A Phase I/II Study of Lenalidomide and Obinutuzumab With CHOP for Diffuse Large B Cell Lymphoma

Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a study phase based on when you join this study. Up to 3 groups of up to 6 participants will be enrolled in Phase 1 of the study, and up to 50 participants will be enrolled in Phase 2. If you are enrolled in Phase 1, the dose of lenalidomide you receive will depend on when you join this study. The first group of participants will receive the highest dose level of lenalidomide. Each new group will receive a lower dose of lenalidomide than the group before it, if intolerable side effects are seen. This will continue until the most tolerable dose of lenalidomide is found. If you are enrolled in Phase 2, you will receive lenalidomide at the highest dose that was tolerated in Phase 1. All participants will receive the same dose of CHOP and obinutuzumab. Study Drug Administration: Each study cycle is 21 days. You will take lenalidomide pills by mouth on Days 1-14 of each cycle. You will receive obinutuzumab by vein over 3-4 hours on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2-6. You will receive cyclophosphamide by vein over about 1 hour on Day 1 of all cycles. You will receive doxorubicin and vincristine by vein over about 15 minutes each on Day 1 of all cycles. Study Visits: Within 3 days before Day 1 of Cycles 1-6: * You will have a physical exam. * Blood (about 8-9 teaspoons) will be drawn for routine tests and to check for PBMCs. One (1) time each week during Cycle 1 and then at any time the doctor thinks it is needed, blood (about 2-3 teaspoons) will be drawn for routine tests. At the end of Cycle 1 but before the start of Cycle 2, blood (about 6 teaspoons) will be drawn to check for PBMCs. At the end of Cycle 3 but before the start of Cycle 4, you will have a PET/CT scan. If you can become pregnant, blood (about 2-3 teaspoons) will be drawn for a pregnancy test 1 time before Cycle 1 and then 1 time during each cycle after that. Length of Treatment: You may receive lenalidomide, obinutuzumab, and CHOP therapy for up to 6 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on this study will be over after follow-up. End-of-Treatment Visit: Within 3-4 weeks after your last dose of study drugs: * You will have a physical exam. * Blood (about 8-9 teaspoons) will be drawn for routine tests and to check for PBMCs. * You will have a PET/CT scan. * If the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease. * If the doctor thinks it is needed and the tumor is accessible, you will have a core needle biopsy to check the status of the disease. To perform a core biopsy, a sample of tissue is removed using a hollow core needle that has a cutting edge. Follow-Up: Every 3 months (+/- 4 weeks) during the first year after the End-of-Treatment Visit and then every 4 months (+/- 9 weeks) during the second year: * You will have a physical exam. * Blood (about 2-3 teaspoons) will be drawn for routine tests. * You will have a PET/CT scan. This is an investigational study. Lenalidomide is FDA approved and commercially available for the treatment of multiple myeloma (MM) and myelodysplastic syndrome (MDS). Obinutuzumab is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). CHOP is FDA approved and commercially available for the treatment of lymphoma and non-Hodgkin's lymphoma. The combination of lenalidomide, CHOP, and obinutuzumab to treat DLBCL is considered investigational. Up to 59 participants will be enrolled in this study. All will take part at MD Anderson.