A phase 1 clinical trial is underway at Roswell Park Comprehensive Cancer Center to assess a novel chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed or refractory hematologic malignancies expressing the CD19 protein.
Led by Francisco Hernandez-Ilizaliturri, MD, Director of Lymphoma Research at Roswell Park, the study focuses on CD19/28z armored CAR T therapy. The approach involves collecting patients’ T cells and modifying them in the lab by adding a CAR to enhance their cancer-killing ability and a gene that stimulates the production of interleukin-12 (IL-12) to further "armor" them. These modified cells are then reinfused into the patient. Preclinical data suggests this strategy may be more effective and durable than current treatments.
Enhancing CAR T-Cell Therapy
"While about 40% of patients tend to do well on CAR T immunotherapy, in the other 60%, the cancer returns after treatment," explains Dr. Hernandez-Ilizaliturri. "Our approach is a further step in the development of this therapeutic platform in which CAR cells are not only engineered to recognize and kill cancer cells, but also re-engineered to secrete cytokines to recruit other immune cells, hopefully leading to better outcomes for patients with refractory lymphoma."
This enhanced immunotherapy was developed by Roswell Park scientists in collaboration with researchers at Memorial Sloan Kettering Cancer Center. The T cells used in the trial will be manufactured in Roswell Park’s Good Manufacturing Practice (GMP) Engineering & Cell Manufacturing Facility.
Trial Details
The study, titled "Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T cells for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies" (NCT06343376), plans to enroll 36 patients aged 18 and older with the following hematologic malignancies:
- Recurrent or refractory chronic lymphocytic leukemia
- Recurrent or refractory chronic diffuse large B-cell lymphoma
- Recurrent or refractory follicular lymphoma
- Recurrent or refractory high-grade B-cell lymphoma
- Recurrent or refractory mantle cell lymphoma
Patients will be assigned to one of two cohorts. Cohort A will receive the EGFRt/19-28z/IL-12 CAR T cells alone. Cohort B will undergo lymphodepletion chemotherapy with cyclophosphamide IV and fludarabine IV before receiving the T cells.
The trial's primary objectives are to determine the incidence of adverse effects and the maximum tolerated dose of the CAR T cells.
Funding for the clinical trial is provided by the Roswell Park Alliance Foundation through the Igniting Cancer Breakthroughs initiative.
