Gray Zone Lymphoma

This phase I trial studies the side effects of polatuzumab vedotin when given with combination chemotherapy with or without glofitamab for the treatment of patients with untreated large B-cell lymphoma that grows and spreads quickly and has severe symptoms (aggressive). Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Glofitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Drugs used in combination chemotherapy such as etoposide, cyclophosphamide, and doxorubicin work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory drugs, such as prednisone, lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving polatuzumab vedotin in combination chemotherapy with or without glofitamab may help treat patients with aggressive large B-cell lymphoma.

The purpose of this study is to understand and determine if ruxolitinib added to pembrolizumab is safe and effective for the treatment of relapsed or refractory Hodgkin and non-Hodgkin lymphomas.