A Phase 2 Single Arm Study to Investigate the Safety and Clinical Activity of Idelalisib Alone and in Combination With Rituximab in Elderly Subjects With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 105
- 试验地点
- 6
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This study is to evaluate the safety and clinical activity of idelalisib alone and in combination with rituximab in patients with CLL or SLL.
This Phase 2 study will be the first time that idelalisib is administered to previously untreated patients with hematologic malignancies. Idelalisib has demonstrated clinical activity as a single agent in relapsed or refractory CLL and SLL with acceptable toxicity, which supports its evaluation in previously untreated patients. The study population is limited to patients over 65 years of age because younger patients are generally appropriate for standard immunochemotherapy regimens that are highly active. Since the mechanism of action of idelalisib is distinct from rituximab, it is hypothesized that the combination will be more active than either agent alone. This study will establish initial safety and clinical activity of idelalisib in combination with rituximab in patients with CLL or SLL. Cohort 2 of this study will establish safety and clinical activity of idelalisib alone in subjects with untreated CLL or SLL.
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed CLL or SLL.
- •Presence of measurable lymphadenopathy (defined as the presence of ≥1 nodal lesion that measures ≥ 1.5 cm in the longest diameter (LD) and ≥ 1.0 cm in the longest perpendicular diameter (LPD) as assessed by physical exam, computed tomography (CT) or magnetic resonance imaging (MRI)).
- •CLL - Binet Stage C or Rai Stage III or IV or has active disease defined by meeting at least one of the following criteria:
- •Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
- •Massive (ie, > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
- •Massive nodes (ie, > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
- •Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time of less than 6 months
- •Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
- •At least one of the following disease-related symptoms:
- •Unintentional weight loss ≥ 10% within the previous 6 months
- •Significant fatigue
- •Fevers > 100.4 F for ≥ 2 weeks without other evidence of infection
- •Night sweats for ≥ 1 month without evidence of infection
- •SLL - has active disease as defined above for CLL, except the lymphocytosis criterion does not apply
- •World Health Organization (WHO) Performance Status of ≤ 2
- •For men of child-bearing potential, willing to use adequate methods of contraception for the entire duration of the study
- •Able to provide written informed consent
排除标准
- •Prior therapy for CLL or SLL, except corticosteroids for symptom relief
- •Treatment with a short course of corticosteroids for symptom relief within 1-week prior to Visit 1
- •Known active central nervous system involvement of the malignancy
- •Ongoing active, serious infection requiring systemic therapy. Patients may be receiving prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
- •Serum creatinine ≥ 2.0 mg/dL
- •Serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) or serum transaminases (ie, aspartate aminotransferase (AST), alanine aminotransferase (ALT)) ≥ 2 x upper limit of normal
- •Positive test for human immunodeficiency virus (HIV) antibodies
- •Active hepatitis B or C (confirmed by ribonucleic acid (RNA) test). Patients with serologic evidence of prior exposure are eligible.
- •History of a non-CLL malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to study entry, 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.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Idelalisib
This arm consists of 2 cohorts. Participants in Cohort 1 will receive idelalisib for up to twelve 28-day cycles (or development of unacceptable toxicity) plus rituximab (8 doses through the end of Cycle 2). Upon completion of twelve 28-cycles, participants are eligible to remain on idelalisib in a continuation protocol. Participants in Cohort 2 will receive idelalisib until disease progression or development of unacceptable toxicity.
干预措施: Idelalisib (Drug)
Idelalisib
This arm consists of 2 cohorts. Participants in Cohort 1 will receive idelalisib for up to twelve 28-day cycles (or development of unacceptable toxicity) plus rituximab (8 doses through the end of Cycle 2). Upon completion of twelve 28-cycles, participants are eligible to remain on idelalisib in a continuation protocol. Participants in Cohort 2 will receive idelalisib until disease progression or development of unacceptable toxicity.
干预措施: Rituximab (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 28 Months
ORR was assessed based on standardized International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria as specifically modified for this study to reflect current recommendations which consider the mechanism of action of idelalisib and similar drugs, and was defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator. Based on the CLL response definition in the protocol (modified Hallek 2008), the parameters of lymphadenopathy, liver and/or spleen size, constitutional symptoms, polymorphonuclear leukocytes, circulating clonal B-lymphocytes, platelet count, hemoglobin, and marrow were assessed. * CR: meeting all defined criteria * PR: meeting at least 2 of the criteria of circulating lymphocytes, lymphadenopathy, liver, spleen, or bone marrow (or only lymphadenopathy if liver and spleen normal at baseline) and at least 1 of the criteria for polymorphonuclear leukocytes, platelet count, or hemoglobin.
次要结局
- Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of All Measurable Lesions(Baseline; Weeks 8, 16, 24, 36, 48, 60, 72, 84, 96, 108, and 120)
- Duration of Response(Up to 28 Months)
- Progression-Free Survival(Up to 28 Months)
- Idelalisib Plasma Concentrations (Cohort 1)(Predose and 1.5 hours postdose at Weeks 0, 4, and 24)
- Overall Safety of Idelalisib(Up to 28 Months)
- Lymphadenopathy Response Rate(Baseline and up to 28 Months)
- Idelalisib Plasma Concentrations (Cohort 2)(Predose and 1.5 hours postdose at Weeks 0 and 4 and predose at Weeks 8 and 20)
- Changes in Potential Pharmacodynamic Markers of Drug Activity in Plasma and Whole Blood(Up to 169 days)
- Overall Survival(Up to 28 Months)