A Phase II Trial of Ofatumumab (CALGB IND #) in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 48
- 主要终点
- Overall Response Rate (Complete or Partial Response) by Month 12
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as ofatumumab, 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.
PURPOSE: This randomized phase II trial is studying ofatumumab to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.
详细描述
OBJECTIVES:
Primary
- To determine the response rate in patients with previously untreated CD20-positive bulky stage II, or stage III or IV follicular non-Hodgkin lymphoma (NHL) treated with a lower- or high-dose of ofatumumab.
Secondary
- To determine the progression-free survival (PFS) of patients treated with these regimens.
- To determine the toxicity profile of these regimens in these patients.
- To establish whether the therapeutic effect of single-agent ofatumumab is sufficiently promising to warrant evaluation in subsequent randomized, ofatumumab-based, biologic doublet trials.
- To evaluate the two ofatumumab doses by independent comparison of response, PFS, and toxicity to a historical control in previously untreated patients with follicular NHL.
- To prospectively validate the FLIPI2 prognostic index in low- and intermediate-risk patients and compare to low- and intermediate-risk stratified patients by standard FLIPI scoring to determine a more reliable indicator of response and PFS.
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed follicular non-Hodgkin lymphoma (NHL) meeting 1 of the following criteria:
- •Bulky (i.e., single mass ≥ 7cm in any uni-dimensional measurement) stage II disease
- •Stage III or IV disease
- •WHO grade 1, 2, or 3a disease
- •Bone marrow biopsies allowed provided they are submitted in conjunction with nodal biopsies
- •No fine-needle aspirates for diagnosis
- •Tumor tissue must express the CD20-positive antigen by flow cytometry or IHC
- •At least 1 site of measurable disease that is > 1 cm in diameter in ≥ 1 dimension present either on physical exam or imaging studies
- •Non-measurable disease alone not allowed, including the following:
- •Bone lesions (lesions if present should be noted)
- •Pleural/pericardial effusion
- •Lymphangitis cutis/pulmonis
- •Bone marrow (involvement by NHL should be noted)
- •Low- or intermediate-risk disease by the Follicular Lymphoma International Prognostic Index (FLIPI)
- •FLIPI score meeting 1 or 2 of the following risk factors:
- •Age > 60 years
- •Involvement of > 4 nodal sites
- •Stage III-IV disease
- •Hemoglobin < 12.0 g/dL
- •LDH normal
- •Risk determined by the following:
- •Low Risk: 0-1 of the above risk factors
- •Intermediate Risk: 2 risk factors
- •Poor Risk: ≥ 3 risk factors
- •No known CNS involvement
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-2
- •ANC ≥ 1,000/μL
- •Platelet count ≥ 75,000/μL
- •Creatinine clearance ≥ 30 mL/min
- •Bilirubin ≤ 2 times upper limit of normal (unless secondary to Gilbert syndrome or hepatic involvement of NHL)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- •Patients with HIV infection allowed provided the following criteria are met:
- •No evidence of coinfection with hepatitis B or C
- •CD4+ cell count ≥ 400/mm³
- •No evidence of resistant strains of HIV
- •HIV viral load < 10,000 copies HIV RNA/mL if not on anti-HIV therapy OR HIV viral load < 50 copies if on anti-HIV therapy
- •No history of AIDS-defining conditions
- •No evidence of active hepatitis B (HBV) or C (HCV) infection (i.e., no positive serology for anti-HBc or anti-HCV antibodies)
- •HBV seropositivity allowed (HBsAg+) provided they are closely monitored for evidence of active HBV infection by HBV DNA testing
- •After completing treatment, HBsAg + patients must be monitored by HBV DNA testing every 2 months for 6 months post-treatment, while continuing lamivudine (required)
- •PRIOR CONCURRENT THERAPY:
- •No prior chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy) for NHL
- •Prior involved-field radiation therapy allowed
- •More than 2 weeks since prior corticosteroids except for maintenance therapy for a non-malignant disease
- •No concurrent dexamethasone or other steroids as antiemetics
- •No live virus vaccination within 6 weeks prior to study entry
- 另有 1 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm II
Patients receive a lower dose of ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.
干预措施: ofatumumab (Biological)
Arm I
Patients receive high-dose ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.
干预措施: ofatumumab (Biological)
结局指标
主要结局
Overall Response Rate (Complete or Partial Response) by Month 12
时间窗: From baseline to month 12
The primary endpoint of this trial is overall response rate (OR=complete response (CR) or partial response (PR)) to 500 mg or 1000 mg dose of ofatumumab in previously untreated patients with CD20+ follicular NHL. The response outcome is defined as the best response during the 12 months of first-line and extended induction treatment. A CR is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is defined as at least a 50% decrease in the sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, with no increase observed in the size of other nodes, liver, or spleen and no new sites of disease should be observed. The ORR (percentage of patients) reported below by arm is the percentage of patients whose best response during the 12 months of treatment was CR or PR.
次要结局
- Median Progression-free Survival Time(From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years)