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Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT01796470
Recruitment Status : Terminated (Study was terminated due to safety measures.)
First Posted : February 21, 2013
Results First Posted : June 2, 2020
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Diffuse Large B-cell Lymphoma
Indolent Non-Hodgkin's Lymphoma
Interventions Drug: Entospletinib
Drug: Idelalisib
Enrollment 66
Recruitment Details Participants were enrolled at study sites in the United States. The first participant was screened on 20 June 2013. The last study visit occurred on 22 December 2016.
Pre-assignment Details 85 participants were screened.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Period Title: Overall Study
Started 35 14 6 3 8
Entospletinib Monotherapy [1] 4 4 0 0 0
Completed 0 0 0 0 0
Not Completed 35 14 6 3 8
Reason Not Completed
Adverse Event             4             2             2             1             3
Death             2             0             0             0             1
Initiated New Therapy             9             0             0             0             2
Lost to Follow-up             0             1             0             0             0
Physician Decision             5             4             1             0             1
Progressive Disease             7             7             3             2             0
Protocol Criteria for Withdrawal             1             0             0             0             0
Withdrawal by Subject             7             0             0             0             1
[1]
Participants who received monotherapy when combination therapy was discontinued.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others Total
Hide Arm/Group Description Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Total of all reporting groups
Overall Number of Baseline Participants 35 14 6 3 8 66
Hide Baseline Analysis Population Description
The Full Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants 14 participants 6 participants 3 participants 8 participants 66 participants
68  (12.9) 64  (13.4) 69  (17.4) 62  (10.8) 69  (8.9) 67  (12.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 14 participants 6 participants 3 participants 8 participants 66 participants
Female 15 6 4 1 5 31
Male 20 8 2 2 3 35
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 35 participants 14 participants 6 participants 3 participants 8 participants 66 participants
Hispanic or Latino 0 0 0 0 0 0
Not Hispanic or Latino 35 12 6 3 8 64
Not Permitted 0 2 0 0 0 2
[1]
Measure Description: Not Permitted Category used, as local regulators did not allow collection of race or ethnicity information.
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 35 participants 14 participants 6 participants 3 participants 8 participants 66 participants
White/Caucasian 27 11 6 3 8 55
Black or African American 5 1 0 0 0 6
Native Hawaiian or Other Pacific Islander 1 0 0 0 0 1
Asian 2 0 0 0 0 2
Other 0 1 0 0 0 1
Not Reported 0 1 0 0 0 1
Karnofsky Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 14 participants 6 participants 3 participants 8 participants 66 participants
40 1 0 0 0 0 1
50 1 0 0 0 0 1
60 2 0 0 1 0 3
70 2 1 1 0 0 4
80 9 7 2 1 5 24
90 14 4 3 1 3 25
100 6 2 0 0 0 8
[1]
Measure Description: Karnofsky Performance Status will be assessed on a scale of 0-100 where 0 indicates death and 100 indicates normal activity.
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR assessed by the Independent Review Committee (IRC), was based on the International Working Group Revised Response Criteria (Cheson, 2012) and investigator's response, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) (or very good partial response [VGPR] or minor response [MR] for participants with LPL/WM). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal immunoglobulin M (IgM) concentration by serum protein electrophoresis (SPEP) respectively.
Time Frame Start of treatment to end of treatment (Up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated due to safety measures. Complete data was not collected for any participant.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description:
Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Hide Description A treatment-emergent Adverse Event (AE) was defined as any AE with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drugs or an AE leading to premature discontinuation of study drug. An AE is any untoward medical occurrence in a clinical investigation where participants administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.
Time Frame First dose date up to the last dose date plus 30 days (maximum duration: 19 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description:
Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Overall Number of Participants Analyzed 35 14 6 3 8
Measure Type: Number
Unit of Measure: percentage of participants
100 100 100 100 100
3.Secondary Outcome
Title Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Hide Description A treatment-emergent laboratory (Hematology, Serum Chemistry and Urinalysis) abnormality was defined as an abnormality that, compared to baseline, worsens by ≥ 1 grade in the period from the first dose of study drug. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening or disabling. If baseline data are missing, then any graded abnormality (i.e., an abnormality that is Grade ≥ 1 in severity) will be considered treatment-emergent. The percentage of participants in each worst postbaseline grade is reported.
Time Frame First dose date up to the last dose date plus 30 days (maximum: 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set were analyzed.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description:

Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm.

Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm.

Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm.

Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/ Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Overall Number of Participants Analyzed 35 14 6 3 8
Measure Type: Number
Unit of Measure: percentage of participants
Neutrophils Count Decreased (Grade 1) 17.1 21.4 0 66.7 25.0
Neutrophils Count Decreased (Grade 2) 20.0 14.3 0 0 25.0
Neutrophils Count Decreased (Grade 3) 14.3 7.1 16.7 0 0
Neutrophils Count Decreased (Grade 4) 11.4 7.1 0 0 25.0
Anemia (Grade 1) 20.0 35.7 16.7 0 0
Anemia (Grade 2) 14.3 7.1 16.7 0 0
Anemia (Grade 3) 5.7 0 16.7 0 0
Anemia (Grade 4) 0 0 0 0 0
Leukocytosis (Grade 1) 0 0 0 0 0
Leukocytosis (Grade 2) 0 0 0 0 0
Leukocytosis (Grade 3) 28.6 0 0 33.3 0
Leukocytosis (Grade 4) 0 0 0 0 0
White Blood Cell Count Decreased (Grade 1) 0 21.4 16.7 0 12.5
WBC Count Decreased (Grade 2) 14.3 0 16.7 33.3 12.5
WBC Count Decreased (Grade 3) 5.7 14.3 0 0 12.5
WBC Count Decreased (Grade 4) 0 0 0 0 12.5
Lymphocyte Count Decreased (Grade 1) 0 0 0 0 0
Lymphocyte Count Decreased (Grade 2) 0 0 16.7 33.3 12.5
Lymphocyte Count Decreased (Grade 3) 5.7 21.4 50.0 0 12.5
Lymphocyte Count Decreased (Grade 4) 0 0 0 33.3 0
Lymphocyte Count Increased (Grade 1) 0 0 0 0 0
Lymphocyte Count Increased (Grade 2) 8.6 7.1 16.7 0 0
Lymphocyte Count Increased (Grade 3) 28.6 0 0 0 12.5
Lymphocyte Count Increased (Grade 4) 0 0 0 0 0
Platelets Count Decreased (Grade 1) 11.4 28.6 16.7 33.3 0
Platelets Count Decreased (Grade 2) 2.9 7.1 0 0 0
Platelets Count Decreased (Grade 3) 5.7 14.3 0 0 0
Platelets Count Decreased (Grade 4) 2.9 0 0 0 0
Alanine Aminotransferase (ALT) Increased (Grade 1) 22.9 7.1 33.3 0 50.0
ALT Increased (Grade 2) 8.6 7.1 0 0 0
ALT Increased (Grade 3) 0 35.7 16.7 33.3 0
ALT Increased (Grade 4) 5.7 0 0 0 12.5
Hypoalbuminemia (Grade 1) 14.3 28.6 0 0 12.5
Hypoalbuminemia (Grade 2) 5.7 0 16.7 33.3 0
Hypoalbuminemia (Grade 3) 0 0 16.7 0 0
Hypoalbuminemia (Grade 4) 0 0 0 0 0
Alkaline Phosphatase (ALP) Increased (Grade 1) 17.1 28.6 33.3 33.3 12.5
ALP Increased (Grade 2) 2.9 0 0 0 12.5
ALP Increased (Grade 3) 0 0 0 0 0
ALP Increased (Grade 4) 0 0 0 0 0
Aspartate Aminotransferase (AST)Increased(Grade 1) 20.0 14.3 50.0 0 37.5
AST Increased (Grade 2) 2.9 14.3 0 33.3 0
AST Increased (Grade 3) 0 28.6 16.7 0 12.5
AST Increased (Grade 4) 5.7 0 0 0 0
Chronic Kidney Disease (Grade 1) 34.3 42.9 50.0 33.3 37.5
Chronic Kidney Disease (Grade 2) 0 7.1 33.3 0 0
Chronic Kidney Disease (Grade 3) 0 0 0 0 0
Chronic Kidney Disease (Grade 4) 0 0 0 0 0
Hyperglycemia (Grade 1) 11.4 7.1 0 0 12.5
Hyperglycemia (Grade 2) 5.7 7.1 0 0 0
Hyperglycemia (Grade 3) 11.4 0 0 0 0
Hyperglycemia (Grade 4) 0 0 0 0 0
Hypoglycemia (Grade 1) 0 14.3 0 33.3 25.0
Hypoglycemia (Grade 2) 0 0 0 0 0
Hypoglycemia (Grade 3) 0 0 0 0 0
Hypoglycemia (Grade 4) 0 0 0 0 0
Hypophosphatemia (Grade 1) 0 0 0 0 0
Hypophosphatemia (Grade 2) 2.9 7.1 0 0 0
Hypophosphatemia (Grade 3) 5.7 0 16.7 0 12.5
Hypophosphatemia (Grade 4) 0 0 0 0 0
Hypokalemia (Grade 1) 20.0 7.1 33.3 0 0
Hypokalemia (Grade 2) 0 0 0 0 0
Hypokalemia (Grade 3) 0 0 0 0 0
Hypokalemia (Grade 4) 0 0 0 0 0
Hyponatremia (Grade 1) 20.0 0 50.0 0 0
Hyponatremia (Grade 2) 0 0 0 0 0
Hyponatremia (Grade 3) 5.7 0 0 0 25.0
Hyponatremia (Grade 4) 0 0 0 0 0
Blood Bilirubin Increased (Grade 1) 17.1 14.3 50.0 0 12.5
Blood Bilirubin Increased (Grade 2) 25.7 14.3 16.7 0 0
Blood Bilirubin Increased (Grade 3) 2.9 0 0 0 0
Blood Bilirubin Increased (Grade 4) 0 0 0 0 0
Proteinuria (Grade 1) 22.9 7.1 0 0 12.5
Proteinuria (Grade 2) 2.9 14.3 0 0 0
Proteinuria (Grade 3) 0 0 0 0 0
Proteinuria (Grade 4) 0 0 0 0 0
4.Secondary Outcome
Title Maximum Tolerated Dose Level
Hide Description Maximum tolerated dose (MTD) is defined as the highest dose level that was consistently well tolerated without dose limiting toxicity (DLT) for the majority of participants time on treatment (ie,> 50%) as determined by the investigator for each participant. DLTs are defined as Grade 4 hematological toxicities persisting for ≥ 14 days or Grade ≥ 3 toxicities of other types.
Time Frame First dose (entospelinib + idelalisib) date up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated due to safety measures. Complete data was not collected for any participant.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description:
Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS was defined as the interval from the first dose of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.
Time Frame Start of treatment to end of treatment (Up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated due to safety measures. Complete data was not collected for any participant.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description:
Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was defined as the interval from the first-time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause.CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.
Time Frame Start of treatment to end of treatment (Up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated due to safety measures. Complete data was not collected for any participant.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description:
Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Time to Response (TTR)
Hide Description TTR was defined as the interval from the first dose of entospletinib/idelalisib to the time response (CR or PR [or VGPR or MR for participants with LPL/WM]) is first achieved. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but < 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.
