Portland, Oregon 97239


Purpose:

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). Monoclonal antibodies, such as obinutuzumab, may kill cancer cells that are left after chemotherapy.


Study summary:

PRIMARY OBJECTIVES: I. To determine the effect of maintenance obinutuzumab on duration of complete response (CR) in patients with cluster of differentiation (CD)20+ B-cell primary central nervous system lymphoma (PCNSL) who attain CR to first-line treatment with high-dose methotrexate-based chemotherapy. SECONDARY OBJECTIVES: I. To evaluate overall survival after CR (overall survival [OS]-CR). II. To evaluate neurocognitive function, quality of life, and neuroimaging as indicators of neurotoxicity. III. Progression-free survival (PFS) and overall survival 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 course, and on day 1 for the subsequent courses. Courses 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 3 years. After completion of study treatment, patients are followed up every 3 months for 1 year.


Criteria:

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 90 days of completion of first-line treatment regimen; must have achieved complete response (CR/unconfirmed complete response [CRu]) to first-line treatment - Brain magnetic resonance imaging (MRI) documenting CR 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) - Creatinine clearance > 30 mL/min (calculated according to institutional standards or using Cockcroft-Gault formula) - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 5 x ULN - Platelet >= 75,000 cells/mm^3 - Hemoglobin > 9 g/dL - Absolute neutrophil count > 1.5 x 10^9 cells/mm^3 - 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 >= 12 months after the last dose of obinutuzumab for women, and 3 months 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) - Positive hepatitis serology: - 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 - 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 - 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 - Vaccination with a live vaccine a minimum of 4 weeks prior to study enrollment


NCT ID:

NCT02498951


Primary Contact:

Principal Investigator
Edward Neuwelt
OHSU Knight Cancer Institute


Backup Contact:

N/A


Location Contact:

Portland, Oregon 97239
United States

Edward A. Neuwelt
Phone: 503-494-5626
Email: neuwelte@ohsu.edu

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 21, 2017

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