This is an open label, multi-center, phase Ib/II trial of Pembrolizumab, Ibrutinib and Rituximab in participants with recurrent Primary Central Nervous System Lymphoma.~A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose(s) of the investigational intervention to use for further studies.~Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. The dose of investigational intervention in Phase II will depend on the results from Phase Ib~Investigational means that the intervention is being studied.~The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab, ibrutinib or rituximab for recurrent primary central nervous system lymphoma (PCNSL) but these have been approved for other uses including other types of non-Hodgkin's lymphoma.~Pembrolizumab (MK-3475) has been studied in lab experiments and in other types of cancer, and information from these studies suggests that Pembrolizumab may be beneficial in this type of cancer. Pembrolizumab is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients; an antibody that is made in the lab is also known as humanized monoclonal antibody that is designed to block the action of the receptor, PD-1. PD-1 works to help tumor cells continue to grow and multiply. There are now several approved antibodies for the therapy of cancer and other diseases.~Ibrutinib is a type of drug called a kinase inhibitor. It is believed to block a type of protein called a kinase that helps lymphoma cells live and grow. By blocking this, it is possible that the study drug will kill cancer cells or stop them from growing.~Rituximab is a type of drug called a monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. Rituximab works with the immune system and has shown evidence for clinical activity when administered in combinations to treat lymphoma.~The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.~The three drugs being used in the study are:~Pembrolizumab (MK3475)~Ibrutinib~Rituximab (or biosimilar)~Participants will receive study treatment for up to 2 years as long as they do not have serious side effects and their disease does not get worse. Once off study, participants will be followed every 3 months for the rest of their life.~Phase I Enrollment: Approximately 9 to 12 participants~Phase II Enrollment :Approximately 25 patients~Merck & Co., Inc, a pharmaceutical company, is supporting this research study by providing funding for the research study and the study drug, Pembrolizumab (MK-3475)
This research study is evaluating a combination therapy of 3 drugs as possible treatments for recurrent primary central nervous system lymphoma (PCNSL).~The three drugs being used in the study are:~Pembrolizumab (MK3475)~Ibrutinib~Rituximab (or biosimilar)