An Extension Study for Subjects Who Are Deriving Benefit With Idelalisib (GS-1101; CAL-101) Following Completion of a Prior Idelalisib Study

Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT01090414
Collaborator
(none)
202
18
1
98.9
11.2
0.1

Study Details

Study Description

Brief Summary

This is a long-term safety extension study of idelalisib (GS-1101; CAL-101) in patients with hematologic malignancies who complete other idelalisib studies. It provides the opportunity for patients to continue treatment as long as the patient is deriving clinical benefit. Patients will be followed according to the standard of care as appropriate for their type of cancer. The dose of idelalisib will generally be the same as the dose that was administered at the end of the prior study, but may be titrated up to improve clinical response or down for toxicity. Patients will be withdrawn from the study if they develop progressive disease, unacceptable toxicity related to idelalisib, or if they no longer derive clinical benefit in the opinion of the investigator.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
202 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Extension Study to Investigate the Safety and Durability of Clinical Activity of Idelalisib in Subjects With Hematologic Malignancies
Actual Study Start Date :
Mar 22, 2010
Actual Primary Completion Date :
Jun 18, 2018
Actual Study Completion Date :
Jun 18, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Idelalisib

Participants will receive up to 350 mg of idelalisib twice daily until disease progression or unacceptable toxicity.

Drug: Idelalisib
Idelalisib tablets or capsules administered orally
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate [Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)]

      Overall response rate (ORR) was defined as the percentage of participants who achieve complete response (CR), partial response (PR), or minor response (MR; for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) only).

    2. Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events [Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) plus 30 days]

    Secondary Outcome Measures

    1. Duration of Response [Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)]

      Duration of response (DOR) was defined as the interval from the first documentation of CR, PR, or MR (for LPL/WM) to the earlier of the first documentation of disease progression or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.

    2. Progression-Free Survival [Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)]

      Progression-free survival (PFS) was defined as the interval from start of idelalisib treatment in the parent study to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using KM estimates.

    3. Overall Survival [Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)]

      Overall survival (OS) was defined as the interval from the start of study treatment in the parent study to death from any cause. OS was analyzed using KM estimates.

    4. Time to Response [Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)]

      Time to response (TTR) was defined as the interval from start of study treatment to the first documentation of CR, PR, or MR (for LPL/WM). Analysis only includes participants who achieved complete or partial response (or minor response for LPL/WM participants). No participants in the 101-02 (AML and MM) groups achieved a complete or partial response.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Patients with hematologic malignancies completing a prior idelalisib study with a clinical benefit are eligible

    • Women of childbearing potential must have a negative pregnancy test to be eligible

    • Male patients, and female patients of childbearing potential, must agree to use method(s) of contraception specified in the protocol

    Key Exclusion Criteria:
    • Patients who are unwilling or unable to comply with the protocol are not eligible

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clearview Cancer Institute Huntsville Alabama United States 35805
    2 UCLA Los Angeles California United States 90095-1678
    3 Stanford Cancer Center Palo Alto California United States 94304-5548
    4 Center for Cancer & Blood Disorders, PC Bethesda Maryland United States 20817
    5 Dana-Farber Cancer Institute Boston Massachusetts United States 02115
    6 Washington University School of Medicine Saint Louis Missouri United States 63110
    7 Long Island Jewish medical Center New Hyde Park New York United States 11042
    8 Memorial Sloan-Kettering Cancer Center New York New York United States 10021
    9 Weill Medical College of Cornell New York New York United States 10021
    10 Mount Sinai School of Medicine New York New York United States 10029
    11 The Ohio State University Medical Center Columbus Ohio United States 43210
    12 Oregon Health & Science University Portland Oregon United States 97239
    13 Willamette Valley Cancer Institute and Research Center Springfield Oregon United States 97477
    14 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    15 MD Anderson Cancer and Research Center Houston Texas United States 77030
    16 MD Anderson Cancer Center Houston Texas United States 77030
    17 Yakima Regional Cancer Care Yakima Washington United States 98902
    18 University of Wisconsin Madison Wisconsin United States 53792-5156

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01090414
    Other Study ID Numbers:
    • 101-99
    First Posted:
    Mar 22, 2010
    Last Update Posted:
    Aug 28, 2019
    Last Verified:
    Aug 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the United States. The first participant was screened on 22 March 2010. The last study visit occurred on 18 June 2018.
    Pre-assignment Detail Participants must have been enrolled in a previous Gilead-sponsored study.
    Arm/Group Title 101-02 101-07 101-08 101-10
    Arm/Group Description Participants with chronic lymphocytic leukemia (CLL), indolent non-Hodgkin lymphoma (iNHL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), or multiple myeloma (MM) received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL, iNHL, or MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, everolimus, bortezomib, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or iNHL (specifically, small lymphocytic lymphoma (SLL)) received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Note: Only participants from Cohort 1 were eligible to enter this Study 101-99, so Cohort 2 participants are not presented at all in this record. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment.
    Period Title: Parent Studies
    STARTED 191 241 64 18
    COMPLETED 50 114 43 5
    NOT COMPLETED 141 127 21 13
    Period Title: Parent Studies
    STARTED 48 108 41 5
    COMPLETED 0 0 0 0
    NOT COMPLETED 48 108 41 5

