Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela )

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effect of the addition of idelalisib (formerly GS-1101) to bendamustine + rituximab (BR) on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL)

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 Bendamustine and 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: Bendamustine
* Drug: Placebo to match idelalisib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Previously treated recurrent CLL Measurable lymphadenopathy Requires therapy for CLL Has experienced CLL progression < 36 months since the completion of the last prior therapy Key Exclusion Criteria: Recent history of a major non-CLL malignancy Evidence of an ongoing infection CLL refractory to bendamustine Concurrent participation in another therapeutic clinical trial NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

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 |
| --- | --- |
| Experimental: Idelalisib+bendamustine+rituximab<br>Participants will receive idelalisib plus bendamustine and rituximab | Drug: Idelalisib<br>* Idelalisib 150 mg administered orally twice daily<br>* Other names: Zydelig®;Drug: Rituximab<br>* Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions<br>* Other names: MabThera;Drug: Bendamustine<br>* Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions<br>* Other names: Treanda®;|
| Placebo Comparator: Placebo to match idelalisib+bendamustine+rituximab<br>Participants will receive placebo to match idelalisib plus bendamustine and rituximab | Drug: Rituximab<br>* Rituximab 375 mg/m^2 on Day 1, then 500 mg/m^2 every 28 days administered intravenously for a maximum of 6 infusions<br>* Other names: MabThera;Drug: Bendamustine<br>* Bendamustine 70 mg/mg^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions<br>* Other names: Treanda®;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 (PFS) | PFS was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. PFS (months) = (minimum (date of disease progression, date of death) - date of randomization + 1)/30.4375. | Up to 84 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR was the percentage of participants who achieved a complete response (CR), CR with incomplete marrow recovery (CRi,) or partial response (PR) and maintained the response for at least 12 weeks. CR was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. PR 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. CRi was defined as all criteria for CR met but with persistent anemia, thrombocytopenia, neutropenia or a hypocellular bone marrow. | Up to 84 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 sum of the products of the greatest perpendicular diameters (SPD) of index lesions. | Up to 84 months | 
| Overall Survival | Overall survival (OS) was defined as the interval from randomization to death from any cause. Overall survival (months) = (date of death - date of randomization + 1)/30.4375. | Up to 84 months | 
| Complete Response Rate | Complete response (CR) rate was defined as the percentage of participants who achieved a CR. | Up to 84 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zydelig, CLL, CAL-101, GS 1101, GS-1101, PI3K, Rituxan, Rituximab, Bendamustine, Leukemia, idelalisib