A Randomized, Double-Blind, Placebo-Controlled Study of Idelalisib in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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This Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the effect of idelalisib in combination with rituximab on the onset, magnitude, and duration of tumor control in participants previously treated for chronic lymphocytic leukemia (CLL). Eligible patients will be randomized with a 1:1 ratio into 1 of the 2 treatment arms to receive either idelalisib plus rituximab or placebo plus rituximab. Participants who are tolerating primary study therapy but experience definitive CLL progression are eligible to receive active idelalisib therapy in the extension study, GS-US-312-0117.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Idelalisib
* Drug: Rituximab
* Drug: Placebo to match idelalisib


Participation Criteria
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Eligibility Criteria
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Inclusion: Adult subjects with previously treated recurrent CLL who have measurable lymphadenopathy Require therapy for CLL Have experienced CLL progression < 24 months since the completion of the last prior therapy Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Idelalisib + rituximab<br>Participants will receive idelalisib plus rituximab | Drug: Idelalisib<br>* Idelalisib 150 mg tablet administered orally twice daily<br>* Other names: CAL 101;Drug: Rituximab<br>* Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter<br>* Other names: Rituxan®;|
| Placebo Comparator: Placebo + rituximab<br>Participants will receive placebo to match idelalisib plus rituximab | Drug: Rituximab<br>* Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter<br>* Other names: Rituxan®;Drug: Placebo to match idelalisib<br>* Placebo to match idelalisib administered orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | Progression-free survival was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was CLL progression based on standard criteria (other than lymphocytosis alone) as defined by the 2008 update of the International Workshop on CLL guidelines, ie, appearance of any new lesion; increase by ≥ 50% in the sum of the products of the perpendicular diameters of measured lymph nodes (SPD); new or ≥ 50% enlargement of liver or spleen; transformation to a more aggressive histology (eg, Richter's or prolymphocytic transformation); reduction in the number of blood cells (cytopenia) attributable to CLL. | Up to 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate was defined as the percentage of participants who achieved a best overall response of complete response or partial response. Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. Partial response was defined as >1 of the following criteria: a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver size, spleen size; plus ≥ 1 of the following: ≥ 1500/μL absolute neutrophil count, > 100000/μL platelets, > 11.0 g/dL hemoglobin or 50% improvement for either of these parameters without transfusions or growth factors. | Up to 17 months | 
| Lymph Node Response Rate | Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the SPD of index lymph nodes. | Up to 17 months | 
| Overall Survival | Overall survival was defined as the interval from randomization to death from any cause. | Up to 17 months | 
| Complete Response Rate | Complete response rate was defined as the percentage of participants who achieved a complete response. | Up to 17 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, CAL-101, GS 1101, PI3K, GS-US-312-0117, idelalisib