    Baseline Characteristics

    Arm/Group Title 101-02 101-07 101-08 101-10 Total
    Arm/Group Description Participants with CLL, iNHL, MCL, DLBCL, AML, or MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL, iNHL, or MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, everolimus, bortezomib, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or iNHL (specifically, small lymphocytic lymphoma (SLL)) received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment. Total of all reporting groups
    Overall Participants 191 241 64 18 514
    Age, Customized (Count of Participants)
    < 65 years
    86
    45%
    116
    48.1%
    0
    0%
    13
    72.2%
    215
    41.8%
    ≥ 65 years
    105
    55%
    125
    51.9%
    64
    100%
    5
    27.8%
    299
    58.2%
    Sex: Female, Male (Count of Participants)
    Female
    52
    27.2%
    76
    31.5%
    24
    37.5%
    8
    44.4%
    160
    31.1%
    Male
    139
    72.8%
    165
    68.5%
    40
    62.5%
    10
    55.6%
    354
    68.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    1%
    4
    1.7%
    0
    0%
    1
    5.6%
    7
    1.4%
    Not Hispanic or Latino
    167
    87.4%
    234
    97.1%
    64
    100%
    17
    94.4%
    482
    93.8%
    Unknown or Not Reported
    22
    11.5%
    3
    1.2%
    0
    0%
    0
    0%
    25
    4.9%
    Race/Ethnicity, Customized (Count of Participants)
    White
    160
    83.8%
    209
    86.7%
    61
    95.3%
    12
    66.7%
    442
    86%
    Black or African American
    6
    3.1%
    9
    3.7%
    1
    1.6%
    5
    27.8%
    21
    4.1%
    Asian
    1
    0.5%
    11
    4.6%
    1
    1.6%
    1
    5.6%
    14
    2.7%
    Other
    2
    1%
    1
    0.4%
    1
    1.6%
    0
    0%
    4
    0.8%
    Not Reported
    22
    11.5%
    11
    4.6%
    0
    0%
    0
    0%
    33
    6.4%
    Diagnosis Status (Count of Participants)
    Chronic lymphocytic leukemia (CLL)
    54
    28.3%
    115
    47.7%
    59
    92.2%
    0
    0%
    228
    44.4%
    Indolent non-Hodgkin lymphoma (iNHL)
    64
    33.5%
    86
    35.7%
    5
    7.8%
    17
    94.4%
    172
    33.5%
    Mantle cell lymphoma (MCL)
    40
    20.9%
    40
    16.6%
    0
    0%
    0
    0%
    80
    15.6%
    Diffuse large B-cell lymphoma (DLBCL)
    9
    4.7%
    0
    0%
    0
    0%
    0
    0%
    9
    1.8%
    Acute myeloid leukemia (AML)
    12
    6.3%
    0
    0%
    0
    0%
    0
    0%
    12
    2.3%
    Multiple myeloma (MM)
    12
    6.3%
    0
    0%
    0
    0%
    0
    0%
    12
    2.3%
    Missing
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    1
    0.2%

    Outcome Measures

    1. Primary Outcome
    Title Overall Response Rate
    Description Overall response rate (ORR) was defined as the percentage of participants who achieve complete response (CR), partial response (PR), or minor response (MR; for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) only).
    Time Frame Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)

    Outcome Measure Data

    Analysis Population Description
    Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
    Arm/Group Title 101-02 (AML) 101-02 (CLL) 101-02 (DLBCL) 101-02 (iNHL) 101-02 (MCL) 101-02 (MM) 101-07 (CLL) 101-07 (iNHL) 101-07 (MCL) 101-08 (CLL or SLL) 101-10 (iNHL)
    Arm/Group Description Participants with AML received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with DLBCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, everolimus, bortezomib, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or SLL received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment.
    Measure Participants 12 54 9 64 40 12 115 86 40 64 18
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    57.4
    23.8%
    11.1
    17.3%
    48.4
    268.9%
    40.0
    7.8%
    0
    NaN
    81.7
    NaN
    82.6
    NaN
    57.5
    NaN
    96.9
    NaN
    44.4
    NaN
    2. Primary Outcome
    Title Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events
    Description
    Time Frame Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) plus 30 days

    Outcome Measure Data

    Analysis Population Description
    Data presented includes data from both the parent studies and this Study 101-99. For this safety endpoint, data was prespecified to be combined.
    Arm/Group Title 101-02 101-07 101-08 101-10
    Arm/Group Description Participants with CLL or iNHL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL, iNHL, or MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, everolimus, bortezomib, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or SLL received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and entered long-term safety extension study 101-99 to receive the same treatment.
    Measure Participants 191 241 64 18
    Number [percentage of participants]
    98.4
    51.5%
    98.8
    41%
    100.0
    156.3%
    94.4
    524.4%
    3. Secondary Outcome
    Title Duration of Response
    Description Duration of response (DOR) was defined as the interval from the first documentation of CR, PR, or MR (for LPL/WM) to the earlier of the first documentation of disease progression or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.
    Time Frame Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)

    Outcome Measure Data

    Analysis Population Description
    Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
    Arm/Group Title 101-02 (AML) 101-02 (CLL) 101-02 (DLBCL) 101-02 (iNHL) 101-02 (MCL) 101-02 (MM) 101-07 (CLL) 101-07 (iNHL) 101-07 (MCL) 101-08 (CLL or SLL) 101-10 (iNHL)
    Arm/Group Description Participants with AML received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with DLBCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, everolimus, bortezomib, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or SLL received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment.
    Measure Participants 12 54 9 64 40 12 115 86 40 64 18
    Median (95% Confidence Interval) [Months]
    NA
    21.2
    NA
    18.4
    2.7
    NA
    26.6
    42.9
    9.3
    63.8
    14.4
    4. Secondary Outcome
    Title Progression-Free Survival
    Description Progression-free survival (PFS) was defined as the interval from start of idelalisib treatment in the parent study to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using KM estimates.
    Time Frame Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)

