A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacodynamics of GS-9973 in Combination With Idelalisib in Subjects With Relapsed or Refractory Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 66
- 试验地点
- 13
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This study will evaluate the efficacy of the combination entospletinib and idelalisib in participants with relapsed or refractory hematologic malignancies. Participants will be enrolled who have one of the following hematological tumor types: chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or indolent non-Hodgkin lymphomas (iNHL; including follicular lymphoma (FL) and lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia [LPL/WM], small lymphocytic lymphoma [SLL], or marginal zone lymphoma [MZL]).
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 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
- •Diagnosis of B-cell indolent non-Hodgkin lymphoma (iNHL),diffuse large B-cell lymphoma (DLBCL),mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) as documented by medical records and with histology based on criteria established by the World Health Organization
- •For institutions that have Phase 3 or Phase 4 protocols studying idelalisib (Zydelig®; GS-1101); individuals with malignancies being studied in these protocols must have failed screening and be registered as a screen failure in the respective idelalisib protocol
- •Prior treatment for lymphoid malignancy
- •Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
- •Discontinuation of all therapy for the treatment of cancer ≥ 3 weeks before the start of study drug
- •All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study drug
- •Karnofsky performance status of ≥ 60
- •Life expectancy of at least 3 months
排除标准
- •Known histological transformation from iNHL or CLL to an aggressive form of NHL (ie, Richter transformation)
- •Known active central nervous system or leptomeningeal lymphoma
- •Presence of known intermediate- or high-grade myelodysplastic syndrome
- •Current therapy with agents that reduce gastric acidity, including but not limited to antacids, H2 inhibitors, and proton pump inhibitors
- •Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study drug
- •Ongoing liver injury
- •Ongoing or recent hepatic encephalopathy
- •Ongoing drug-induced pneumonitis
- •Ongoing inflammatory bowel disease
- •Ongoing alcohol or drug addiction
- •Pregnancy or breastfeeding
- •History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
- •Ongoing immunosuppressive therapy
- •Concurrent participation in an investigational drug trial with therapeutic intent
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Entospletinib + idelalisib
Entospletinib plus idelalisib at one of 4 dose combinations (400 mg/100 mg; 600 mg/100 mg; 800 mg/100 mg; 800 mg/150 mg).
After discontinuation of entospletinib+idelalisib combination therapy, and following a washout period, participants may continue to receive entospletinib 400 mg monotherapy.
干预措施: Entospletinib (Drug)
Entospletinib + idelalisib
Entospletinib plus idelalisib at one of 4 dose combinations (400 mg/100 mg; 600 mg/100 mg; 800 mg/100 mg; 800 mg/150 mg).
After discontinuation of entospletinib+idelalisib combination therapy, and following a washout period, participants may continue to receive entospletinib 400 mg monotherapy.
干预措施: Idelalisib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Start of treatment to end of treatment (Up to 18 months)
ORR assessed by the Independent Review Committee (IRC), was based on the International Working Group Revised Response Criteria (Cheson, 2012) and investigator's response, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) (or very good partial response \[VGPR\] or minor response \[MR\] for participants with LPL/WM). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but \< 50% decrease from baseline in serum monoclonal immunoglobulin M (IgM) concentration by serum protein electrophoresis (SPEP) respectively.
次要结局
- Duration of Response (DOR)(Start of treatment to end of treatment (Up to 18 months))
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events(First dose date up to the last dose date plus 30 days (maximum duration: 19 months))
- Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities(First dose date up to the last dose date plus 30 days (maximum: 18 months))
- Maximum Tolerated Dose Level(First dose (entospelinib + idelalisib) date up to 6 months)
- Progression-free Survival (PFS)(Start of treatment to end of treatment (Up to 18 months))
- Time to Response (TTR)(Start of treatment to end of treatment (Up to 18 months))