A Phase III, Open Label, Randomized, Multicenter Trial of Ofatumumab Added to Chlorambucil Versus Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 447
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC)
研究概览
简要总结
The purpose of this study was to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.
详细描述
Chlorambucil, is currently approved for treatment of frontline chronic lymphocytic leukemia, especially, but not limited to the ailing and elderly patient population. Several other more aggressive treatment options are available (e.g. fludarabine), however they are not suitable for all CLL patients, especially the ailing and elderly, due to greater toxicity. Ofatumumab is effective with low toxicity. The addition of ofatumumab to chlorambucil offers potentially a more effective therapy, with limited toxicity. The objective of this study was to evaluate progression-free survival (PFS), overall response and overall survival in subjects with previously untreated CLL with ofatumumab added to chlorambucil versus chlorambucil.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •confirmed CLL diagnosis and active CLL requiring treatment
- •considered inappropriate for fludarabine-based therapy
- •not been treated for CLL before
- •fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours
- •age 18yrs or older
- •signed written informed consent
排除标准
- •prior CLL therapy
- •abnormal/inadequate blood values, liver, and kidney function
- •certain heart problems, active or chronic infections, serious significant diseases, active autoimmune hemolytic anemia (AIHA) requiring treatment, other current cancer or within last 5 years
- •CLL transformation
- •CLL central nervous system involvement
- •current participation in other clinical study
- •inability to comply with the protocol activities
- •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 + chlorambucil
ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles
干预措施: chlorambucil, tablets (Drug)
ofatumumab + chlorambucil
ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles
干预措施: ofatumumab (GSK1841157) infusion (Drug)
chlorambucil
chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles
干预措施: chlorambucil, tablets (Drug)
结局指标
主要结局
Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC)
时间窗: From randomization to the date of first documented disease progression or death due to any cause, whichever occured first, reported between day of first patient randomized up to about 49 months
PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (\>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment.
次要结局
- Number of Participants With the Best Overall Response (OR), as Assessed by the IRC(From randomization until the 259th PFS event occurred, up to about 49 months)
- Number of Participants Who Were Negative for Minimal Residual Disease (MRD)(From randomization until the 259th PFS event occurred (Median follow-up approximately 28.9 months))
- Overall Survival(From randomization up to about 111 months)
- Time to Response, as Assessed by the IRC(From randomization uo to about 27 months)
- Duration of Response (DOR), as Assessed by the IRC(From randomization up to about 43 months)
- Time to Progression, as Assessed by the IRC(From randomization up to about 49 months)
- Time to Next Therapy(From randomization up to about 49 months)
- Number of Participants With Improvement in ECOG Performance Status of 0 or 1(Baseline, Cycle 3 Day 1, 1 month Follow-up)
- Number of Participants With Improvement in Constitutional Symptoms (CS)(Baseline, Cycle 3 Day 1, and 1 month Follow-up)
- Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result(Baseline, Cycle 4 Day 1, 1 Month Follow-up, and 6 Month Follow-up)
- Cmax and Ctrough of Ofatumumab(Cycle 1 Day 1,Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, and Cycle 9 Day 1)
- Total Plasma Clearance (CL) of Ofatumumab(Cycle 4 Day 1)
- AUC(0-tau) of Ofatumumab(Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1)
- Volume of Distribution at Steady State (Vss) of Ofatumumab(Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1)
- Plasma Half Life (t1/2) of Ofatumumab(Cycle 4 Day 1)
- Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM)(Cycle 3 Day 1)
- Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM)(Cycle 3 Day 1)
- Change From Baseline in Health Related Quality of Life (HRQOL)(Baseline, Cycle 4 day 1, cycle 7 day 1, 1 month follow-up, 6 month follow-up, 12 month follow-up)
- Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)(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, up to approximately 111 months.)
- Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher(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, up to approximately 111 months.)
- Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study(From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 28.9 months))
- Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM(From start of treatment up to 30 days after last treatment)
- Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia)(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, up to approximately 111 months.)
- Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease(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, up to approximately 111 months.)