    Outcome Measure Data

    Analysis Population Description
    Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
    Arm/Group Title 101-02 (AML) 101-02 (CLL) 101-02 (DLBCL) 101-02 (iNHL) 101-02 (MCL) 101-02 (MM) 101-07 (CLL) 101-07 (iNHL) 101-07 (MCL) 101-08 (CLL or SLL) 101-10 (iNHL)
    Arm/Group Description Participants with AML received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with DLBCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, everolimus, bortezomib, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or SLL received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment.
    Measure Participants 12 54 9 64 40 12 115 86 40 64 18
    Median (95% Confidence Interval) [Months]
    0.9
    15.8
    1.5
    7.6
    3.7
    1
    26.1
    32.8
    11.1
    65.6
    10.2
    5. Secondary Outcome
    Title Overall Survival
    Description Overall survival (OS) was defined as the interval from the start of study treatment in the parent study to death from any cause. OS was analyzed using KM estimates.
    Time Frame Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)

    Outcome Measure Data

    Analysis Population Description
    Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
    Arm/Group Title 101-02 (AML) 101-02 (CLL) 101-02 (DLBCL) 101-02 (iNHL) 101-02 (MCL) 101-02 (MM) 101-07 (CLL) 101-07 (iNHL) 101-07 (MCL) 101-08 (CLL or SLL) 101-10 (iNHL)
    Arm/Group Description Participants with AML received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with DLBCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, everolimus, bortezomib, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or SLL received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment.
    Measure Participants 12 54 9 64 40 12 115 86 40 64 18
    Median (95% Confidence Interval) [Months]
    NA
    NA
    NA
    NA
    NA
    5.2
    NA
    NA
    NA
    NA
    NA
    6. Secondary Outcome
    Title Time to Response
    Description Time to response (TTR) was defined as the interval from start of study treatment to the first documentation of CR, PR, or MR (for LPL/WM). Analysis only includes participants who achieved complete or partial response (or minor response for LPL/WM participants). No participants in the 101-02 (AML and MM) groups achieved a complete or partial response.
    Time Frame Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)

    Outcome Measure Data

    Analysis Population Description
    Data presented includes available data from both the parent studies and this Study 101-99. It was prespecified that data for Study 101-08 be combined for CLL and SLL participants.
    Arm/Group Title 101-02 (AML) 101-02 (CLL) 101-02 (DLBCL) 101-02 (iNHL) 101-02 (MCL) 101-02 (MM) 101-07 (CLL) 101-07 (iNHL) 101-07 (MCL) 101-08 (CLL or SLL) 101-10 (iNHL)
    Arm/Group Description Participants with AML received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with DLBCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, everolimus, bortezomib, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or SLL received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment.
    Measure Participants 0 31 1 31 16 0 94 71 23 62 8
    Median (Inter-Quartile Range) [Months]
    1.9
    4.0
    1.3
    1.1
    1.9
    1.9
    1.9
    1.9
    2.7

