An Open-labeled, Randomized, Two-dose, Parallel Group Trial of Ofatumumab, a Fully Human Monoclonal Anti-CD20 Antibody, in Combination With Fludarabine and Cyclophosphamide, in Patients With Previously Untreated B-cell CLL
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Number of Participants (Par.) With Complete Remission (CR), Measured From Start of Treatment Until 3 Months After Last Infusion
研究概览
简要总结
To investigate the safety and efficacy of two dose regimes of ofatumumab in combination with chemotherapy in previously untreated patients with B-CLL
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
- •Patients with active B-CLL and with an indication for treatment
- •Age ≥ 18 years
- •Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out
排除标准
- •Any previous treatment for B-CLL or any other treatments that can be considered active against B-CLL
- •Glucocorticoid unless given in doses ≤ 10 mg /day for other indications than B-CLL (e.g. asthma)
- •Known transformation of B-CLL
- •Known CNS involvement of B-CLL
- •Past or current malignancy, except for:
- •Cervical carcinoma Stage 1B or less
- •Non-invasive basal cell and squamous cell skin carcinoma
- •Malignant melanoma with a complete response of a duration of > 10 years
- •Other cancer diagnoses with a complete response of a duration of > 5 years
- •Chronic or current infectious disease requiring systemic treatment
- •Clinically significant cardiac disease
- •Significant concurrent, uncontrolled medical condition
- •History of significant cerebrovascular disease
- •Known HIV positive
- •Positive serology for hepatitis B, unless due to vaccination
- •Leukapheresis, except as a safety measure before chemotherapy
- •ECOG Performance Status of 3 or 4
- •Patients who at the time of inclusion are not expected to be able to complete the ofatumumab-FC regimen
- •Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 1
- •Current participation in any other interventional clinical study
- •Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
- •Breast feeding women or women with a positive pregnancy test at Visit 1
- •Women of childbearing potential not willing to use adequate contraception for up to one year after last dose of ofatumumab. Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the USA the use of a double barrier method is also considered adequate.
研究组 & 干预措施
Active Comparator 1
Each patient will receive a total of 6 infusions with ofatumumab every 4 weeks in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 500mg
干预措施: Ofatumumab 500mg (Drug)
Active Comparator 1
Each patient will receive a total of 6 infusions with ofatumumab every 4 weeks in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 500mg
干预措施: Fludarabine (Drug)
Active Comparator 1
Each patient will receive a total of 6 infusions with ofatumumab every 4 weeks in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 500mg
干预措施: Cyclophosphamide (Drug)
Active Comparator 2
Each patient will receive a total of 6 monthly infusions with ofatumumab in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 1000mg
干预措施: Ofatumumab 1000mg (Drug)
Active Comparator 2
Each patient will receive a total of 6 monthly infusions with ofatumumab in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 1000mg
干预措施: Fludarabine (Drug)
Active Comparator 2
Each patient will receive a total of 6 monthly infusions with ofatumumab in combination with fludarabine and cyclophosphamide. The first infusion will be 300mg followed by 5 infusions of 1000mg
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Number of Participants (Par.) With Complete Remission (CR), Measured From Start of Treatment Until 3 Months After Last Infusion
时间窗: Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)
Par. were evaluated for response by an Independent Endpoint Review Committee (IRC) in accordance with the National Cancer Institute-sponsored Working Group (NCI-WG) 1996 guideline. Par. with Complete Remission (CR) were classified as "complete responders". As per NCI-WG, CR requires all of the following criteria for a period of \>=2 months: absence of lymphadenopathy (all lymph nodes \<1.0 centimeters), no hepatomegaly/splenomegaly, absence of constitutional symptoms, lymphocytes \<=4.0\*10\^9/liter (L), neutrophil leukocytes \>=1.5\*10\^9/L, platelets \>100\*10\^9/L, and hemoglobin \>11 grams/deciliter.
Number of Participants (Par.) Who Were Classified as Responders and Non-responders
时间窗: From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)
Par. were evaluated by an IRC in accordance with NCI-WG 1996 guideline. Responders: CR, Nodular Partial Remission (nPR, same as CR, but persistent bone marrow nodules), and Partial Remission (PR, \>=50% decrease in lymphocytes from pretreatment baseline (BL) value, \>=50% reduction in lymphadenopathy, \>=50% reduction of liver/spleen and neutrophils \>= 1.5\*10\^9/L or platelets \>100\*10\^9/L or hemoglobin \>11 g/dL (or 50% improvement over BL for neutrophils, platelets, hemoglobin); non-responders: Stable Disease (SD, did not achieve CR/PR, and no PD), Progressive Disease (PD), or Not Evaluable (NE).
次要结局
- Duration of Response(From time of initial response to disease progression or death, whichever came first, assessed over 2 years)
- Progression-Free Survival(From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years)
- Time to Next Anti-chronic Lymphocytic Leukemia (CLL) Therapy or Death(From time of randomization to first administration of next anti-CLL therapy other than ofatumumab or death, assessed over 5 years)
- Median Percent Change in Tumor Size From Baseline (Visit 2, Wk 0) at Visits 9, 21, 25, 29, 33, 34, 35, and 37(Baseline Visit 2 (Week [Wk] 0); Visits 9 (Wk 4), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI), 35 (M 6 after start of LI), 36 (M 9 after start of LI), and 37 (M 12 after start of L)
- Median Percent Change in CD5+CD19+ and CD5+CD20+ Cells in Peripheral Blood From Onset of Course 3 Throughout Follow-up (FU) Compared to Screening(Baseline Visit 2 (Week [Wk] 0); Visits 15 (Wk 8), 21 (Wk 12), 25 (Wk 16), 29 (Wk 20), 33 (Month [M] 1 after start of last infusion [LI]), 34 (M 3 after start of LI))
- Number of Participants Who Experienced Any Adverse Event From First Treatment (Visit 2) to Visit 43 (Month 60)(From first treatment (Visit 2) up to Visit 43 (Month 60))
- Number of Participants With Positive Human Anti-human Anti Bodies (HAHA) at Visits 1, 21, 35, and 39(Visits 1 (Screening, Visit -2), 21 (Week 12), 35 (Month 6), and 39 (Month 18))
- Vss After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)(Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose))
- Number of Participants Who Reported Myelosuppression (Anemia, Leukopenia, Neutropenia, and Thrombocytopenia)(From first treatment (Visit 2) up to Visit 43 (Month 60))
- Percent Change From Screening (Visit 1) in Complement (CH50) Levels at Visit 9 (Week 4)(Visit 1 (Week -2) and Visit 9 (Week 4))
- Number of Participants Classified as Responders Having CR Who Tested Negative for Minimal Residual Disease (MRD)(From start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to course 6 or Week 32))
- Ctrough and Cmax at the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)(Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose))
- AUC(0-inf) and AUC(0-672) After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)(Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose))
- t1/2 After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)(Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose))
- CL After the First Infusion (Visit 2, Week 0) and Sixth Infusion (Visit 29, Week 20)(Visit 2 (Week 0; up to 4 weeks after dose) and Visit 29 (Week 20; up to 9 months after dose))
- Number of Participants With Progression or Death(From time of randomization to first documented evidence of disease progression or death due to any cause, whichever came first, assessed over 2 years)