A phase 1 clinical trial underway exclusively at Roswell Park Comprehensive Cancer Center will evaluate a novel chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed or refractory hematologic malignancies whose tumor cells express the CD19 protein, an emerging target in clinical cancer research.
Led by principal investigator Francisco Hernandez-Ilizaliturri, MD, Director of Lymphoma Research and Head of the Lymphoma Translational Research Lab at Roswell Park, the study involves CD19/28z armored CAR T therapy. Patients’ T cells will be collected and modified in two ways in the laboratory — first with the addition of a CAR to fortify their cancer-killing potential and then with a gene that “armors” them by stimulating them to produce the cytokine interleukin-12 (IL-12) — before they are reinfused in the patient. Preclinical studies have shown that the strategy could prove more effective and more durable than other treatment options.
“While about 40% of patients tend to do well on CAR T immunotherapy, in the other 60%, the cancer returns after treatment,” says 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 form of immunotherapy was developed by Roswell Park scientists in collaboration with scientists at Memorial Sloan Kettering Cancer Center. The T cells used in the trial will be manufactured in Roswell Park’s expanded state-of-the-art Good Manufacturing Practice (GMP) Engineering & Cell Manufacturing Facility for the first time.
The study, “Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T cells for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies” (NCT06343376), expects to recruit 36 patients ages 18 and older who have 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. Those in Cohort A will receive the EGFRt/19-28z/IL-12 CAR T cells. Those in Cohort B will undergo lymphodepletion chemotherapy with cyclophosphamide IV and fludarabine IV before receiving the T cells.
The study focuses on two primary outcome measures: incidence of adverse effects and maximal tolerated dose of the CAR T cells.
Roswell Park’s costs to conduct the clinical trial will be covered in full by the Roswell Park Alliance Foundation with funds raised through the ongoing Igniting Cancer Breakthroughs initiative.
