A Multicenter Phase II Study of Ofatumumab and Bortezomib (OB) in Previously Untreated Patients With Waldenstrom Macroglobulinemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Overall Response Rate (CR + PR + MR) of Ofatumumab in Combination With Bortezomib
研究概览
简要总结
This phase II trial studies how well giving ofatumumab together with bortezomib works in treating patients with previously untreated Waldenstrom macroglobulinemia. Monoclonal antibodies, such as ofatumumab and bortezomib, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving ofatumumab together with bortezomib may be a better way to block cancer growth
详细描述
PRIMARY OBJECTIVES:
I. Determine overall response rate (complete response [CR] + partial response [PR] + minor response [MR]) of ofatumumab in combination with bortezomib.
SECONDARY OBJECTIVES:
I. Determine complete remission (CR) rate, near (n)CR rate, very good partial response (VGPR) rate and PR rate per new criteria.
II. Determine 5 year progression free survival (PFS). III. Determine time to progression and duration of response of ofatumumab in conjunction with bortezomib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Diagnosis of Waldenstrom Macroglobulinemia and presence of cluster of differentiation (CD)20+ tumor cells as determined by immune-histochemistry or flow cytometric analysis in bone marrow or representative lymphoid tissue specimen; to be deemed eligible, patients must meet at least one of the following criteria:
- •Rising immunoglobulin (Ig)M
- •Hemoglobin =< 10 g/dL
- •Platelet count =< 100 x 10^9/L
- •Symptomatic or bulky lymphadenopathy or organomegaly
- •Systemic manifestations of Waldenstrom Macroglobulinemia (WM), such as hyperviscosity symptoms (patients with symptoms of hyperviscosity syndrome must be treated with plasmapheresis to control the syndrome prior to enrollment), neuropathy, amyloidosis, cryoglobulinemia, B-symptoms, or recurrent bleeding
- •Must have a measurable disease as defined by the monoclonal IgM level of 1 g/dL on serum protein electrophoresis (SPEP); if the level of IgM on SPEP is less than 1 g/dL in patients who meet any criteria in inclusion criteria 2, then the IgM level obtained from nephelometric measurement may be used to justify this criterion
- •Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2
- •Have a life expectancy of >= 3 months
- •Absolute neutrophil count >= 1.0 x 10^9/L unless the result of disease infiltration of bone marrow
- •Platelet count >= 50 x 10^9/L unless the result of disease infiltration of bone marrow
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x the institutional upper limit of normal (ULN)
- •Total bilirubin =< 3 mg/dL or 1.5 x institutional ULN, whichever is lower
- •Serum creatinine =< 3 mg/dL
- •Female patients are either post-menopausal or surgically sterilized otherwise they must agree to use acceptable contraceptive methods (e.g. double barrier) during treatment
- •Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to one of the following:
- •Practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug
- •Completely abstain from heterosexual intercourse
- •Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent prior to receiving any study related procedure
排除标准
- •Pregnant and nursing female patients
- •Prior anti-neoplastic therapy for WM; the use of plasmapheresis to manage the symptoms of hyperviscosity and other IgM paraprotein mediated symptoms is allowed and does not disqualify a patient from the study; if a patient undergoes plasmapheresis within 8 weeks of starting the study treatment then the IgM level prior to plasmapheresis should be used for response assessment; neoplastic use of glucocorticoids is prohibited during the screening and treatment period; patients with active hyperviscosity symptoms should not be enrolled in this study unless the symptoms resolve after plasmapheresis
- •Unwilling or unable to follow protocol requirements
- •Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug
- •Received an investigational agent within 30 days prior to enrollment
- •Known human immunodeficiency virus (HIV) positive
- •Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if HBsAg is negative and hepatitis B core antibody (HBcAb) is positive, regardless of hepatitis B surface antibody (HBsAb) status, a HB deoxyribonucleic acid test will be performed and if HB DNA is positive the patient will be excluded; if a patient is HBsAg negative, HBcAb positive, and HBsAb positive, indicating past but not active infection, the patient will be included on the study
- •Positive serology for hepatitis C (HC) defined as a positive test for Hep C by enzyme immunoassays (EIA), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result
- •Diagnosis of a malignant disorder other than WM within 3 years of the study enrollment with the exception of completely resected non-melanoma skin cancer and successfully treated in-situ cancer
- •Uncontrolled infection
- •Hypersensitivity to bortezomib, boron, or mannitol
- •Grade 2 or greater peripheral neuropathy; since WM is known to cause peripheral neuropathy (PN), if, in investigator's judgement, a patient has Grade 2 PN related to WM, then he/she can be enrolled onto the study; under no circumstances patient with greater than Grade 2 PN can be enrolled
- •Myocardial infarction within 6 months of enrollment; New York Heart Association (NYHA) Class III or more heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias; arrhythmias requiring active therapy other than chronic stable atrial fibrillation; if a patient has an implanted cardiac pacemaker and is otherwise well can be enrolled onto this study after demonstrating normal ejection fraction and clearance from a cardiologist; at the time of screening any electrocardiographic abnormality has to be documented as not medically relevant by the investigator before the patient proceeds to the enrollment phase
- •Any serious medical or psychiatric illness that may interfere with participation in the study
- •Patients with symptoms of hyperviscosity syndrome will not be enrolled on the study until they undergo plasmapheresis that results in resolution of symptoms and optimal control of the syndrome
研究组 & 干预措施
Treatment (monoclonal antibody therapy)
INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: ofatumumab (Biological)
Treatment (monoclonal antibody therapy)
INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Treatment (monoclonal antibody therapy)
INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Overall Response Rate (CR + PR + MR) of Ofatumumab in Combination With Bortezomib
时间窗: Every 28 days
Assessed using the Consensus Panel recommendations from the Third International Workshop on Waldenstrom Macroglobulinemia.
次要结局
- Frequency of PR(Every 28 days)
- Time to Progression(From start of treatment to disease progression, assessed up to 12 months)
- Progression-free Survival(From start of treatment to disease progression or death (regardless of the cause of death), whichever comes first, assessed up to 12 months)
- Frequency of Complete Remission (CR)(Every 28 days)
- Frequency of Near (n)CR(Every 28 days)
- Frequency of Very Good Partial Response (VGPR)(Every 28 days)
- Duration of Response(From the observation of a response to the time of disease progression, assessed up to 12 months)
- Frequency and Severity of Toxicity as Graded According to the Cancer Therapeutic Evaluation Program (CTEP) Common Toxicity Criteria (CTC) Version 4.0(Every 30 days for 2 months)