Maintenance Obinutuzumab in Treating Patients With Central Nervous System Lymphoma Who Have Achieved a Complete or Partial Response

Inclusion Criteria:

• CD20+ B-cell primary central nervous system lymphoma (PCNSL) confirmed at the timeof diagnosis by histology, cytology, or immunocytochemistry from cerebrospinal fluid (CSF); diagnosis must be documented by pathology report.

• Must have undergone first-line treatment with a high-dose methotrexate-basedchemotherapy regimen with or without brain radiotherapy; high-dose methotrexate isdefined as >= 3 grams/m^2; methotrexate dose reduction for creatinine clearance < 100 ml/min is permitted

• Must be within 75 days of completion of first-line treatment regimen at the time ofrandomization; must have achieved objective response (PR or CR/unconfirmed completeresponse [CRu]) to first-line treatment

• Brain magnetic resonance imaging (MRI) documenting objective response must beobtained within 30 days before randomization

• If CSF was positive for lymphoma cells at diagnosis or during first-line treatmentand/or a slit lamp examination was positive at diagnosis or during first-linetreatment, then the CSF and vitreal studies must have been repeated and must haveindicated CR; Note: CR requires complete disappearance of all enhancingabnormalities on gadolinium-enhanced MRI; if CSF was positive for lymphoma cells atdiagnosis or during first-line treatment and/or slit lamp examination was positiveat diagnosis or during first-line treatment, then the CSF and vitreal studies musthave been repeated and must have indicated CR; for CRu, some patients will have asmall but persistent enhancing abnormality on MRI related to biopsy or focalhemorrhage; it is often difficult to ascertain whether this represents a residualnidus of tumor or scar tissue; if the abnormality does not change or slowlyinvolutes without therapy and corticosteroids, it is reasonable to categorize as aCRu; at the time CR/CRu is determined, the patient should not have usedcorticosteroids for at least two weeks

• Karnofsky performance status (KPS) >= 60; Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2

• Signed informed consent form (ICF)

• Ability and willingness to comply with the requirements of the study protocol

• Total bilirubin < 3 x the upper limit of normal (ULN), ≤ 7 days before date ofrandomization

• Creatinine clearance > 30 mL/min (calculated according to institutional standards orusing Cockcroft-Gault formula), ≤ 7 days before date of randomization

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 5 x ULN, ≤7days before date of randomization

• Platelet ≤ 75,000 cells/mm^3, ≤ 7 days before date of randomization

• Hemoglobin > 9 g/dL, ≤ 7 days before date of randomization

• Absolute neutrophil count > 1.5 x 10^3 cells/mm^3, ≤ 7 days before date ofrandomization

• Surgically sterile or agree to use effective contraception using an adequate measureof contraception such as oral contraceptives, intrauterine device, or barrier methodof contraception in conjunction with spermicidal jelly while receiving obinutuzumaband >= 18 months after the last dose of obinutuzumab for women, and 180 days afterthe last dose of obinutuzumab for men

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

• Clinical evidence of extra-central nervous system (CNS) (systemic) non-Hodgkinlymphoma

• Known hypersensitivity to any of the study drugs

• History of other malignancy that could affect compliance with the protocol orinterpretation of results

• Patients with a history of curatively treated basal or squamous cell carcinoma ofthe skin or in situ carcinoma of the cervix are generally eligible; patients with amalignancy that has been treated, but not with curative intent, will also beexcluded, unless the malignancy has been in remission without treatment for >= 2years prior to randomization

• Known active bacterial, viral, fungal, mycobacterial, or other infection (excludingfungal infections of nail beds) or any major episode of infection requiringtreatment with IV antibiotics or hospitalization (related to the completion of thecourse of antibiotics) within 4 weeks prior to study randomization

• Major surgery within 4 weeks prior to study randomization

• Known infection with human immunodeficiency virus (HIV)

• Positive hepatitis serologies:

• Hepatitis B (HBV): patients with positive serology for hepatitis B defined aspositivity for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc); patients who are positive for anti-HBc may be considered for inclusionin the study on a case-by-case basis if they are hepatitis B viral deoxyribonucleicacid (DNA) negative and are willing to undergo ongoing HBV DNA testing by real-timepolymerase chain reaction (PCR); patients with positive serology may be referred toa hepatologist or gastroenterologist for appropriate monitoring and management

• Hepatitis C (HCV): patients with positive hepatitis C serology unless HCVribonucleic acid (RNA) is confirmed negative and may be considered for inclusion inthe study on a case-by-case basis

• Women who are pregnant or lactating

• Vaccination with a live vaccine a minimum of 4 weeks prior to study randomization