    Adverse Events

    Time Frame First dose date in parent study to end of study 101-99 (maximum: up to 91.2 months) plus 30 days
    Adverse Event Reporting Description Adverse events presented occurred during either the parent studies or Study 101-99. Because Study 101-99 was a long-term extension study, the adverse event data was prespecified to be combined and reported based on the participation in the parent studies.
    Arm/Group Title 101-02 101-07 101-08 101-10
    Arm/Group Description Participants with CLL, iNHL, MCL, DLBCL, AML, or MM received idelalisib 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, or 350 mg capsules twice daily during parent study 101-02 (NCT00710528, results reported within this record) and may have entered the long-term safety extension study 101-99 to receive the same treatment. Participants with CLL, iNHL, or MCL received idelalisib 100 mg or 150 mg tablets twice daily with or without rituximab, bendamustine, ofatumumab, fludarabine, everolimus, bortezomib, chlorambucil, and/or lenalidomide during parent study 101-07 (NCT01088048, results reported within this record) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with CLL or SLL received idelalisib 150 mg tablets twice daily with rituximab during parent study 101-08 (NCT01203930) and may have entered long-term safety extension study 101-99 to receive the same treatment. Participants with iNHL received idelalisib 150 mg tablets twice daily during parent study 101-10 (NCT01306643) and may have entered long-term safety extension study 101-99 to receive the same treatment.
    All Cause Mortality
    101-02 101-07 101-08 101-10
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/191 (13.1%) 36/241 (14.9%) 7/45 (15.6%) 2/6 (33.3%)
    Serious Adverse Events
    101-02 101-07 101-08 101-10
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 100/191 (52.4%) 165/241 (68.5%) 45/64 (70.3%) 6/18 (33.3%)
    Blood and lymphatic system disorders
    Anaemia 3/191 (1.6%) 5/241 (2.1%) 1/64 (1.6%) 0/18 (0%)
    Aplasia pure red cell 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Autoimmune haemolytic anaemia 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Autoimmune neutropenia 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Coombs positive haemolytic anaemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Febrile neutropenia 12/191 (6.3%) 23/241 (9.5%) 3/64 (4.7%) 0/18 (0%)
    Haemolytic anaemia 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Immune thrombocytopenic purpura 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Leukocytosis 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Neutropenia 2/191 (1%) 4/241 (1.7%) 1/64 (1.6%) 0/18 (0%)
    Pancytopenia 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Thrombocytopenia 3/191 (1.6%) 6/241 (2.5%) 0/64 (0%) 0/18 (0%)
    Cardiac disorders
    Angina unstable 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Atrial fibrillation 0/191 (0%) 3/241 (1.2%) 0/64 (0%) 1/18 (5.6%)
    Atrioventricular block second degree 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cardiac arrest 0/191 (0%) 4/241 (1.7%) 0/64 (0%) 0/18 (0%)
    Cardiac failure 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Mitral valve incompetence 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Myocardial infarction 1/191 (0.5%) 2/241 (0.8%) 1/64 (1.6%) 0/18 (0%)
    Pulseless electrical activity 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Supraventricular tachycardia 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Tachycardia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Ventricular tachycardia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Ear and labyrinth disorders
    Vertigo 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Endocrine disorders
    Endocrine disorder 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Eye disorders
    Retinal detachment 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Uveitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/191 (1%) 3/241 (1.2%) 0/64 (0%) 0/18 (0%)
    Colitis 8/191 (4.2%) 14/241 (5.8%) 13/64 (20.3%) 0/18 (0%)
    Colitis ischaemic 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Colitis microscopic 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Crohn's disease 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Diarrhoea 9/191 (4.7%) 14/241 (5.8%) 13/64 (20.3%) 0/18 (0%)
    Diarrhoea haemorrhagic 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Dysphagia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Gastrointestinal haemorrhage 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 1/18 (5.6%)
    Gastrointestinal obstruction 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Gastrointestinal perforation 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Gingival bleeding 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Intestinal obstruction 1/191 (0.5%) 2/241 (0.8%) 1/64 (1.6%) 0/18 (0%)
    Large intestinal ulcer 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Mouth haemorrhage 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Nausea 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Neutropenic colitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Odynophagia 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Oesophagitis 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Peptic ulcer 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Rectal haemorrhage 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Retroperitoneal haemorrhage 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Small intestinal obstruction 0/191 (0%) 2/241 (0.8%) 1/64 (1.6%) 0/18 (0%)
    Stomatitis 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Umbilical hernia 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Vomiting 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    General disorders
    Asthenia 1/191 (0.5%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Chest pain 0/191 (0%) 2/241 (0.8%) 1/64 (1.6%) 0/18 (0%)
    Chills 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Fatigue 0/191 (0%) 3/241 (1.2%) 0/64 (0%) 0/18 (0%)
    Generalised oedema 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Impaired healing 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Mucosal inflammation 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Multiple organ dysfunction syndrome 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Pyrexia 6/191 (3.1%) 31/241 (12.9%) 3/64 (4.7%) 0/18 (0%)
    Hepatobiliary disorders
