Maintenance Obinutuzumab for Primary Central Nervous System Lymphoma Complete or Partial Responders
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 7
- 主要终点
- Partial response (PR) or complete response (CR) duration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Single
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 at the time of randomization; 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 before randomization
- •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 before date of randomization
- •Creatinine clearance > 30 mL/min (calculated according to institutional standards or using Cockcroft-Gault formula), ≤ 7 days before date of randomization
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 5 x ULN, ≤7 days 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 of randomization
- •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
排除标准
- •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 randomization
- •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 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 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 randomization
研究组 & 干预措施
Arm I (obinutuzumab
Patients receive obinutuzumab IV on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles, 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.
干预措施: Cognitive Assessment (Procedure)
Arm I (obinutuzumab
Patients receive obinutuzumab IV on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles, 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.
干预措施: Obinutuzumab (Biological)
Arm I (obinutuzumab
Patients receive obinutuzumab IV on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles, 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.
干预措施: Quality of Life Assessment (Other)
Arm II (observation)
Patients undergo observation for a total of 2 years.
干预措施: Cognitive Assessment (Procedure)
Arm II (observation)
Patients undergo observation for a total of 2 years.
干预措施: Quality of Life Assessment (Other)
结局指标
主要结局
Partial response (PR) or complete response (CR) duration
时间窗: 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
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.
次要结局
- Overall survival (OS) after CR(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 - Brief Test of Attention(Up to 2 years)
- Neurocognitive function - Grooved Pegboard Test(Up to 2 years)
- Neurocognitive function - Wechsler Adult Intelligence Scale(Up to 2 years)
- Progression free survival (PFS)(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(From the start date of first-line PCNSL treatment to death, assessed up to 2 years.)
- Neurocognitive function - Trail Making Test(Up to 2 years)
- Quality of life (QOL) - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain Neoplasm 20-item(Up to 2 years)
- Neurocognitive function - Hopkins Verbal Learning Test-Revised(Up to 2 years)
- Quality of life (QOL) - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item(Up to 2 years)