This open-label, single arm phase 1 trial aims to determine the safety and tolerability of anti-CD19 and anti-CD22 chimeric antigen receptor-expressing (CAR) T cells (CD19x22 CAR T) in adolescents and adults with relapsed/refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL). This trial will determine the maximum tolerated dose of CD19x22 CAR T cells using a standard 3+3 trial design.
Age: ≥ 16 years of age with no upper age limit. (NOTE: the first three subjects on this trial must be ≥ 18 years of age.)
Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr Virus (EBV)+ DLBCL of the elderly; OR
Primary mediastinal (thymic) large B cell lymphoma; OR
Transformation to DLBCL; OR
Age < 16 years of age.
Patients who are intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.
Patients with active, poorly controlled hydrocephalus defined as increase/worsening in symptoms (headaches, nausea/vomiting, lethargy, or neurological function with increased hydrocephalus noted on radiologic evaluation and/or need for CSF diversion. Note: If hydrocephalus is controlled after CSF diversion, patient may be eligible for the study. Only applicable to Cohort 3.
Patients with brainstem lesions. Only applicable to Cohort 3.
Single group
CD19x22 CAR T Cells
DrugAutologous peripheral blood mononuclear cells transduced with CD19x22 CAR T lentiviral vector.
Overall safety and tolerability of CD19x22 CAR T Therapy in CAR-naive and CAR-treated subjects
Assessed by Type, Frequency, and Severity of Adverse Events (AEs). All AEs, including laboratory abnormalities, will be graded using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading criteria.
Determine the Recommended Phase II Dose (RP2D) Level
Incidence and frequency of Grade 3-5 toxicity occurring within the dose limiting toxicity (DLT) period post CD19x22 CAR T infusion. Grades 3-5 adverse events (AEs) are defined as Severe, Life-Threatening, and Fatal.
Feasibility of Manufacturing CD19x22 CAR T
The feasibility of manufacturing the desired dose of anti-CD19x22 CAR T cells will be established using the percentage of patients for whom the desired dose of CAR T cells was successfully produced.
Evaluate Safety of Infusion
Percentage of study participants who receive CD19x22 CAR T infusion without infusion reaction
Evaluate Clinical Efficacy of CD19x22 CAR T
Clinical efficacy is defined through Lugano response criteria at Day +60 (Cohort 2 only), Day +90, 6 months, and 1 year. Efficacy will be stratified based on prior receipt of CAR T cell therapy.
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