This randomized phase II trial studies how well obinutuzumab works as maintenance treatment in patients with central nervous system lymphoma who have achieved the disappearance of all signs of cancer in response to treatment (complete response) or a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment (partial response). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
28
Ancillary studies to evaluate neurocognitive function at study entry and at 2 years after study entry.
Given IV
Ancillary studies to evaluate quality of life at study entry and at 2 years after study entry.
Memorial Sloan Kettering Cancer Center
New York, New York, United States
NOT_YET_RECRUITINGCleveland Clinic
Cleveland, Ohio, United States
NOT_YET_RECRUITINGProvidence Health & Services; Providence Neurological Specialties
Portland, Oregon, United States
RECRUITINGPennsylvania State University
Hershey, Pennsylvania, United States
RECRUITINGUniversity of Vermont
Burlington, Vermont, United States
RECRUITINGUniversity of Virginia
Charlottesville, Virginia, United States
RECRUITINGIvy Center for Advanced Brain Tumor Treatment; Swedish Neuroscience Institute
Seattle, Washington, United States
RECRUITINGPartial response (PR) or complete response (CR) duration
PR or CR duration will be assessed using Kaplan-Meier product limit estimates and compared between patients with maintenance versus without obinutuzumab maintenance using the log-rank test. In addition, the Cox proportional hazard model will be used to estimate hazard ratios.
Time frame: From the date of brain magnetic resonance imaging (MRI) after completion of first-line treatment which confirms PR or CR, to disease progression or death, assessed up to 2 years
Overall survival (OS) after CR
OS after PR or CR will be assessed using Kaplan-Meier product limit estimates and compared between patients with maintenance versus without obinutuzumab maintenance using the log-rank test. In addition, the Cox proportional hazard model will be used to estimate hazard ratios.
Time frame: From the date of brain MRI after completion of first-line treatment which confirms PR or CR, to death, assessed up to 2 years
Neurocognitive function - Wechsler Adult Intelligence Scale
Will be measured by the Wechsler Adult Intelligence Scale. Scale range 0 to 16 Forward; 0 to 14 Backward. Higher the score means better outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: Up to 2 years
Quality of life (QOL) - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain Neoplasm 20-item
Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module-20 (EORTC QLQ-BN20) questionnaire. Scale 20 to 80 points. Higher score means worse outcome. Longitudinal data of QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: Up to 2 years
Progression free survival (PFS)
PFS will be assessed using Kaplan-Meier product limit estimates and compared between patients with obinutuzumab maintenance versus without maintenance using the log-rank test. Longitudinal data of neurocognitive function and QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: From the start date of first-line primary central nervous system lymphoma (PCNSL) treatment to disease progression or death, assessed up to 2 years
Overall survival
OS will be assessed using Kaplan-Meier product limit estimates and compared between patients with obinutuzumab maintenance versus without maintenance using the log-rank test. Longitudinal data of neurocognitive function and QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: From the start date of first-line PCNSL treatment to death, assessed up to 2 years.
Neurocognitive function - Hopkins Verbal Learning Test-Revised
Will be measured by the Hopkins Verbal Learning Test-Revised. Test evaluates total recall, delayed recall, percent of retention, and recognition. Higher score means better outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: Up to 2 years
Neurocognitive function - Grooved Pegboard Test
Will be measured by the Grooved Pegboard Test. Scale 0 seconds to time of completion in minutes and seconds. Higher time to completion means worse outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: Up to 2 years
Neurocognitive function - Trail Making Test
Will be measured by the Trail Making Test. Scale Part A: 0 seconds to 100 seconds (time of greater than 100 seconds discontinues the test. Scale Part B: 0 seconds to 300 seconds (time of greater than 300 seconds discontinues the test. Number of errors recorded. Higher time to completion and greater number of errors means worse outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: Up to 2 years
Neurocognitive function - Brief Test of Attention
Will be measured by the Trail Making Test. Scale 0 to 20 points. Higher score mean better outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: Up to 2 years
Quality of life (QOL) - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item
Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Core 30-item (EORTC QLQ-C30) questionnaire. Scale 30 to 126 points. Higher score means worse outcome. Longitudinal data of QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.
Time frame: Up to 2 years
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