A Phase 3, Double-Blind Extension Study Evaluating the Efficacy and Safety of Two Different Dose Levels of Single-Agent Idelalisib (GS-1101) for Previously Treated Chronic Lymphocytic Leukemia A Companion Trial to Study GS-US-312-0116: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 161
- 试验地点
- 44
- 主要终点
- Safety: Percentage of Participants With Any Treatment-Emergent Adverse Events (TEAE), ≥ Grade 3 TEAE, Study Drug-Related TEAE, ≥ Grade 3 Study Drug-Related TEAE, Serious TEAE, Study Drug-Related Serious TEAE, and TEAE Leading to Study Drug Discontinuation
研究概览
简要总结
The primary objective of this extension study (GS-US-312-0117) that is a companion study to Study GS-US-312-0116 (NCT01539512), is to evaluate the effect of idelalisib on the onset, magnitude, and duration of tumor control. Randomization was done in study GS-US-312-0116, and carried forward to study GS-US-312-117.
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
- Double (Participant, Investigator)
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
- •Individuals in the primary Phase 3 study (Study GS-US-312-0116) who are compliant
- •Tolerating primary study therapy
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
排除标准
- 未提供
研究组 & 干预措施
High-dose Idelalisib
Participants will receive idelalisib 300 mg twice daily (600 mg per day).
干预措施: Idelalisib (Drug)
Standard-dose Idelalisib
Participants will receive idelalisib 150 mg twice daily (300 mg per day)
干预措施: Idelalisib (Drug)
结局指标
主要结局
Safety: Percentage of Participants With Any Treatment-Emergent Adverse Events (TEAE), ≥ Grade 3 TEAE, Study Drug-Related TEAE, ≥ Grade 3 Study Drug-Related TEAE, Serious TEAE, Study Drug-Related Serious TEAE, and TEAE Leading to Study Drug Discontinuation
时间窗: First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months) plus 4 weeks
The TEAEs were defined as events in a given study period that met one of the following criteria: * Events with onset dates on or after the start of treatment and up to 30 days after the permanent discontinuation of the study treatment. * The continuing adverse events (AEs) diagnosed prior to the start of treatment and worsened in severity grade, or non-serious AEs at baseline which became serious, or AEs resulting in treatment discontinuation after the start of treatment. The severity of AEs was graded by the investigator according to the common terminology criteria for adverse events (CTCAE), Version 4.03, whenever possible. The relationship of an AE to study drug (idelalisib) was assessed using clinical judgment by the investigator, describing the event as either unrelated or related. Events for which the investigator did not record relationship to study drug were considered related to study drug.
Progression-Free Survival (PFS)
时间窗: GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months)
PFS was defined as the interval from the start of study therapy to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is chronic lymphocytic leukemia (CLL) progression based on standard criteria other than lymphocytosis alone. PFS was analyzed using Kaplan-Meier (KM) estimates.
次要结局
- Duration of Response (DOR)(From first documentation of CR or PR to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Complete Response (CR) Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Hepatomegaly Response Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Plasma Trough (Predose) and Peak (1.5 Hours Postdose) Concentrations of Idelalisib(Weeks 4, 12, and 24)
- Overall Response Rate (ORR)(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Lymph Node Response Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Time to Response (TTR)(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Splenomegaly Response Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Best Percent Change in Lymph Node Area(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Absolute Lymphocyte Count (ALC) Response Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Study Drug Compliance as Assessed by the Percentage of Participants Adhering to Treatment(First IDL dose date in study GS-US-312-0116 or GS-US-312-0117 to last IDL dose date in study GS-US-312-0117 (maximum: 67.3 months))
- Platelet Response Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Best Change From Baseline in Karnofsky Performance Status (KPS)(Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 190)
- Changes From Baseline in Phosphatidylinositol 3-kinase (PI3Kδ)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway Activation as a Measure of PI3Kδ Pathway Activity(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Hemoglobin Response Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Neutrophil Response Rate(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Best Change From Baseline in Health-Related Quality of Life (HRQL) Domain and Symptom Scores Based on the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) Questionnaire(Study GS-US-312-0116 or GS-US-312-0117 Baseline up to Week 184)
- Overall Survival(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Overall Change From Baseline in the Plasma Concentrations of Disease-Associated Chemokines and Cytokines(GS-US-312-0116 Baseline to end of study GS-US-312-0117 (maximum: up to 67.6 months))
- Change in Health Status as Assessed Using the EuroQoL Five-Dimension (EQ-5D) Utility Measure(Study GS-US-312-0116 or GS-US-312-0117 Baseline; Weeks 24 and 48)