    Cholecystitis 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cholecystitis acute 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cholecystitis chronic 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hepatic failure 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hepatitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Immune system disorders
    Hypersensitivity 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Infections and infestations
    Abdominal wall infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Abscess neck 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Appendicitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Arthritis bacterial 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Aspergillus infection 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Atypical pneumonia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Bacteraemia 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Bacterial infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Bacterial sepsis 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Bronchiolitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Bronchitis 3/191 (1.6%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Bronchopulmonary aspergillosis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Candida infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cellulitis 5/191 (2.6%) 4/241 (1.7%) 2/64 (3.1%) 1/18 (5.6%)
    Cellulitis staphylococcal 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Cerebral aspergillosis 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Clostridium difficile colitis 2/191 (1%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Clostridium difficile infection 0/191 (0%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Corynebacterium bacteraemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cytomegalovirus gastrointestinal infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cytomegalovirus infection 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cytomegalovirus viraemia 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Diverticulitis 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Encephalitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Endophthalmitis 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Enterococcal bacteraemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Enterocolitis infectious 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Escherichia bacteraemia 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Escherichia sepsis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Folliculitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Gangrene 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Gastroenteritis 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Gastroenteritis salmonella 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Groin abscess 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Herpes zoster 0/191 (0%) 4/241 (1.7%) 0/64 (0%) 0/18 (0%)
    Herpes zoster disseminated 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Herpes zoster pharyngitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Histoplasmosis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Human herpesvirus 6 infection 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Hydrocele male infected 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Infection 2/191 (1%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Influenza 1/191 (0.5%) 2/241 (0.8%) 1/64 (1.6%) 0/18 (0%)
    Listeria sepsis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Listeriosis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Lower respiratory tract infection bacterial 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Lung infection 0/191 (0%) 2/241 (0.8%) 1/64 (1.6%) 0/18 (0%)
    Meningitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Meningitis aseptic 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Meningitis enterococcal 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Mycobacterium avium complex infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Neutropenic infection 2/191 (1%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Neutropenic sepsis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Oesophageal candidiasis 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Ophthalmic herpes zoster 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Oral candidiasis 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Otitis media 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Perirectal abscess 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Pneumococcal bacteraemia 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Pneumococcal sepsis 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Pneumocystis jirovecii infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Pneumocystis jirovecii pneumonia 2/191 (1%) 8/241 (3.3%) 1/64 (1.6%) 0/18 (0%)
    Pneumonia 30/191 (15.7%) 40/241 (16.6%) 12/64 (18.8%) 1/18 (5.6%)
    Pneumonia bacterial 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Pneumonia fungal 3/191 (1.6%) 3/241 (1.2%) 0/64 (0%) 0/18 (0%)
    Pneumonia haemophilus 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Pneumonia influenzal 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Pneumonia pneumococcal 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Pneumonia pseudomonal 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Pseudomonal bacteraemia 3/191 (1.6%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Pseudomonas infection 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Respiratory syncytial virus infection 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Sepsis 4/191 (2.1%) 14/241 (5.8%) 1/64 (1.6%) 1/18 (5.6%)
    Sepsis syndrome 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Septic shock 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Sinusitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Sinusitis fungal 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Staphylococcal bacteraemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Staphylococcal infection 2/191 (1%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Streptococcal bacteraemia 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Systemic candida 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Tooth infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Upper respiratory tract infection 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Urinary tract infection 2/191 (1%) 3/241 (1.2%) 3/64 (4.7%) 0/18 (0%)