Time Frame Start of treatment to end of treatment (Up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The study was terminated due to safety measures. Complete data was not collected for any participant.
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description:
Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame First dose date up to the last dose date plus 30 days (maximum duration: 19 months); All-Cause Mortality: Baseline to Last Follow-Up Visit (Up to 3.6 years)
Adverse Event Reporting Description The Safety Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).
 
Arm/Group Title Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Hide Arm/Group Description Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months. Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.
All-Cause Mortality
Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/35 (8.57%)   1/14 (7.14%)   2/6 (33.33%)   2/3 (66.67%)   2/8 (25.00%) 
Hide Serious Adverse Events
Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/35 (68.57%)   2/14 (14.29%)   4/6 (66.67%)   2/3 (66.67%)   5/8 (62.50%) 
Blood and lymphatic system disorders           
Febrile neutropenia  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/8 (25.00%) 
Gastrointestinal disorders           
Abdominal pain  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Abdominal pain upper  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Diarrhoea  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
General disorders           
Drug interaction  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Pyrexia  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Infections and infestations           
Bacteraemia  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Bronchopulmonary aspergillosis  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Fungal infection  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Lung infection  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  1/3 (33.33%)  1/8 (12.50%) 
Pneumonia  1  5/35 (14.29%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Sepsis  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/8 (25.00%) 
Investigations           
Alanine aminotransferase increased  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Aspartate aminotransferase increased  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Blood bilirubin increased  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
International normalised ratio increased  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Lymphocyte count increased  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Nervous system disorders           
Altered state of consciousness  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Cerebrovascular accident  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Psychiatric disorders           
Confusional state  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Renal and urinary disorders           
Hydronephrosis  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Dyspnoea  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/8 (0.00%) 
Hypoxia  1  1/35 (2.86%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Pneumonitis  1  8/35 (22.86%)  0/14 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  1/8 (12.50%) 
Pulmonary embolism  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Respiratory failure  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders           
Erythema multiforme  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Vascular disorders           
Deep vein thrombosis  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Entospletinib + Idelalisib CLL Entospletinib + Idelalisib iNHL: FL Entospletinib + Idelalisib DLBCL Entospletinib + Idelalisib MCL Entospletinib + Idelalisib iNHL: Others
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   34/35 (97.14%)   14/14 (100.00%)   6/6 (100.00%)   3/3 (100.00%)   8/8 (100.00%) 
Blood and lymphatic system disorders           
Anaemia  1  5/35 (14.29%)  0/14 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/8 (0.00%) 
Increased tendency to bruise  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Leukopenia  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Lymphadenopathy  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Lymphopenia  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Neutropenia  1  4/35 (11.43%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Pancytopenia  1  0/35 (0.00%)  1/14 (7.14%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
Thrombocytopenia  1  3/35 (8.57%)  2/14 (14.29%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
Cardiac disorders           
Atrial fibrillation  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Palpitations  1  3/35 (8.57%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Supraventricular tachycardia  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Tachycardia  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Ear and labyrinth disorders           
Ear pain  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Gastrointestinal disorders           
Abdominal pain  1  2/35 (5.71%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Abdominal pain upper  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Abdominal tenderness  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Chapped lips  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Constipation  1  11/35 (31.43%)  2/14 (14.29%)  2/6 (33.33%)  0/3 (0.00%)  0/8 (0.00%) 
