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.
Subjects must not have any signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at screening; subjects who have been previously treated for CNS disease, but have no evidence of disease at screening are eligible for this cohort.
Subjects must have disease progression confirmed by either flow cytometry or immunohistochemistry (IHC), disease stabilization, or disease recurrence after at least two lines of therapy.
Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
Mantle Cell Lymphoma (MCL).
Age < 16 years of age.
Patient who is intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.
History of other malignancies, unless they have been disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in situ and localized prostate cancer not on active treatment.
Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; uncomplicated infections are permitted if responding to active treatment.
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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