CART

CART cells originate with the isolation of the patient's T cells via apheresis. These cells are then activated and modified to express a transgene that encodes a tumor-specific CAR. These cells are then expanded to achieve a clinically significant cell dose which will then be infused back into the patient.

2.1 Hypothesis 1. The infusion of CD19 with or without CD 22 targeted CAR T-cells in patients with high risk or R/R BCL will improve the overall response rates and survival outcomes. The choice of antigen target is determined by detailed flow cytometric profiling of biopsied lymphoma cells if possible. 2.

The co-expression of Epo-R in our CD19 CAR T-cells will allow endogenous or exogenous Epo levels to support survival and expansion of infused T cells, thus overcoming the issue of suboptimal T-cell expansion and persistence due to prior chemotherapies in patients with high risk or R/R DLBCL.

This is a single center, open label, phase 1 lead in to determine Recommended Phase 2 Dose (RP2D), followed by a phase 2 trial to evaluate the safety and efficacy of Epo-R-CD19 CAR T with or without CD22 CAR T-cells infused into patients with B cell lymphoma.

The study will have the following parts: * Screening * Pre-infusion (cell product preparation and bridging) and infusion (lymphodepletion) * Primary efficacy endpoints * Long term follow up Patients who have high risk B cell lymphoma or relapsed/refractory B cell lymphoma who fufil the trial inclusion and exclusion criteria will undergo leukapheresis following trial enrollment.

Live record on ClinicalTrials.gov →

• Age 10 to 80 years at screening
• PET-CT measurable disease by Lugano classification (Deauville score of ≥4) and
• Tissue biopsy of any tumour site and flow cytometry study of CD19 and CD22 expression.
• Relapsed B-cell lymphoma after one line of systemic therapy or autologous bone marrow transplant. This includes DLBCL, PMBCL, HGBCL, DLBCL arising from indolent lymphoma, Burkitt's lymphoma/leukemia, Mantle cell lymphoma.
• High risk B-cell lymphoma (BCL). High risk BCL is defined by any of the criteria below:
• High-risk genetics - double/triple hit or p53mut or deletion.

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.