Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Idelalisib

Antineoplastic Agents, Immunological

Immunologic Factors

Enzyme Inhibitors

Participants will receive idelalisib plus rituximab

Participants will receive placebo to match idelalisib plus rituximab

Idelalisib 150 mg tablet administered orally twice daily

Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m\^2, and 500 mg/m\^2 thereafter

Placebo to match idelalisib administered orally twice daily

Placebo to match idelalisib

Thomas Jahn, MD

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.

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

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

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.

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.

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.

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.

Overall survival was defined as the interval from randomization to death from any cause.

Complete response rate was defined as the percentage of participants who achieved a complete response.

Gilead Sciences

Safety Analysis Set: randomized participants who received at least 1 dose of study drug, with treatment assignments designated according to the actual treatment received.

Idelalisib 150 mg tablet administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m\^2, and 500 mg/m\^2 thereafter)

Idelalisib + Rituximab

Placebo to match idelalisib administered orally twice daily plus rituximab (8 intravenous doses through Week 20: Day 1: 375 mg/m\^2, and 500 mg/m\^2 thereafter)

Placebo + Rituximab

Total

Age, Continuous

< 65 years

≥ 65 years

Age, Customized

Sex: Female, Male

Hispanic or Latino

Not Hispanic or Latino

Not Permitted

Race/Ethnicity, Customized

White

Black or African American

Other

France

Germany

Italy

United Kingdom

United States

Region of Enrollment

Classifies patients according to their functional impairment. Scores range from 0-100; the lower the score, the worse the survival for most serious illnesses.

Karnofsky Performance Status

Time Since Diagnosis

Rai Stage 0

Rai Stage 1

Rai Stage 2

Rai Stage 3

Rai Stage 4

Missing

Rai staging categorizes the disease progression of chronic lymphocytic leukemia (CLL), with classifications of low- (Stage 0), intermediate- (Stage 1 and 2), and high-risk (Stages 3 and 4) categories. Rai Stage 0: high number of lymphocytes in the blood (lymphocytosis) only. Rai Stage 1: lymphocytosis with enlarged lymphoid tissues (lymphadenopathy). Rai Stage 2: lymphocytosis with enlarged liver (hepatomegaly) or spleen (splenomegaly). Rai Stage 3: lymphocytosis with low red blood cell count (anemia). Rai Stage 4: lymphocytosis with low number of blood platelets (thrombocytopenia).

Rai Stage at Screening

Binet Stage A

Binet Stage B

Binet Stage C

Binet staging classifies CLL according to the number of lymphoid tissues involved, as well as the presence of anemia or thrombocytopenia. Stage A: fewer than three areas of enlarged lymphoid tissue; enlarged lymph nodes of the neck, underarms, and groin, as well as the spleen, are each considered "one group" whether unilateral (one-sided) or bilateral (on both sides). Binet Stage B: more than three areas of enlarged lymphoid tissue. Binet Stage C: anemia plus thrombocytopenia.

Binet Stage at Screening

ITT Analysis Set: randomized participants with treatment group designated according to initial randomization.

Following a recommendation by an independent Data Monitoring Committee (DMC), the study was stopped early due to highly statistically significant results for the primary efficacy endpoint of progression-free survival.

Clinical Trial Disclosures

Intent-to-Treat (ITT) Analysis Set: randomized participants with treatment group designated according to initial randomization.

Progression-Free Survival

Overall Response Rate

ITT Analysis Set: randomized participants with treatment group designated according to initial randomization

Lymph Node Response Rate

Overall Survival

Complete Response Rate

Overall Study

Bendamustine Hydrochloride

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants will receive idelalisib plus bendamustine and rituximab

Participants will receive placebo to match idelalisib plus bendamustine and rituximab

Idelalisib 150 mg administered orally twice daily

Rituximab 375 mg/m\^2 on Day 1, then 500 mg/m\^2 every 28 days administered intravenously for a maximum of 6 infusions

Bendamustine 70 mg/mg\^2/day on 2 consecutive days every 28 days administered intravenously for a maximum of 12 infusions

Bendamustine

Gilead Study Director

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)

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

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

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.

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.

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.

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.

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.

Complete response (CR) rate was defined as the percentage of participants who achieved a CR.

The Safety Analysis Set included all participants who received \>=1 dose of study treatment, with treatment group assignments designated according to the actual treatment received.

Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + rituximab 375 mg/m\^2 on Day 1, then 500 mg/m\^2 every 28 days administered intravenously for a total of 6 infusions + bendamustine 70 mg/mg\^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions).

Idelalisib + Bendamustine + Rituximab

Placebo to match idelalisib administered orally twice daily + rituximab 375 mg/m\^2 on Day 1, then 500 mg/ m\^2 every 28 days administered intravenously for a total of 6 infusions + bendamustine 70 mg/m\^2/infusion on days 1 and 2 of each 28 day cycle administered intravenously for a total of 6 cycles (12 infusions).

Placebo + Bendamustine + Rituximab

Race

Ethnicity

Romania

Hungary

Czechia

Portugal

Russia

Spain

Greece

Canada

Turkey

Belgium

Ireland

Poland

Australia

Croatia

New Zealand

The intent-to-treat (ITT) Analysis Set included all participants randomized in the study regardless of whether study drug was administered and with treatment group designated according to initial randomization.

Gilead Clinical Study Information Center

Idelalisib 150 mg tablet administered orally twice daily (until the earliest of participant withdrawal from study, definitive progression of chronic lymphocytic leukemia (CLL), intolerable toxicity, pregnancy, substantial noncompliance with study procedures, or study discontinuation) + rituximab 375 mg/m\^2 on Day 1, then 500 mg/m\^2 every 28 days administered intravenously for a total of 6 infusions + bendamustine 70 mg/mg\^2/infusion on days 1 and 2 of each 28 day cycle, administered intravenously for a total of 6 cycles (12 infusions).

The intent-to-treat (ITT) Analysis Set included all participants randomised in the study regardless of whether study drug was administered and with treatment group designated according to initial randomisation.

Progression-Free Survival (PFS)

Participants in the ITT Analysis Set were analyzed.

Overall Response Rate (ORR)

Participants in the ITT Analysis Set with available data were analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Randomized, Double-Blind, Placebo-Controlled Study of Idelalisib in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL)	NCT01539512	Chronic Lymphoc...	Idelalisib Rituximab Placebo to matc...	18 Years -	Gilead Sciences
Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela )	NCT01569295	Chronic Lymphoc...	Idelalisib Rituximab Bendamustine Placebo to matc...	18 Years -	Gilead Sciences
Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) (Tugela )	NCT01569295	Chronic Lymphoc...	Idelalisib Rituximab Bendamustine Placebo to matc...	18 Years -	Gilead Sciences

Spots Global Cancer Trial Database for placebo to match idelalisib