    Urosepsis 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Vaginal infection 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Viral upper respiratory tract infection 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Vulvovaginitis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Wound infection 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Injury, poisoning and procedural complications
    Arterial injury 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Fall 1/191 (0.5%) 3/241 (1.2%) 0/64 (0%) 0/18 (0%)
    Humerus fracture 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Infusion related reaction 1/191 (0.5%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Pelvic fracture 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Post procedural haemorrhage 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Subarachnoid haemorrhage 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Subdural haematoma 0/191 (0%) 3/241 (1.2%) 0/64 (0%) 0/18 (0%)
    Investigations
    Alanine aminotransferase increased 2/191 (1%) 4/241 (1.7%) 0/64 (0%) 1/18 (5.6%)
    Aspartate aminotransferase increased 2/191 (1%) 3/241 (1.2%) 0/64 (0%) 1/18 (5.6%)
    Blood bilirubin increased 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Blood lactate dehydrogenase increased 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Blood uric acid increased 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Hepatic enzyme increased 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    International normalised ratio increased 1/191 (0.5%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Liver function test increased 2/191 (1%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Transaminases increased 0/191 (0%) 3/241 (1.2%) 0/64 (0%) 1/18 (5.6%)
    Weight decreased 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Dehydration 0/191 (0%) 1/241 (0.4%) 2/64 (3.1%) 0/18 (0%)
    Failure to thrive 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Fluid retention 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Hypercalcaemia 1/191 (0.5%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Hyperglycaemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hyperkalaemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hyperuricaemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hypoglycaemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hypokalaemia 0/191 (0%) 4/241 (1.7%) 0/64 (0%) 0/18 (0%)
    Hyponatraemia 0/191 (0%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Lactic acidosis 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Malnutrition 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Tumour lysis syndrome 0/191 (0%) 4/241 (1.7%) 0/64 (0%) 2/18 (11.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/191 (0.5%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Back pain 0/191 (0%) 0/241 (0%) 2/64 (3.1%) 0/18 (0%)
    Flank pain 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Musculoskeletal pain 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Myalgia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Neck pain 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Polyarthritis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Rhabdomyolysis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Basal cell carcinoma 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Breast cancer 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Chronic myeloid leukaemia 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Colon cancer 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Endometrial adenocarcinoma 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Malignant pleural effusion 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Mantle cell lymphoma 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Metastatic malignant melanoma 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Myelodysplastic syndrome 2/191 (1%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Non-Hodgkin's lymphoma 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Oesophageal squamous cell carcinoma 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Prostate cancer 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Rectal adenocarcinoma 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Renal cell carcinoma 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Richter's syndrome 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Squamous cell carcinoma 2/191 (1%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Squamous cell carcinoma of lung 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Nervous system disorders
    Balance disorder 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Cerebral ischaemia 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Cerebrovascular accident 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Dizziness 0/191 (0%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Embolic stroke 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Haemorrhage intracranial 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Lethargy 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Normal pressure hydrocephalus 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Seizure 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Syncope 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Psychiatric disorders
    Confusional state 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Depression 1/191 (0.5%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Mental status changes 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Suicidal ideation 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Renal and urinary disorders
    Acute kidney injury 7/191 (3.7%) 9/241 (3.7%) 1/64 (1.6%) 0/18 (0%)
    Haematuria 2/191 (1%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Hydronephrosis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Nephrolithiasis 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Renal failure 3/191 (1.6%) 0/241 (0%) 0/64 (0%) 2/18 (11.1%)
    Urethral obstruction 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Urinary retention 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Urinary tract obstruction 0/191 (0%) 2/241 (0.8%) 1/64 (1.6%) 0/18 (0%)
    Reproductive system and breast disorders
    Pelvic pain 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Testicular pain 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Vaginal haemorrhage 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute lung injury 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Acute respiratory failure 1/191 (0.5%) 4/241 (1.7%) 0/64 (0%) 0/18 (0%)
