General Study Design. ZUMA-3 is a Phase 1/2, multicenter, open-label study evaluating the safety and efficacy of KTE-X19 in adult subjects with relapsed or refractory B-precursor ALL. In this study, relapsed or refractory is defined as one of the following: primary refractory; first relapse following a remission lasting ≤ 12 months; relapsed or refractory after second-line or higher therapy; relapsed or refractory after allogenic SCT (provided the transplant occurred ≥ 100 days prior to enrollment and that no immunosuppressive medications were taken ≤ 4 weeks prior to enrollment). During Phase 1, approximately 3-12 subjects with high burden [M3 marrow (>25% leukemic blasts) or ≥1000 blasts/mm3 in the peripheral circulation] r/r ALL disease who are evaluable for DLT will be assessed to evaluate the safety of KTE-X19. A SRT that is internal to the study sponsor, and in collaboration with at least 1 study investigator, will review safety data and make recommendations regarding further enrollment in Phase 1 or proceeding to Phase 2 based on the incidence of DLTs and overall safety profile of KTE-X19. Additionally, approximately 40 subjects with high or low burden disease may be enrolled to further assess safety (see Figure 1 and Section 9.6). During Phase 2, approximately 50 subjects in the mITT set will be assessed to evaluate the efficacy and safety of KTE-X19. In total, up to approximately 100 subjects may be enrolled and treated with KTE-X19 in the study in Phase 1 and 2 combined (see Section 9.6 and Section 10.5). During Phase 2, one interim and one primary analysis will be performed. The interim analysis is for safety only and will be performed by an independent DSMB after 20 Phase 2 subjects have been treated with KTE-X19 and had the opportunity to be followed for 30 days after the KTE-X19 infusion (see Section 10.7). Additional interim analyses for safety may be requested by the DSMB. The primary analysis will occur when the overall study enrollment is complete and the last treated subject in the mITT set has had the opportunity to complete the month 6 disease assessment (see Section 10.8). Each subject will provide consent and be evaluated for study participation. Once deemed eligible and enrolled into the study, each subject will follow the same study treatment schedule and procedural requirements, independent of the phase of the study, and proceed through the following study periods: • Screening period • Enrollment/Leukapheresis period • Bridging chemotherapy and CSF pro...
General Study Design. Study KTE-C19-102 is a Phase 2, multicenter, open-label study evaluating the safety and efficacy of KTE-X19 in subjects with r/r MCL. This study is designed to examine the safety and efficacy of KTE-X19 in patients who have r/r MCL that has progressed on prior chemotherapy, anti-CD20 antibody, and ibrutinib or acalabrutinib. The study will evaluate the XXX and durability of response after treatment with KTE-X19. An open-label, 2-cohort design is used, with a target XXX in the alternative hypothesis of 50% and a futility criterion that the XXX is no more than 25%. Up to approximately 130 subjects with r/r MCL in total will be enrolled and treated to evaluate the efficacy of KTE-X19. Cohort 1 will treat up to approximately 90 subjects at a target dose of CCI cells/kg, including up to approximately 80 KTE-X19 subjects and 10 axicabtagene ciloleucel subjects. The Cohort 1 KTE-X19 subjects will form the basis for statistical hypothesis testing on the primary endpoint. Cohort 2 will treat up to 40 KTE-X19 subjects at a target dose of CCI anti-CD19 CAR T cells/kg. Each subject will proceed through the following study periods: Screening Enrollment/Leukapheresis Bridging therapy, if applicable Conditioning chemotherapy Investigational product (IP) treatment Post-treatment assessment Long-term follow-up (LTFU) An independent DSMB will review safety and/or efficacy data 4 times during this study. The DSMB will first meet to review safety data when 10 Cohort 1 subjects have been enrolled and treated with anti-CD19 CAR T cells and followed for 30 days. The DSMB will meet for the second time to review safety and efficacy data after 20 Cohort 1 subjects have been enrolled and treated with anti-CD19 CAR T cells and have had the opportunity to complete the 3-month disease assessment. The DSMB will meet for the third time to review both safety and efficacy data after 10 subjects in Cohort 2 have been enrolled and treated with KTE-X19 and have had the opportunity to be followed for 30 days. The DSMB will meet for the fourth time to review safety data after 44 subjects in Cohort 1 have been enrolled and treated with anti-CD19 CAR T cells and have had the opportunity to be followed for at least 30 days, with focus on the safety data from the 6 KTE-X19 subjects treated most recently in this cohort. The DSMB will be chartered to make trial conduct recommendations based on an analysis of risk vs benefit. The DSMB may meet more often as needed. For details surroundin...
General Study Design. The proposed effort is designed to capture a variety of habitat types, provide broad spatial coverage, and to represent areas sampled in the original effort. As in the original 2002 study, three general zones representing the upper (zone 1), middle (zone 2) and lower (zone 3) portions of the river (approximately 7-kilometer-long segments of the May River) will be sampled (Figure 2). Within Zone 1, the following sampling sites will be identified: (1) two subtidal stations will be randomly located in the mainstem of the river for open-water sampling and oyster bar investigations,
