A Phase 3, Randomized, Study to Assess the Efficacy and Safety of Ublituximab in Combination With Ibrutinib Compared to Ibrutinib Alone, in Patients With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This study evaluates the effect of the addition of ublituximab, a novel monoclonal antibody, to ibrutinib compared to ibrutinib alone on antitumor activity, as measured by the overall response rate (ORR = CR [complete response] + PR [partial response]) in previously treated Chronic Lymphocytic Leukemia (CLL) participants with high-risk cytogenetic features. Half of the participants will receive ublituximab in combination with ibrutinib, while the other half will receive ibrutinib alone.
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
- •Previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
- •At least one high-risk cytogenetic feature defined by the presence of 17p deletion, 11q deletion and/or p53 mutation
- •Eastern Cooperative Oncology Group (ECOG) score of 0 to 2
排除标准
- •Any major surgery, chemotherapy or immunotherapy within the last 21 days
- •Evidence of hepatitis B virus, hepatitis C virus or known human immunodeficiency virus (HIV) infection
- •Autologous hematologic stem cell transplant within 3 months of study entry. Prior Allogeneic hematologic stem cell transplant is excluded
- •Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation)
- •Previous therapy with ibrutinib, or any drug that specifically inhibits Bruton's tyrosine kinase (BTK)
研究组 & 干预措施
Ibrutinib
Participants will receive ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 62 months.
干预措施: Ibrutinib (Drug)
Ublituximab + Ibrutinib
Participants will receive ublituximab intravenous (IV) infusion, up to 150 milligrams (mg) once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 62 months along with ibrutinib 420 mg capsules, orally, once daily (QD) in each 28-day cycle for up to 62 months.
干预措施: Ublituximab (Drug)
Ublituximab + Ibrutinib
Participants will receive ublituximab intravenous (IV) infusion, up to 150 milligrams (mg) once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 62 months along with ibrutinib 420 mg capsules, orally, once daily (QD) in each 28-day cycle for up to 62 months.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 62 months
ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: No evidence of new disease; Absolute lymphocyte count(ALC)\<4x10\^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters(cm) in longest diameter(LD); Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; Absolute neutrophil count(ANC)\>1.5x10\^9/L,platelets≥100x10\^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR criteria: No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC\<4x10\^9/L or \>=50% decrease from baseline in sum of products(SPD) of target nodal lesions; splenomegaly; hepatomegaly;\>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; response in any 1:ANC\>1.5x10\^9/L,platelets\>100x10\^9/L,Hgb\>110g/L or \>=50% increase over baseline in any of these.
次要结局
- Minimum Residual Disease (MRD) Negativity Rate(Up to 62 months)
- Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)(From the first dose up to 30 days after the last dose of study drug (up to 57.3 months))
- Complete Response (CR) Rate(Up to 62 months)
- Progression-Free Survival (PFS)(From the randomization until the first documentation of PD or death whichever occurs first or up to 62 months)
- Duration of Response (DOR)(From the first dose of study drug until the first documentation of PD or death whichever occurs first or up to 62 months)
- Time to Response (TTR)(From the randomization up to 62 months)