    Atelectasis 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Bronchial secretion retention 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Bronchiectasis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Chronic obstructive pulmonary disease 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Dyspnoea 0/191 (0%) 1/241 (0.4%) 2/64 (3.1%) 0/18 (0%)
    Epistaxis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hypoxia 0/191 (0%) 2/241 (0.8%) 2/64 (3.1%) 1/18 (5.6%)
    Organising pneumonia 2/191 (1%) 1/241 (0.4%) 1/64 (1.6%) 0/18 (0%)
    Pleural effusion 1/191 (0.5%) 4/241 (1.7%) 1/64 (1.6%) 0/18 (0%)
    Pleuritic pain 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Pneumonitis 3/191 (1.6%) 8/241 (3.3%) 3/64 (4.7%) 1/18 (5.6%)
    Pneumothorax 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Pulmonary embolism 6/191 (3.1%) 3/241 (1.2%) 0/64 (0%) 0/18 (0%)
    Pulmonary fibrosis 0/191 (0%) 0/241 (0%) 2/64 (3.1%) 0/18 (0%)
    Pulmonary haemorrhage 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Respiratory distress 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Respiratory failure 1/191 (0.5%) 2/241 (0.8%) 3/64 (4.7%) 0/18 (0%)
    Upper airway obstruction 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Skin and subcutaneous tissue disorders
    Angioedema 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Drug eruption 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Erythema multiforme 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Rash 1/191 (0.5%) 4/241 (1.7%) 0/64 (0%) 0/18 (0%)
    Rash erythematous 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Rash maculo-papular 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Skin ulcer 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Vascular disorders
    Deep vein thrombosis 1/191 (0.5%) 2/241 (0.8%) 0/64 (0%) 0/18 (0%)
    Embolism 1/191 (0.5%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Haematoma 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Haemorrhage 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Hypertension 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 0/18 (0%)
    Hypotension 1/191 (0.5%) 4/241 (1.7%) 0/64 (0%) 0/18 (0%)
    Jugular vein thrombosis 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Orthostatic hypotension 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Peripheral vascular disorder 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Subclavian vein thrombosis 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 0/18 (0%)
    Thrombosis 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Vasculitis necrotising 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 0/18 (0%)
    Other (Not Including Serious) Adverse Events
    101-02 101-07 101-08 101-10
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 183/191 (95.8%) 236/241 (97.9%) 63/64 (98.4%) 16/18 (88.9%)
    Blood and lymphatic system disorders
    Anaemia 31/191 (16.2%) 48/241 (19.9%) 7/64 (10.9%) 0/18 (0%)
    Leukopenia 7/191 (3.7%) 21/241 (8.7%) 0/64 (0%) 0/18 (0%)
    Neutropenia 31/191 (16.2%) 102/241 (42.3%) 5/64 (7.8%) 3/18 (16.7%)
    Thrombocytopenia 25/191 (13.1%) 48/241 (19.9%) 3/64 (4.7%) 2/18 (11.1%)
    Cardiac disorders
    Atrial fibrillation 1/191 (0.5%) 8/241 (3.3%) 1/64 (1.6%) 1/18 (5.6%)
    Atrial tachycardia 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Palpitations 0/191 (0%) 6/241 (2.5%) 1/64 (1.6%) 1/18 (5.6%)
    Ear and labyrinth disorders
    Vertigo 0/191 (0%) 7/241 (2.9%) 1/64 (1.6%) 2/18 (11.1%)
    Eye disorders
    Blepharospasm 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Chalazion 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Conjunctival hyperaemia 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Keratitis 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Photopsia 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Vision blurred 5/191 (2.6%) 7/241 (2.9%) 2/64 (3.1%) 1/18 (5.6%)
    Gastrointestinal disorders
    Abdominal discomfort 2/191 (1%) 5/241 (2.1%) 4/64 (6.3%) 1/18 (5.6%)
    Abdominal pain 14/191 (7.3%) 31/241 (12.9%) 8/64 (12.5%) 2/18 (11.1%)
    Abdominal pain upper 6/191 (3.1%) 7/241 (2.9%) 5/64 (7.8%) 0/18 (0%)
    Colitis 3/191 (1.6%) 8/241 (3.3%) 3/64 (4.7%) 1/18 (5.6%)
    Constipation 23/191 (12%) 49/241 (20.3%) 11/64 (17.2%) 3/18 (16.7%)
    Diarrhoea 58/191 (30.4%) 106/241 (44%) 36/64 (56.3%) 8/18 (44.4%)
    Dyschezia 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Dyspepsia 5/191 (2.6%) 15/241 (6.2%) 3/64 (4.7%) 0/18 (0%)
    Flatulence 8/191 (4.2%) 9/241 (3.7%) 4/64 (6.3%) 3/18 (16.7%)
    Gastrointestinal pain 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Gastrooesophageal reflux disease 4/191 (2.1%) 11/241 (4.6%) 4/64 (6.3%) 1/18 (5.6%)
    Haemorrhoidal haemorrhage 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 1/18 (5.6%)
    Lip discolouration 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Nausea 44/191 (23%) 81/241 (33.6%) 24/64 (37.5%) 7/18 (38.9%)
    Oral pain 2/191 (1%) 3/241 (1.2%) 1/64 (1.6%) 1/18 (5.6%)
    Paraesthesia oral 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 1/18 (5.6%)
    Stomatitis 10/191 (5.2%) 18/241 (7.5%) 8/64 (12.5%) 0/18 (0%)
    Vomiting 23/191 (12%) 33/241 (13.7%) 14/64 (21.9%) 5/18 (27.8%)
    General disorders
    Asthenia 16/191 (8.4%) 21/241 (8.7%) 7/64 (10.9%) 2/18 (11.1%)
    Chest discomfort 1/191 (0.5%) 5/241 (2.1%) 4/64 (6.3%) 0/18 (0%)
    Chest pain 1/191 (0.5%) 9/241 (3.7%) 0/64 (0%) 1/18 (5.6%)
    Chills 31/191 (16.2%) 40/241 (16.6%) 23/64 (35.9%) 2/18 (11.1%)
    Fatigue 63/191 (33%) 85/241 (35.3%) 21/64 (32.8%) 8/18 (44.4%)
    Influenza like illness 0/191 (0%) 2/241 (0.8%) 9/64 (14.1%) 2/18 (11.1%)
    Malaise 1/191 (0.5%) 4/241 (1.7%) 6/64 (9.4%) 2/18 (11.1%)
    Mucosal inflammation 7/191 (3.7%) 15/241 (6.2%) 0/64 (0%) 0/18 (0%)
    Oedema 3/191 (1.6%) 8/241 (3.3%) 4/64 (6.3%) 0/18 (0%)
    Oedema peripheral 18/191 (9.4%) 29/241 (12%) 7/64 (10.9%) 0/18 (0%)
    Pain 6/191 (3.1%) 24/241 (10%) 1/64 (1.6%) 2/18 (11.1%)
    Pyrexia 49/191 (25.7%) 92/241 (38.2%) 26/64 (40.6%) 5/18 (27.8%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 8/191 (4.2%) 4/241 (1.7%) 0/64 (0%) 1/18 (5.6%)
    Infections and infestations
    Candida infection 5/191 (2.6%) 5/241 (2.1%) 0/64 (0%) 1/18 (5.6%)
    Conjunctivitis 2/191 (1%) 4/241 (1.7%) 1/64 (1.6%) 1/18 (5.6%)
    Herpes zoster 4/191 (2.1%) 13/241 (5.4%) 2/64 (3.1%) 0/18 (0%)
