A Phase 2 Study to Assess the Efficacy and Safety of Idelalisib in Subjects With Indolent B-Cell Non-Hodgkin Lymphomas Refractory to Rituximab and Alkylating Agents
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 125
- 试验地点
- 41
- 主要终点
- Overall Response Rate
研究概览
简要总结
The primary objective will be to assess the overall response rate and to evaluate the efficacy and safety of idelalisib (IDELA; GS-1101) in participants with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy.
Eligible participants will initiate oral therapy with idelalisib at a starting dose of 150 mg taken twice per day. Treatment with idelalisib can continue in compliant participants as long as the study is still ongoing and the participants appear to be benefiting from treatment with acceptable safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Karnofsky performance status of ≥ 60 (Eastern Cooperative Oncology Group [ECOG] performance score of 0, 1, or 2)
- •Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following:
- •Follicular lymphoma (FL)
- •Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10^9/L at the time of diagnosis and on baseline laboratory assessment performed within 4 weeks prior to the start of study drug administration
- •Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM)
- •Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal)
- •Prior treatment with ≥ 2 prior chemotherapy-based or immunotherapy-based regimens for iNHL
- •Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
- •Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL
- •Lymphoma that is refractory to rituximab and to an alkylating agent
- •Discontinuation of all other therapies for treatment of iNHL ≥ 3 weeks before Visit 2
- •For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods
- •Willingness and ability to provide written informed consent and to comply with the protocol requirements
排除标准
- •Central nervous system or leptomeningeal lymphoma
- •Known histological transformation from iNHL to diffuse large B-cell lymphoma
- •History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years
- •Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment
- •Pregnancy or breastfeeding
- •Ongoing alcohol or drug addiction
- •Known history of drug-induced liver injury, chronic active hepatitis B infection, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension
- •History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
- •Ongoing immunosuppressive therapy, including systemic corticosteroids. Participant may be using topical or inhaled corticosteroids.
- •Prior therapy with idelalisib
- •Exposure to another investigational drug within 3 weeks prior to start of study treatment
- •Concurrent participation in another therapeutic treatment trial
- •Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the participant, alter the absorption, distribution, metabolism or excretion of the study drug, or impair the assessment of study results
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Idelalisib
Treatment with idelalisib will be continued until tumor progression or development of unacceptable toxicity.
干预措施: Idelalisib (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: Start of Treatment to End of Treatment (up to 81 months)
Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) or partial response (PR; or minor response \[MR\] for participants with WM) as assessed by the study independent review committee (IRC). 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. For WM only, response was defined as a reduction in immunoglobulin M (IgM) of ≥ 50% decrease for PR, and ≥ 25% decrease for MR; no increase from baseline in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions or signs and symptoms of active disease (Owen, 2013)
次要结局
- Duration of Response(Start of Treatment to End of Treatment (up to 81 months))
- Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms(Start of Treatment to End of Treatment (up to 81 months) plus 30 days)
- Time to Response(Start of Treatment to End of Treatment (up to 81 months))
- Change in Karnofsky Performance Status(Baseline to End of Treatment (up to 81 months))
- Lymph Node Response Rate(Start of Treatment to End of Treatment (up to 81 months))
- Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS)(Baseline to End of Treatment (up to 81 months))
- PK Parameter: AUClast(Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29)
- Overall Survival(Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years))
- Study Drug Exposure(Start of Treatment to End of Treatment (up to 81 months))
- Idelalisib Plasma Concentration(Predose and at 1.5 hours (± 5 minutes) postdose on Day 29)
- PK Parameter: Cmax(Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29)
- Progression-Free Survival(Start of Treatment to End of Treatment (up to 81 months))
- PK Parameter: Tmax(Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29)
- Changes in Plasma Concentrations of Disease-Associated Chemokines and Cytokines(Enrollment to End of Treatment (up to 81 months))