A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 18
- 主要终点
- Progression-Free Survival
研究概览
简要总结
The primary objective of this study is to evaluate the effects of idelalisib with obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).
An increased rate of deaths and serious adverse events (SAEs) among participants with front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated those studies in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA). All front-line studies of idelalisib, including this study, were also terminated.
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
- •Not a candidate for fludarabine therapy based on either:
- •creatinine clearance < 70 mL/min, or
- •Cumulative Illness Rating Scale score > 6, by assessment of the investigator
- •Diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
- •No prior therapy for CLL other than corticosteroids for disease complications.
- •CLL that warrants treatment
- •Presence of measurable lymphadenopathy
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
排除标准
- •Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
- •Known presence of myelodysplastic syndrome
- •Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization
- •Ongoing liver injury
- •Ongoing drug-induced pneumonitis
- •Ongoing inflammatory bowel disease
- •History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
- •Ongoing immunosuppressive therapy other than corticosteroids
- •Concurrent participation in another therapeutic clinical trial
- •Undergone major surgery within 30 days prior to randomization
- •Known hypersensitivity or intolerance to any of the active substances or excipients in the formulations for idelalisib, obinutuzumab, or chlorambucil
- •History of non-infectious pneumonitis
- •Received last dose of study drug on another therapeutic clinical trial within 30 days prior to randomization
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Safety Run-In: Idelalisib+obinutuzumab
Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Following 4 weeks of treatment, safety data will be reviewed by an independent data monitoring committee (DMC). If acceptable tolerability is observed, the randomized portion of the study will begin.
干预措施: Idelalisib (Drug)
Safety Run-In: Idelalisib+obinutuzumab
Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Following 4 weeks of treatment, safety data will be reviewed by an independent data monitoring committee (DMC). If acceptable tolerability is observed, the randomized portion of the study will begin.
干预措施: Obinutuzumab (Drug)
Randomized: Idelalisib+obinutuzumab
Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.
干预措施: Idelalisib (Drug)
Randomized: Idelalisib+obinutuzumab
Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.
干预措施: Obinutuzumab (Drug)
Randomized: Obinutuzumab+chlorambucil
Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.
干预措施: Chlorambucil (Drug)
Randomized: Obinutuzumab+chlorambucil
Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Progression-Free Survival
时间窗: Up to 11 months
Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone. PFS was to be assessed by an independent review committee (IRC).
次要结局
- Complete Response Rate(Up to 11 months)
- Overall Survival(Up to 11 months)
- Overall Response Rate(Up to 11 months)
- Nodal Response Rate(Up to 11 months)
- Minimal Residual Disease Negativity Rate at Week 36(Up to 11 months)