A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL
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.
|Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL)||Drug: Idelalisib Drug: Rituximab||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||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|
- Overall Response Rate (ORR) [ Time Frame: 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.
- Overall Safety of Idelalisib [ Time Frame: Up to 28 Months ]The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).
- Lymphadenopathy Response Rate [ Time Frame: Baseline and up to 28 Months ]Lymphadenopathy response rate was defined as the percentage of participants with a ≥ 50% reduction from baseline in the sum of the perpendicular diameters of all measurable lesions while receiving study therapy.
- Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of All Measurable Lesions [ Time Frame: Baseline; Weeks 8, 16, 24, 36, 48, 60, 72, 84, 96, 108, and 120 ]
- Duration of Response [ Time Frame: Up to 28 Months ]Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.
- Progression-Free Survival [ Time Frame: Up to 28 Months ]
Progression-free survival (PFS) was defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression or death from any cause.
Progression was defined using the Standardized IWCLL criteria as specifically modified for this study to consider the mechanism of action of idelalisib and similar drugs. The occurrence of any of the following events indicated progression:
- Evidence of any new disease
- Evidence of worsening of index lesions, spleen or liver, or non-index disease
- Decrease in platelet count or hemoglobin that is attributable to CLL and is confirmed by bone marrow biopsy
- Idelalisib Plasma Concentrations (Cohort 1) [ Time Frame: Predose and 1.5 hours postdose at Weeks 0, 4, and 24 ]
- Idelalisib Plasma Concentrations (Cohort 2) [ Time Frame: 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 [ Time Frame: Up to 169 days ]
Changes in potential pharmacodynamic markers of drug activity will include assessments of chemokine and cytokine concentrations, effects on the activity of PI3K and related pathways, and effect on cell migration and other functional outcomes. This endpoint will be assessed at the following time points:
- Idelalisib+Rituximab (Cohort 1): Predose and 1.5 hour postdose on Day 1 and predose on Days 15, 29, 57, 113, and 169
- Idelalisib (Cohort 2): Predose on Days 1, 29, 57, 141
- Overall Survival [ Time Frame: Up to 28 Months ]Overall survival (OS) is defined as the interval from the start of study treatment to death from any cause.
|Actual Study Start Date:||October 2010|
|Study Completion Date:||June 2016|
|Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
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.
Idelalisib 150 mg tablets administered orally twice daily
Other Names:Drug: Rituximab
Rituximab 375 mg/m^2 administered intravenously once weekly x 8 weeks
Other Name: Rituxan
Please refer to this study by its ClinicalTrials.gov identifier: NCT01203930
|United States, California|
|University of California, San Diego, Moores Cancer Center|
|La Jolla, California, United States, 92093-0820|
|Stanford University School of Medicine|
|Stanford, California, United States, 94304|
|United States, New York|
|Columbia University - Herbert Irving Pavilion|
|New York, New York, United States, 10032|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Tennessee|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|The Universtity of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Director:||Gilead Study Director||Gilead Sciences|