An Open Label, Multicenter Study Investigating the Safety and Efficacy of Ofatumumab Therapy Versus Physicians' Choice in Patients With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukaemia (CLL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC)
研究概览
简要总结
The purpose of this study was to confirm the clinical benefit observed in the pivotal registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP) required that a randomized study be conducted in CLL patients with bulky fludarabine-refractory disease as a specific obligation for grant of conditional approval for ARZERRA™ in the European Union (EU). This study compared ofatumumab with the physicians' choice of therapy.
详细描述
Patients with CLL that is refractory to fludarabine have few treatment options and a poor prognosis. There is a continued need for new therapies for these CLL patients, as demonstrated by the limited responses and substantial toxicities with existing therapies. This is supported by the lack of a consensus around standard of care treatment for CLL patients with bulky fludarabine-refractory disease. The objective of this study was to confirm the response rate and disease control in the refractory setting through a controlled trial comparing ofatumumab with the physicians' choice of therapy in fludarabine-refractory, bulky lymphadenopathy patients. After 24 weeks of treatment with ofatumumab, patients were further randomized to either extended ofatumumab treatment or observation. Patients on the physicians' choice arm had the option of receiving ofatumumab if they experience progressive disease.
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
- •Adults with documented diagnosis of active CLL requiring treatment
- •Bulky lymphadenopathy, defined as at least 1 lymph node >5 cm
- •Must be refractory to fludarabine treatment
- •Age 18 yrs or older
- •At least 2 prior therapies for CLL
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Signed written informed consent
排除标准
- •Prior allogeneic stem cell transplant at any time, or autologous stem cell transplant within 6 months
- •Treatment with any unapproved drug substance or experimental therapy within 4 weeks, or currently participating in another interventional clinical study
- •CLL transformation, prolymphocytic leukemia, or central nervous system (CNS) involvement of CLL
- •Active autoimmune hemolytic anemia (AIHA) requiring treatment except if associated with progressive disease requiring anti-CLL treatment
- •Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
- •Human immunodeficiency virus (HIV) positive
- •Significant concurrent, uncontrolled medical condition
- •Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumor was successfully treated with curative intent at least 2 years prior to trial entry
- •Non-protocol corticosteroid usage except a maintenance dose corresponding to less than or equal to 10 mg prednisone
- •Abnormal lab values: Creatinine > 2.0 times upper normal limit (unless normal creatinine clearance), or total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of CLL or due to Gilbert's syndrome), or alanine transaminase (ALT) > 2.5 times upper normal limit (unless due to liver involvement of CLL)
- •Known or suspected hypersensitivity to ofatumumab
- •Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception
研究组 & 干预措施
Ofatumumab
Biological
干预措施: Ofatumumab (Drug)
Physicians' Choice
Physicians' choice of treatment
干预措施: Physicians' Choice (Drug)
结局指标
主要结局
Progression-free Survival (PFS) as Assessed by Independent Review Committee (IRC)
时间窗: From the randomization date up to 60 months post the randomization date.
PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, \>=50% increase in liver or spleen size, \>=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.
次要结局
- Overall Response Rate (ORR) as Assessed by the Investigator(From the randomization date up to 60 months post the randomization date.)
- Time to Progression as Assessed by IRC(From the randomization date up to 60 months post the randomization date.)
- Time to Next Anti-cancer Therapy by Investigator(From the randomization date up to 60 months post the randomization date.)
- Number of Participants Who Were Positive or Negative for Human Anti-Human Antibodies (HAHA) Post-OFA Therapy(From the randomization date up to 60 months post the randomization date.)
- Mean Health Change Questionnaire (HCQ) Score(From the randomization date up to 60 months post the randomization date.)
- Mean Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM Over Time(Screening and every 3 months during treatment, every 6 months after last treatment until PD or until 42 Month Follow-up Visit)
- Progression-free Survival (PFS) as Assessed by Investigator(From the randomization date up to 60 months post the randomization date.)
- Overall Survival(From the randomization date up to 60 months post the randomization date.)
- Changes From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)(From the randomization date up to 60 months post the randomization date.)
- Duration of Response as Assessed by the IRC(From the randomization date up to 60 months post the randomization date.)
- Number of Participants With Any Adverse Event (AE), Any Serious Adverse Event (SAE), Any Fatal Serious Adverse Event (FSAE), or Deaths(From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy)
- Overall Response Rate (ORR) as Assessed by the IRC(From the randomization date up to 60 months post the randomization date.)
- Time to Response as Assessed by the IRC(From the randomization date up to 60 months post the randomization date.)
- Number of Participants With Any Adverse Event (AE) of Special Interest(From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy)