PRIMARY OBJECTIVE:
I. To determine the effect of maintenance obinutuzumab on duration of response (partial
response [PR] or complete response [CR]) in patients with CD20+ B-cell primary central
nervous system lymphoma (PCNSL) who attain PR or CR to first-line treatment with high-dose
methotrexate-based chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate overall survival after PR or CR (overall survival [OS]-PRCR). II. To evaluate
neurocognitive function, quality of life, and neuroimaging as indicators of neurotoxicity.
III. Progression-free survival (PFS) and overall survival (OS) will be calculated.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I (MAINTENANCE THERAPY): Patients receive obinutuzumab intravenously (IV) on days 1 and 2
for the first cycle, and on day 1 for the subsequent cycles. Cycles repeat every 60 days for
2 years in the absence of disease progression or unacceptable toxicity.
ARM II (OBSERVATION): Patients undergo observation for a total of 2 years.
Inclusion Criteria:
- CD20+ B-cell primary central nervous system lymphoma (PCNSL) confirmed at the time of
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-based
chemotherapy regimen with or without brain radiotherapy; high-dose methotrexate is
defined 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; must have
achieved objective response (PR or CR/unconfirmed complete response [CRu]) to
first-line treatment
- Brain magnetic resonance imaging (MRI) documenting objective response must be obtained
within 30 days of study enrollment
- If CSF was positive for lymphoma cells at diagnosis or during first-line treatment
and/or a slit lamp examination was positive at diagnosis or during first-line
treatment, then the CSF and vitreal studies must have been repeated and must have
indicated CR; Note: CR requires complete disappearance of all enhancing abnormalities
on gadolinium-enhanced MRI; if CSF was positive for lymphoma cells at diagnosis or
during first-line treatment and/or slit lamp examination was positive at diagnosis or
during first-line treatment, then the CSF and vitreal studies must have been repeated
and must have indicated CR; for CRu, some patients will have a small but persistent
enhancing abnormality on MRI related to biopsy or focal hemorrhage; it is often
difficult to ascertain whether this represents a residual nidus of tumor or scar
tissue; if the abnormality does not change or slowly involutes without therapy and
corticosteroids, it is reasonable to categorize as a CRu; at the time CR/CRu is
determined, the patient should not have used corticosteroids 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 from date of ICF
signing
- Creatinine clearance > 30 mL/min (calculated according to institutional standards or
using Cockcroft-Gault formula), +/- 7 days from date of ICF signing
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 5 x ULN, +/- 7
days from date of ICF signing
- Platelet >= 75,000 cells/mm^3, +/- 7 days from date of ICF signing
- Hemoglobin > 9 g/dL, +/- 7 days from date of ICF signing
- Absolute neutrophil count > 1.5 x 10^3 cells/mm^3, +/- 7 days from date of ICF signing
- Surgically sterile or agree to use effective contraception using an adequate measure
of contraception such as oral contraceptives, intrauterine device, or barrier method
of contraception in conjunction with spermicidal jelly while receiving obinutuzumab
and >= 18 months after the last dose of obinutuzumab for women, and 180 days after the
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-Hodgkin
lymphoma
- Known hypersensitivity to any of the study drugs
- History of other malignancy that could affect compliance with the protocol or
interpretation of results
- Patients with a history of curatively treated basal or squamous cell carcinoma of
the skin or in situ carcinoma of the cervix are generally eligible; patients with
a malignancy that has been treated, but not with curative intent, will also 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 prior to study enrollment
- Major surgery within 4 weeks prior to study enrollment
- Known infection with human immunodeficiency virus (HIV)
- Known positive hepatitis serologies:
- Hepatitis B (HBV): patients with positive serology for hepatitis B defined as
positivity for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(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
deoxyribonucleic acid (DNA) negative and are willing to undergo ongoing HBV DNA
testing by real-time polymerase chain reaction (PCR); patients with positive
serology may be referred to a hepatologist or gastroenterologist for appropriate
monitoring and management
- Hepatitis C (HCV): patients with positive hepatitis C serology unless HCV
ribonucleic acid (RNA) is confirmed negative and may be considered for inclusion
in the 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 enrollment
