Phase 3, Randomized Study to Assess the Efficacy and Safety of Ublituximab in Combination With TGR-1202 (Umbralisib) Compared to Obinutuzumab in Combination With Chlorambucil in Patients With Chronic Lymphocytic Leukemia (CLL)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 603
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria
研究概览
简要总结
This study evaluates the combination of ublituximab, a novel monoclonal antibody, and TGR-1202, a novel PI3K delta inhibitor compared to obinutuzumab and chlorambucil, and compared to ublituximab or TGR-1202 alone in Chronic Lymphocytic Leukemia (CLL) participants.
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
- •Treatment naïve or previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment
- •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 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)
- •Prior therapy with obinutuzumab and/or chlorambucil or a PI3K delta inhibitor
研究组 & 干预措施
Arm A: Ublituximab + Umbralisib
Participants received ublituximab, 150 milligrams (mg), intravenously (IV), on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 cycles thereafter, along with umbralisib, 800 mg, orally, once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
干预措施: Ublituximab (Biological)
Arm A: Ublituximab + Umbralisib
Participants received ublituximab, 150 milligrams (mg), intravenously (IV), on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 cycles thereafter, along with umbralisib, 800 mg, orally, once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
干预措施: TGR-1202 (Drug)
Arm B: Obinutuzumab + Chlorambucil
Participants received Obinutuzumab 100 mg, IV on Day 1, 900 mg on Day 2, followed by 1000 mg on Days 8 and 15 of cycle 1 (cycle length = 28 days), Day 1 of Cycle 2-6 along with Chlorambucil 0.5 milligram per kilogram (mg/kg) tablet orally on Days 1 and 15 once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
干预措施: Obinutuzumab (Biological)
Arm B: Obinutuzumab + Chlorambucil
Participants received Obinutuzumab 100 mg, IV on Day 1, 900 mg on Day 2, followed by 1000 mg on Days 8 and 15 of cycle 1 (cycle length = 28 days), Day 1 of Cycle 2-6 along with Chlorambucil 0.5 milligram per kilogram (mg/kg) tablet orally on Days 1 and 15 once daily during each cycle until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
干预措施: Chlorambucil (Drug)
Arm C: Ublituximab
Participants received ublituximab, 150 mg, IV, on Day 1, 750 mg on Day 2, followed by 900 mg on Days 8 and 15 of Cycle 1 (cycle length=28 days), Day 1 of Cycles 2-6, and once every 3 cycles thereafter, until disease progression, lack of tolerability, or until the treatment is commercially available or up to 87 months.
干预措施: Ublituximab (Biological)
Arm D: Umbralisib
Participants received umbralisib, 800 mg tablets, orally, once daily during each cycle (cycle length= 28 days) until removal from study or up to 87 months.
干预措施: TGR-1202 (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) Per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria
时间窗: From enrolment to the earlier of the first documentation of definitive disease progression (PD) or death (Up to 87 months)
PFS was defined as the interval from enrollment to the earlier of the first documentation of definitive disease progression (PD) or death from any cause. PD was appearance of new nodes \>1.5 centimetres (cm) in the longest diameter (LD) and \>1.0 in longest perpendicular diameter (LPD), new or recurrent hepatomegaly or splenomegaly, new or reappearance of an unequivocal extra-nodal lesion, ≥50% increase from the nadir in the sum of products of diameters (SPD) of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, \>50% decrease from the highest on-study platelet count, \>20 grams per Liter (g/L) decrease from the highest on-study hemoglobin (Hgb).
次要结局
- Overall Response Rate (ORR) Per iwCLL Criteria(Up to 87 months)
- Minimal Residual Disease (MRD) Negativity Rate(From Cycle 6 until Cycle 15 (cycle length=28 days) up to approximately 81.5 months)
- Complete Response (CR) Rate(Up to 87 months)
- Duration of Response (DOR)(From first documentation of response to study treatment till disease progression/death (up to approximately 87 months))
- Number of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)(From first dose of study treatment up to end of study (up to approximately 87 months))