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

1. Confirmed treatment-naïve de novo CD20+ DLBCL, regardless of cell of origin, with Stage II-IV disease, or Stage I disease if 6 cycles of chemotherapy are planned.
2. Measurable disease on cross section imaging that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions
3. Appropriate candidate for systemic immune-chemotherapy such as the standard RCHOP21 6 cycles as determined by the treating physician
4. Age >/=18
5. Adequate organ function (normal cardiac ejection fraction of >45%, serum bilirubin \<1.5 mg/dl, AST or ALT \</= 5 x ULN, and creatinine clearance > 30 mL/min (Calculated according to Cockcroft - Gault formula) unless due to lymphoma with documentation of normal function prior to onset of lymphoma. In the case of Gilberts Syndrome, or documented liver or pancreatic involvement by lymphoma, the requirement for total bilirubin is \</=5.0 mg/dl
6. ANC >1000/mm3, hemoglobin >8.0, and platelets >100,000/mm3. If bone marrow is involved with lymphoma and normal marrow function prior to onset of lymphoma is documented: ANC of >750, any hemoglobin, and platelets of >50,000/mm3.
7. Performance status \<3 (unless previous performance status was 0 or 1 and deterioration is due to lymphoma which treating MD expects to reverse with therapy)
8. Consent to potential need for transfusion of blood products
9. Able to give informed consent
10. Ability and willingness to comply with the requirements of the study protocol

Exclusion Criteria:

1. Prior history of low grade lymphoma with transformation to DLBCL. If a patient has a composite diagnosis of DLBCL and low grade without a prior history of lymphoma, they will not be considered ineligible.
2. Pregnant or lactating females
3. Symptomatic CNS lymphoma involvement
4. Significant comorbidity (cirrhosis, severe coronary artery disease, significant psychiatric illness, or other that may compromise the ability to safely administer the therapy at the discretion of the primary investigator)
5. HBV: Patients with positive serology for Hepatitis B defined as positivity for HBsAg or anti-HBc. Patients who are positive for anti-HBc may be considered for inclusion in the study on a case-by-case basis if they are hepatitis B viral DNA negative and are willing to undergo ongoing HBV DNA testing by real-time PCR. Patients with positive serology may be referred to a hepatologist or gastroenterologist for appropriate monitoring and management.
6. Hepatitis C (HCV): Patients with positive hepatitis C serology unless HCV RNA is confirmed negative and may be considered for inclusion in the study on a case-by-case basis.
7. Known HIV or HTLV infection
8. Previous malignancy with diagnosis or suspicion of recurrence within the past 2 years, not including non-melanoma skin cancers or in situ malignancies.
9. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
10. Known hypersensitivity to any of the study drugs
11. 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 Cycle 1
12. Major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
13. Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly.
14. Effective contraception is required while receiving obinutuzumab. For women, effective contraception is required to continue for >/= 12 months after the last dose of obinutuzumab. For men, effective contraception is required to continue for 3 months after the last dose of obinutuzumab treatment.
15. Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment
16. Peripheral neuropathy >/= Grade 2
17. Subjects who are unwilling to take VTE prophylaxis