status 0 to 1, and adequate organ function. The phase 1 portion of the trial is expected to enroll 12 to 18 patients to assess dose-limiting toxicities. The phase 2 portion of the trial is expected to enroll approximately 60 patients to evaluate efficacy and safety. Patients will undergo leukapheresis followed by optional bridging therapy. Cyclophosphamide and fludarabine conditioning chemotherapy will be given on days –5, –4, and –3.
The primary end point is incidence of dose-limiting toxicities for phase 1 and Independent Review Committee–assessed objective response rate (ORR) per 2018 International Workshop on Chronic Lymphocytic Leukemia criteria for phase 2. Secondary end points in phase 2 include complete remission (CR) rate, investigator-assessed ORR, minimal residual disease (MRD) negativity rate, MRD-negative CR rate, duration of response, progression-free survival, overall survival, safety, and patient-reported outcomes. The ZUMA-8 study is currently enrolling patients at 30 sites in the United States and Europe.
Abstract TPS7566; Flinn I, et al.