A Phase III, Open Label, Randomized Trial of Ofatumumab Added to Fludarabine-Cyclophosphamide vs. Fludarabine-Cyclophosphamide Combination in Subjects With Relapsed Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 365
- 试验地点
- 3
- 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 fludarabine-cyclophosphamide in patients with relapsed Chronic Lymphocytic Leukemia (CLL).
详细描述
Fludarabine is currently approved for treatment of relapsed Chronic Lymphocytic Leukemia. Studies have shown that drugs in combination with fludarabine have shown more effectiveness than fludarabine alone. The addition of ofatumumab to fludarabine-cyclophosphamide combination offers potentially a more effective therapy, without additional toxicity.
The objective of this study was to determine the effect of ofatumumab added to fludarabine and cyclophosphamide in patients with Chronic Lymphocytic Leukemia who have responded previously to therapy but later develop progressive disease and require additional therapy.
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
- •confirmed and active CLL requiring treatment
- •at least one previous treatment for CLL and having achieved a complete or partial remission/response but after a period of 6 or more months, shows evidence of disease progression
- •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
- •diagnosis of refractory CLL (failure to achieve a complete or partial remission/response or disease progression within 6 months of last anti-CLL treatment
- •abnormal/inadequate blood values, liver and kidney function
- •certain heart problems, serious significant diseases, AIHA, other current cancers or within the last 5 years
- •active or chronic infections
- •use of drugs to suppress allergic or inflammatory responses (glucocorticoids)
- •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, Fludarabine, Cyclophosphamide
Ofatumumab Cycle 1-Day 1 300mg, Cycle 1-Day 8 1000mg, then Cycles 2-6 Day 1 1000mg every 28 days, Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles
干预措施: OFC Infusion (Drug)
Fludarabine, Cyclophosphamide
Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles
干预措施: FC infusion (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 up to 5 years after last dose of study drug
PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (progressive disease,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 enlargerd 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 (CLL).
次要结局
- Time to Response, as Assessed by the IRC(From randomization up to 5 years after last dose of study drug)
- Time to Progression, as Assessed by the IRC(From randomization up to 5 years after the last dose of study drug)
- Time to Next Therapy(From the start of study drug until the start of the next anti-CLL therapy (up to 5 years after the last dose of study drug))
- Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status(Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day1, follow up (FU) at 1Month (M) after study drug therapy, 3M, then every 3 month up to 5 year (up to 60 months))
- Number of Participants Who Were Negative for MRD Assessed by Investigator(From randomization up to 5 years after last dose of study drug)
- Changes in Patient Reported Outcome (PRO) Measures and Scores for European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)(Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.)
- Overall Survival (OS)(From randomization up to 5 years after last dose of study drug)
- Duration of Response (DOR), as Assessed by the IRC(From time of initial response to disease progression or death, whichever came first (up to 5 years after the last dose of study drug))
- Percentage of Participants With the Best OR, as Assessed by the Investigator(From randomization up to 5 years after last dose of study drug)
- Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time(Screening, Cycle1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and During at 1M after study drug therapy, 3M, then every 3 M up to 5 year (up to 60 months))
- Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC(From randomization up to 5 years after last dose of study drug)
- Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC(From randomization up to 5 years after last dose of study drug)
- Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points(From start of study drug until 60 days after the last dose of study medication)
- Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)(From first dose of study medication to 60 Days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE))
- Number of Participants With Autoimmune Hemolytic Anaemia (AIHA)(From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE))
- Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study(From randomization up to 5 years after last dose of study drug)
- Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+(Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three months up to 45 M during Follow-up Period)
- Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score(Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.)
- Mean of Health Change Questionnaire (HCQ)(Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.)
- Number of Participants With Drug Related Infections Reported as AEs and SAEs of Maximum Severity of Grade 3 or Higher(From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE))
- Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression Adverse Events(From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE))
- Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM(Baseline, 1M and 6M follow up)
- Change From Baseline in Cell Counts, CD5- CD19+(Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three month up to 45 M during Follow-up Period)
- Prognostic and Biological Markers Correlating With Clinical Response(From randomization up to 5 years after last dose of study drug)
- Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit(Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.)
- Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab(Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5,6)
- Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab(Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5)
- Time of Occurrence of Cmax (Tmax) of Ofatumumab(Cycle 1 Week 1, Cycle 1 Week 2, Cycle 4)