Background and Rationale
CLL patients with residual disease following upfront therapy have increased risk of relapse, shorter progression-free survival (PFS), and overall survival (OS). Consolidative therapy to treat residual disease has been shown to prolong response duration and PFS in these patients. Therefore, we are conducting a phase I trial wherein CLL patients with residual disease following initial upfront therapy will be treated with autologous CD19-targeted gene-modified T cells as a consolidative therapy.
We have developed a novel therapy for CLL by genetically modifying patients’ own T cells to target the B cell specific antigen CD19. While we have demonstrated that gene-modified T cells are a promising therapy for CLL patients with relapsed and chemotherapy-refractory disease, the emerging preclinical and clinical trial data suggest that the antitumor efficacy of T cell therapy is significantly enhanced in the minimal disease setting.
Patients who have achieved partial response (PR) or complete response (CR) with detectable minimal residual disease (MRD) following upfront therapy consisting of pentostatin, cyclophosphamide, and rituximab will be eligible for the trial. MRD status will be assessed by RT-PCR at the Molecular Pathology Department of Memorial Sloan-Kettering.
- To determine the safety of modified T cells in the upfront setting
- To assess the antitumor efficacy of modified T cell therapy
Eligible patients will initially undergo a leukapheresis procedure to obtain autologous T cells. Isolated T cells will be genetically modified to target CD19 and expanded at Memorial Sloan-Kettering’s Center for Cell Engineering. Once a sufficient number of gene-modified T cells is obtained, the patient will first receive cyclophosphamide conditioning chemotherapy followed by modified T cell infusion. All treatments will be administered on an outpatient basis at the Adult Day Hospital at Memorial Sloan-Kettering. Serial sampling of blood and bone marrow will be performed following treatment to assess toxicity, therapeutic effects, and survival of the genetically modified T cells.
For more information and to find out whether a patient is eligible for this study, please contact Dr. Jae Park at 212-639-4048. Patients who respond to the therapy will be returned to your care approximately three months after T cell therapy.