The purpose of the study is to investigate whether combination of obinutuzumab, lenalidomide, and high dose methylprednisolone in the treatment of Richter's Syndrome. The study will evaluate whether this regimen can reduce the amount of cancerous cells in your body. All of these agents are approved by the FDA Obinutuzumab is a protein molecule manufactured from a single cell population, has been approved by the Food and Drug Administration (FDA) for the treatment of CLL of SLL. Lenalidomide is for the treatment of patients with other blood cancers. Methylprednisolone is a type of steroid, and it is used in a wide variety of medical conditions. These agents and the combination of these agents are not approved for the treatment of Richter's Syndrome and are considered experimental.

This is a phase I trial to determine the safety and tolerability of the combination of obinutuzumab, lenalidomide, and HDMP for patients with RS. There is not a standard of care for patients with Richter's Syndrome (RS). Ten patients will be enrolled with RS diagnosed by histology or flow cytometry and CLL, regardless of prior treatment for either condition.

Inclusion Criteria:

• Histologic diagnosis of Richter's Syndrome (RS)
• No requirement nor restriction for prior therapy or stage
• Measurable disease: may include FDG avid lesion, lymph node greater than 1.5 cm in greatest diameter, or clonal large B-cells in peripheral blood or bone marrow.
• ECOG 0-2
• Adequate organ function
• Adequate bone marrow function

Lenalidomide-related inclusion criteria:

• Able to take aspirin (81mg or 325mg) daily, warfarin, low molecular weight heparin, or equivalent anticoagulation as prophylactic medication.
• All study participants must be registered into the mandatory REVLIMID REMS® program, and be willing and able to comply with the requirements of REMS®.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours prior to starting REVLIMID® and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking REVLIMID®. FCBP must also agree to ongoing pregnancy testing.
• Males must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Known hypersensitivity to any of the study drugs
• Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for 2 years prior to enrollment.
• Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of treatment
• Major surgery within 4 weeks prior to the start of treatment
• Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1) seropositive status
• Positive hepatitis serology
• Women who are pregnant or lactating
• Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment
• Uncontrolled diabetes mellitus
• Myocardial infarction within 6 months of starting study drug
• Other clinically significant heart disease