Maintenance Obinutuzumab in Treating Patients with Central Nervous System Lymphoma Who Have Achieved a Complete or Partial Response
Brain & Spinal Cord Tumor
Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
IRB00011601 (primary)
NCI-2015-01014
ML29496
Summary
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.
Objectives
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.
Eligibility
- 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
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