A Phase I Study of Ipilimumab in Combination With Rituximab in Patients With Relapsed/Refractory CD20+ B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 14
- 主要终点
- Incidence of toxicities according to the Common Terminology Criteria for Adverse Events version 4
研究概览
简要总结
This partially randomized phase I trial studies the side effects and best dose of ipilimumab when given together with rituximab in treating patients with B-cell lymphoma that has returned or has not responded to treatment. Monoclonal antibodies, such as ipilimumab and rituximab, may interfere with the ability of cancer cells to grow and spread.
详细描述
PRIMARY OBJECTIVES:
I. To determine a recommended phase II dose for ipilimumab in combination with rituximab.
SECONDARY OBJECTIVES:
I. To obtain preliminary information on the effect of adding ipilimumab to rituximab in regard to: immune response; clinical anti-tumor response/overall remission rate (ORR) (complete remission + partial remission); progression free survival (PFS).
OUTLINE: This is a dose-escalation study of ipilimumab followed by a randomized study.
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
- None
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
- •Previously treated, histologically confirmed cluster of differentiation (CD)20+ B cell lymphoma; bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies or extra nodal biopsies; fine needle aspirates are not acceptable
- •All patients must be informed of the investigative nature of the clinical trial and give written informed consent in accordance with institutional and federal guidelines
- •Able to adhere to the study visit schedule and other protocol requirements
- •Karnofsky >= 70%
- •Life expectancy expected to be greater than 3 months
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count >= 1,000/mcL
- •Platelets >= 50,000/mcL
- •Total bilirubin =< 2.0 x institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- •Serum creatinine =< 2.0 x upper limit of normal OR calculated creatinine clearance >= 30 ml/min/1.73 M^2 by the modified Cockcroft and Gault formula OR creatinine clearance >= 30 mL/min obtained from a 24-hour urine collection
- •At least one measurable lesion according to international workshop lymphoma response criteria; there must be measurable lymphadenopathy to follow with serial exam and/or imaging
- •All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
- •Patients must have evidence of progression of disease during or after last treatment
- •Submission of original biopsy for review and verification by participating center hematopathologist
- •Disease free of prior malignancies for >= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients with a history of prior treatment with ipilimumab
- •Patients with a history of prior treatment with an anti-programmed cell death (PD) 1 antibody, CD137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded unless 5 half-lives of the agent (minimum of 8 weeks) have intervened since the therapy; patients who have received prior vaccine therapy are eligible
- •Patients who are receiving any other investigational agents
- •Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis)
- •Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte antigen 4 (CTLA 4) antibody
- •Patients with known uncontrolled brain metastases are excluded; however, patients with stable brain disease (off corticosteroids) at least 2 weeks after completion of appropriate therapy for their brain metastases are eligible
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab
- •Patients on systemic corticosteroids (except for patients on stable doses of hormone replacement therapy such as hydrocortisone), or other immunosuppressants (e.g., infliximab, mycophenolate mofetil) are excluded
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections are excluded
- •Pregnant women are excluded from this study
- •HIV-positive patients on combination antiretroviral therapy are ineligible
- •Rituximab within six weeks
研究组 & 干预措施
Arm A (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Rituximab (Biological)
Arm B (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Ipilimumab (Biological)
Arm B (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Rituximab (Biological)
Arm A (ipilimumab and rituximab)
Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Ipilimumab (Biological)
结局指标
主要结局
Incidence of toxicities according to the Common Terminology Criteria for Adverse Events version 4
时间窗: Up to 12 months
Tables will be created to summarize the toxicities and side effects by dose, course, organ and severity.
次要结局
- Immune response as measured by the frequency of activated T-cells, absolute lymphocyte count, antibody dependent cell-mediated cytotoxicity, and kinetics and magnitude of B-cell depletion(Up to 14 weeks)
- Clinical anti-tumor response (complete response and partial response as per international workshop lymphoma response criteria [Cheson 2007])(Up to 12 months)
- Progression-free survival(From when the patient started treatment to the time the patient is first recorded as having disease relapse/progression, or to the date of death if the patient dies due to causes other than disease progression, assessed up to 12 months)