Diarrhoea  1  14/35 (40.00%)  2/14 (14.29%)  2/6 (33.33%)  0/3 (0.00%)  1/8 (12.50%) 
Dyschezia  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Dyspepsia  1  3/35 (8.57%)  4/14 (28.57%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Dysphagia  1  1/35 (2.86%)  1/14 (7.14%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Faeces soft  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Flatulence  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Gastritis  1  1/35 (2.86%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Gastrooesophageal reflux disease  1  8/35 (22.86%)  0/14 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  2/8 (25.00%) 
Gingival pain  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Mouth ulceration  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Nausea  1  14/35 (40.00%)  7/14 (50.00%)  4/6 (66.67%)  1/3 (33.33%)  1/8 (12.50%) 
Oral discomfort  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Stomatitis  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/8 (25.00%) 
Vomiting  1  5/35 (14.29%)  2/14 (14.29%)  2/6 (33.33%)  0/3 (0.00%)  1/8 (12.50%) 
General disorders           
Asthenia  1  3/35 (8.57%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Catheter site pain  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Chest discomfort  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Chest pain  1  1/35 (2.86%)  2/14 (14.29%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Chills  1  7/35 (20.00%)  1/14 (7.14%)  3/6 (50.00%)  0/3 (0.00%)  1/8 (12.50%) 
Discomfort  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Fatigue  1  15/35 (42.86%)  6/14 (42.86%)  4/6 (66.67%)  0/3 (0.00%)  3/8 (37.50%) 
Malaise  1  3/35 (8.57%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Mucosal inflammation  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Oedema peripheral  1  5/35 (14.29%)  1/14 (7.14%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
Pain  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Peripheral swelling  1  2/35 (5.71%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Pyrexia  1  10/35 (28.57%)  5/14 (35.71%)  5/6 (83.33%)  1/3 (33.33%)  1/8 (12.50%) 
Hepatobiliary disorders           
Cholelithiasis  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Hyperbilirubinaemia  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Jaundice  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Immune system disorders           
Hypogammaglobulinaemia  1  4/35 (11.43%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Infections and infestations           
Cellulitis  1  2/35 (5.71%)  0/14 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/8 (0.00%) 
Conjunctivitis  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Herpes zoster  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Localised infection  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Mucosal infection  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Nasopharyngitis  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Oesophageal candidiasis  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Oral candidiasis  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
Pharyngitis streptococcal  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Pyelonephritis  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Respiratory tract infection  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Sinusitis  1  5/35 (14.29%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Upper respiratory tract infection  1  6/35 (17.14%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Injury, poisoning and procedural complications           
Contusion  1  2/35 (5.71%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Periorbital haematoma  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Investigations           
Alanine aminotransferase increased  1  6/35 (17.14%)  4/14 (28.57%)  1/6 (16.67%)  1/3 (33.33%)  2/8 (25.00%) 
Aspartate aminotransferase increased  1  7/35 (20.00%)  4/14 (28.57%)  1/6 (16.67%)  0/3 (0.00%)  2/8 (25.00%) 
Blood alkaline phosphatase increased  1  0/35 (0.00%)  0/14 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/8 (0.00%) 
Blood bilirubin increased  1  1/35 (2.86%)  1/14 (7.14%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Blood creatinine increased  1  4/35 (11.43%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Blood glucose increased  1  1/35 (2.86%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
International normalised ratio abnormal  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Neutrophil count decreased  1  4/35 (11.43%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Urine output decreased  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Weight decreased  1  1/35 (2.86%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
White blood cell count decreased  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite  1  5/35 (14.29%)  1/14 (7.14%)  4/6 (66.67%)  0/3 (0.00%)  1/8 (12.50%) 
Hyperuricaemia  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Hypoalbuminaemia  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Hypocalcaemia  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Hypokalaemia  1  2/35 (5.71%)  1/14 (7.14%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Hypomagnesaemia  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Hyponatraemia  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/8 (25.00%) 
