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)
|Study Design:||Intervention Model: Single Group Assignment
Masking: 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 [ Time Frame: Up to 7 years ]Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as evaluated according to standard criteria.
- Type, frequency, severity, and relationship to study therapy of any adverse events (AEs) or abnormalities of physical findings, laboratory tests, drug discontinuations due to AEs or serious adverse events (SAEs) [ Time Frame: Up to 7 years ]This composite endpoint will measure the safety profile of idelalisib.
- Lymphadenopathy response rate [ Time Frame: Up to 7 years ]Lymphadenopathy response rate is defined as the proportion of participants with a ≥ 50% reduction from baseline in the sum of the perpendicular diameters of all measurable lesions while receiving study therapy.
- Change from baseline in the sum of the perpendicular diameters of all measurable lesions [ Time Frame: Up to 7 years ]
- Duration of response [ Time Frame: Up to 7 years ]Duration of response (DOR) is defined as the interval from the first documentation of CR or PR to the first documentation of definitive disease progression or death from any cause.
- Progression-free survival [ Time Frame: Up to 7 years ]Progression-free survival (PFS) is defined as the interval from the first dose of study drug to the first documentation of definitive disease progression or death from any cause.
- Overall survival [ Time Frame: Up to 7 years ]Overall survival (OS) is defined as the interval from the start of study treatment to death from any cause.
- Trough and 1.5 hour postdose plasma concentrations of idelalisib [ Time Frame: Up to 169 days ]
Trough and 1.5 hour postdose plasma concentrations of idelalisib will be assessed at the following time points:
- Idelalisib+Rituximab (Cohort 1): Predose and 1.5 hour postdose on Days 1, 29, and 169
- Idelalisib (Cohort 2): Predose and 1.5 hour postdose on Days 1 and 29 and predose on Days 57 and 141
- 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
|Study Start Date:||October 2010|
|Study Completion Date:||May 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). 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:||Ronald Dubowy, MD||Gilead Sciences|