    Hordeolum 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 1/18 (5.6%)
    Nasopharyngitis 5/191 (2.6%) 11/241 (4.6%) 3/64 (4.7%) 2/18 (11.1%)
    Pneumonia 6/191 (3.1%) 18/241 (7.5%) 7/64 (10.9%) 0/18 (0%)
    Pneumonia viral 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Sinusitis 10/191 (5.2%) 22/241 (9.1%) 6/64 (9.4%) 0/18 (0%)
    Upper respiratory tract infection 32/191 (16.8%) 38/241 (15.8%) 8/64 (12.5%) 4/18 (22.2%)
    Urinary tract infection 10/191 (5.2%) 15/241 (6.2%) 9/64 (14.1%) 0/18 (0%)
    Injury, poisoning and procedural complications
    Contusion 7/191 (3.7%) 2/241 (0.8%) 1/64 (1.6%) 2/18 (11.1%)
    Fall 2/191 (1%) 5/241 (2.1%) 1/64 (1.6%) 1/18 (5.6%)
    Infusion related reaction 0/191 (0%) 14/241 (5.8%) 7/64 (10.9%) 0/18 (0%)
    Investigations
    Alanine aminotransferase increased 33/191 (17.3%) 52/241 (21.6%) 18/64 (28.1%) 8/18 (44.4%)
    Aspartate aminotransferase increased 35/191 (18.3%) 47/241 (19.5%) 18/64 (28.1%) 8/18 (44.4%)
    Blood alkaline phosphatase increased 12/191 (6.3%) 13/241 (5.4%) 2/64 (3.1%) 0/18 (0%)
    Blood bilirubin increased 2/191 (1%) 6/241 (2.5%) 1/64 (1.6%) 2/18 (11.1%)
    Blood creatinine increased 11/191 (5.8%) 9/241 (3.7%) 3/64 (4.7%) 1/18 (5.6%)
    Blood lactate dehydrogenase increased 4/191 (2.1%) 14/241 (5.8%) 0/64 (0%) 0/18 (0%)
    Blood phosphorus increased 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Blood uric acid increased 0/191 (0%) 1/241 (0.4%) 0/64 (0%) 1/18 (5.6%)
    Glomerular filtration rate decreased 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Hepatic enzyme increased 1/191 (0.5%) 0/241 (0%) 1/64 (1.6%) 1/18 (5.6%)
    Liver function test increased 6/191 (3.1%) 5/241 (2.1%) 6/64 (9.4%) 0/18 (0%)
    Neutrophil count decreased 8/191 (4.2%) 9/241 (3.7%) 5/64 (7.8%) 1/18 (5.6%)
    Transaminases increased 6/191 (3.1%) 5/241 (2.1%) 9/64 (14.1%) 4/18 (22.2%)
    Weight decreased 10/191 (5.2%) 21/241 (8.7%) 7/64 (10.9%) 2/18 (11.1%)
    Metabolism and nutrition disorders
    Decreased appetite 22/191 (11.5%) 41/241 (17%) 9/64 (14.1%) 3/18 (16.7%)
    Dehydration 11/191 (5.8%) 10/241 (4.1%) 6/64 (9.4%) 1/18 (5.6%)
    Hyperglycaemia 11/191 (5.8%) 12/241 (5%) 4/64 (6.3%) 0/18 (0%)
    Hyperuricaemia 0/191 (0%) 10/241 (4.1%) 4/64 (6.3%) 1/18 (5.6%)
    Hypocalcaemia 10/191 (5.2%) 12/241 (5%) 2/64 (3.1%) 0/18 (0%)
    Hypokalaemia 8/191 (4.2%) 35/241 (14.5%) 6/64 (9.4%) 1/18 (5.6%)
    Hypomagnesaemia 1/191 (0.5%) 11/241 (4.6%) 5/64 (7.8%) 0/18 (0%)
    Hyponatraemia 16/191 (8.4%) 7/241 (2.9%) 1/64 (1.6%) 0/18 (0%)
    Hypophosphataemia 12/191 (6.3%) 9/241 (3.7%) 1/64 (1.6%) 0/18 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 10/191 (5.2%) 16/241 (6.6%) 10/64 (15.6%) 2/18 (11.1%)
    Back pain 23/191 (12%) 24/241 (10%) 9/64 (14.1%) 2/18 (11.1%)
    Flank pain 1/191 (0.5%) 3/241 (1.2%) 0/64 (0%) 1/18 (5.6%)
    Haemarthrosis 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 1/18 (5.6%)
    Joint stiffness 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Muscle spasms 8/191 (4.2%) 5/241 (2.1%) 4/64 (6.3%) 2/18 (11.1%)
    Muscular weakness 2/191 (1%) 4/241 (1.7%) 1/64 (1.6%) 1/18 (5.6%)
    Musculoskeletal pain 6/191 (3.1%) 5/241 (2.1%) 4/64 (6.3%) 1/18 (5.6%)
    Myalgia 5/191 (2.6%) 10/241 (4.1%) 4/64 (6.3%) 0/18 (0%)
    Pain in extremity 13/191 (6.8%) 13/241 (5.4%) 6/64 (9.4%) 3/18 (16.7%)
    Nervous system disorders
    Dizziness 15/191 (7.9%) 32/241 (13.3%) 7/64 (10.9%) 0/18 (0%)
    Dysgeusia 6/191 (3.1%) 24/241 (10%) 4/64 (6.3%) 3/18 (16.7%)
    Headache 22/191 (11.5%) 31/241 (12.9%) 15/64 (23.4%) 4/18 (22.2%)
    Hypersomnia 0/191 (0%) 1/241 (0.4%) 1/64 (1.6%) 1/18 (5.6%)
    Lethargy 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 2/18 (11.1%)
    Mental impairment 0/191 (0%) 2/241 (0.8%) 0/64 (0%) 1/18 (5.6%)
    Neuropathy peripheral 4/191 (2.1%) 9/241 (3.7%) 2/64 (3.1%) 1/18 (5.6%)
    Psychiatric disorders
    Agitation 0/191 (0%) 2/241 (0.8%) 1/64 (1.6%) 2/18 (11.1%)
    Anxiety 5/191 (2.6%) 16/241 (6.6%) 4/64 (6.3%) 0/18 (0%)
    Confusional state 4/191 (2.1%) 3/241 (1.2%) 1/64 (1.6%) 1/18 (5.6%)
    Emotional disorder 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Insomnia 17/191 (8.9%) 36/241 (14.9%) 13/64 (20.3%) 5/18 (27.8%)
    Renal and urinary disorders
    Acute kidney injury 4/191 (2.1%) 7/241 (2.9%) 4/64 (6.3%) 0/18 (0%)
    Chromaturia 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Dysuria 3/191 (1.6%) 7/241 (2.9%) 2/64 (3.1%) 1/18 (5.6%)
    Nocturia 2/191 (1%) 4/241 (1.7%) 0/64 (0%) 1/18 (5.6%)
    Pollakiuria 5/191 (2.6%) 3/241 (1.2%) 2/64 (3.1%) 1/18 (5.6%)
    Renal failure 2/191 (1%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 36/191 (18.8%) 81/241 (33.6%) 21/64 (32.8%) 4/18 (22.2%)
    Dysphonia 5/191 (2.6%) 10/241 (4.1%) 1/64 (1.6%) 1/18 (5.6%)
    Dyspnoea 17/191 (8.9%) 42/241 (17.4%) 14/64 (21.9%) 2/18 (11.1%)
    Hypopnoea 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Nasal congestion 3/191 (1.6%) 12/241 (5%) 2/64 (3.1%) 1/18 (5.6%)
    Oropharyngeal pain 7/191 (3.7%) 18/241 (7.5%) 2/64 (3.1%) 1/18 (5.6%)
    Pneumonitis 0/191 (0%) 6/241 (2.5%) 0/64 (0%) 2/18 (11.1%)
    Productive cough 11/191 (5.8%) 20/241 (8.3%) 4/64 (6.3%) 1/18 (5.6%)
    Rhinorrhoea 11/191 (5.8%) 15/241 (6.2%) 1/64 (1.6%) 0/18 (0%)
    Sinus pain 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Skin and subcutaneous tissue disorders
    Acne 1/191 (0.5%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)
    Exfoliative rash 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 3/18 (16.7%)
    Hyperhidrosis 5/191 (2.6%) 1/241 (0.4%) 4/64 (6.3%) 2/18 (11.1%)
    Hyperkeratosis 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 1/18 (5.6%)
    Night sweats 23/191 (12%) 23/241 (9.5%) 10/64 (15.6%) 0/18 (0%)
    Pruritus 5/191 (2.6%) 29/241 (12%) 11/64 (17.2%) 3/18 (16.7%)
    Rash 39/191 (20.4%) 65/241 (27%) 24/64 (37.5%) 5/18 (27.8%)
    Skin fissures 0/191 (0%) 0/241 (0%) 1/64 (1.6%) 1/18 (5.6%)
    Vascular disorders
    Flushing 4/191 (2.1%) 10/241 (4.1%) 4/64 (6.3%) 0/18 (0%)
    Hot flush 1/191 (0.5%) 2/241 (0.8%) 2/64 (3.1%) 1/18 (5.6%)
    Hypertension 6/191 (3.1%) 11/241 (4.6%) 4/64 (6.3%) 0/18 (0%)
    Hypotension 8/191 (4.2%) 7/241 (2.9%) 7/64 (10.9%) 1/18 (5.6%)
    Thrombosis 0/191 (0%) 0/241 (0%) 0/64 (0%) 1/18 (5.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01090414
    Other Study ID Numbers:
    • 101-99
    First Posted:
    Mar 22, 2010
    Last Update Posted:
    Aug 28, 2019
    Last Verified:
    Aug 1, 2019