Hypophosphataemia  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  2/35 (5.71%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Back pain  1  0/35 (0.00%)  3/14 (21.43%)  1/6 (16.67%)  1/3 (33.33%)  0/8 (0.00%) 
Joint swelling  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Muscle spasms  1  2/35 (5.71%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Muscular weakness  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Musculoskeletal discomfort  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Myalgia  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Neck pain  1  2/35 (5.71%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Osteopenia  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Pain in extremity  1  4/35 (11.43%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Nervous system disorders           
Dizziness  1  5/35 (14.29%)  2/14 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Dysgeusia  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Headache  1  9/35 (25.71%)  4/14 (28.57%)  1/6 (16.67%)  2/3 (66.67%)  1/8 (12.50%) 
Hypoaesthesia  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Neuropathy peripheral  1  2/35 (5.71%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
Paraesthesia  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Peripheral sensory neuropathy  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Presyncope  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/8 (0.00%) 
Syncope  1  1/35 (2.86%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Psychiatric disorders           
Anxiety  1  2/35 (5.71%)  1/14 (7.14%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
Confusional state  1  0/35 (0.00%)  2/14 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Depression  1  1/35 (2.86%)  1/14 (7.14%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Insomnia  1  6/35 (17.14%)  1/14 (7.14%)  2/6 (33.33%)  0/3 (0.00%)  0/8 (0.00%) 
Restlessness  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Suicidal ideation  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Renal and urinary disorders           
Chromaturia  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Haematuria  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Nephrolithiasis  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  10/35 (28.57%)  2/14 (14.29%)  1/6 (16.67%)  1/3 (33.33%)  2/8 (25.00%) 
Dysphonia  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Dyspnoea  1  4/35 (11.43%)  2/14 (14.29%)  1/6 (16.67%)  2/3 (66.67%)  1/8 (12.50%) 
Epistaxis  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  2/8 (25.00%) 
Lung infiltration  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Nasal congestion  1  1/35 (2.86%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Oropharyngeal pain  1  2/35 (5.71%)  2/14 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Pleural effusion  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/8 (0.00%) 
Productive cough  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Rhinitis allergic  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Sinus congestion  1  2/35 (5.71%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Sneezing  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Throat irritation  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Throat tightness  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Upper respiratory tract congestion  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders           
Drug eruption  1  0/35 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/8 (0.00%) 
Dry skin  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Eczema  1  0/35 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Erythema  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  1/8 (12.50%) 
Hyperhidrosis  1  1/35 (2.86%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Night sweats  1  6/35 (17.14%)  1/14 (7.14%)  2/6 (33.33%)  0/3 (0.00%)  0/8 (0.00%) 
Pruritus  1  2/35 (5.71%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Rash  1  7/35 (20.00%)  1/14 (7.14%)  2/6 (33.33%)  0/3 (0.00%)  1/8 (12.50%) 
Rash generalised  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Rash maculo-papular  1  2/35 (5.71%)  1/14 (7.14%)  1/6 (16.67%)  1/3 (33.33%)  2/8 (25.00%) 
Rash pruritic  1  0/35 (0.00%)  2/14 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Vascular disorders           
Flushing  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Hypertension  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
Hypotension  1  3/35 (8.57%)  0/14 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/8 (12.50%) 
Thrombophlebitis superficial  1  0/35 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/3 (0.00%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA (17.1)
Indicates events were collected by systematic assessment
As a result of the early termination of the trial for safety, the efficacy endpoints were not evaluable due to insufficient treatment exposure.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
EMail: GileadClinicalTrials@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01796470    
Other Study ID Numbers: GS-US-339-0103
First Submitted: February 19, 2013
First Posted: February 21, 2013
Results First Submitted: May 18, 2020
Results First Posted: June 2, 2020
Last Update Posted: June 2, 2020