This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).
Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma
Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline.
No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells.
Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"
Autologous transplant within 6 weeks of planned CAR-T cell infusion.
Recipient of prior CAR-T cell therapy targeting CD19 outside of this protocol.
Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast).
Human immunodeficiency virus (HIV) seropositivity.
Sequential
Fludarabine
DrugGiven intravenously (IV)
Cyclophosphamide
DrugGiven intravenously (IV)
anti-CD19 CAR-T cells
Biological/VaccineSingle infusion
Proportion of participants with treatment-emergent adverse events (AEs)
Participants treated with conforming product who received the target doses of anti-CD19 CAR-T infusion will be included in the analysis. Proportion of participants with treatment-emergent adverse events of CAR-T in B-cell NHL, as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0), revised Cytokine Release Syndrome (CRS) grading criteria, and American Society for Transplantation and Cellular Therapy (ASTCT) immune effector cell (IEC) -associated neurotoxicity syndrome (ICANS) Consensus Grading for Adults (for neurotoxicity grading).
Proportion of participants who experience a dose-limiting toxicity (DLT) (Dose escalation)
A DLT includes AEs graded according to CTCAE version 5.0, with the exceptions of CRS and neurotoxicity, which are graded using CRS and ICANS criteria. DLTs must 1) be suspected to be secondary to CAR-T cell infusion, 2) occur during the first 30 days after infusion and 3) meet the following criteria: 1. Grade 3 or 4 non-hematologic toxicities of any duration, with following exceptions: Grade 3 laboratory abnormalities without associated symptomatology or clinical consequence that resolve in \< 7 days; AEs associated with Grade \<= 2 CRS; Toxicities associated with Grade 3 CRS (except cardiac or pulmonary organ toxicity) that improves to grade \<= 2 within 3 days of intervention; isolated renal or hepatic grade 3 organ toxicity that does not resolve within 7 days; Laboratory abnormalities compatible with tumor lysis syndrome; Grade 4 hematological toxicity that persists at grade \>= 3 despite maximum supportive care for \>21 days.
Proportion of participants with CAR-T infusion related adverse events (Dose Escalation)
The proportion of participants with adverse events related to the collection and infusion of CAR-T cells targeting CD19 will be reported.
Proportion of participants with delayed infusion due to study-related adverse events
The proportion of participants who have their infusion delayed due to and AE will be reported.
Overall Response Rate (ORR)
Overall response rates will be reported as proportions of participants by arm. The 2014 Lugano Response for Malignant Lymphoma criteria will be to determine response: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Relapse and Progression (PD). For the Waldenstrom's Macroglobulinemia cohort, the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) response criteria will be used to determine response: CR, very good partial response (VGPR), PR, minor response (MR), SD, and PD.
Complete Response Rate
Complete response rates will be reported as will be reported as proportions of participants by arm.
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C. Babis Andreadis
Lead sponsor
University of California, San Francisco
Sponsor institution
University of California, Davis
Collaborator
