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Efficacy and Safety of Idelalisib in Combination With Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia

Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT01659021
Collaborator
(none)
261
Enrollment
80
Locations
2
Arms
68.3
Actual Duration (Months)
3.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the effect of the addition of idelalisib to ofatumumab on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
261 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia
Actual Study Start Date :
Dec 4, 2012
Actual Primary Completion Date :
Aug 15, 2018
Actual Study Completion Date :
Aug 15, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Idelalisib+ofatumumab

Randomized Initial Therapy (24 weeks): Idelalisib + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation. Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.

Drug: Idelalisib
150 mg tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101

    • Drug: Ofatumumab
    Administered intravenously
    Other Names:
  • Arzerra®

    		•
    Active Comparator: Ofatumumab

    Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation. Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.

    Drug: Ofatumumab
    Administered intravenously
    Other Names:
  • Arzerra®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival [Randomization to End of Study (up to 60 months)]

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

    Secondary Outcome Measures

    1. Overall Response Rate [Randomization to End of Study (up to 60 months)]

      Overall response rate was defined as the percentage of participants who achieved a best overall response of complete response or partial response. Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. Partial response was defined as >1 of the following criteria: a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver size, spleen size; plus ≥ 1 of the following: ≥ 1500/μL absolute neutrophil count, > 100000/μL platelets, > 11.0 g/dL hemoglobin or 50% improvement for either of these parameters without transfusions or growth factors. Overall response rate was analyzed using KM estimates.

    2. Lymph Node Response Rate [Randomization to End of Study (up to 60 months)]

      Lymph node response rate was defined as the proportion of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes.

    3. Overall Survival [Randomization to Last Long-Term Follow-Up Visit (up to maximum of 5 years)]

      Overall survival was defined as the interval from randomization to death from any cause. Overall survival was analyzed using KM estimates.

    4. Progression-Free Survival in Subgroup of Participants With Chromosome 17p Deletion and/or TP53 Mutation [Randomization to End of Study (up to 60 months)]

      Progression-free survival in subgroup of participants with chromosome 17p deletion and/or TP53 mutation was analyzed using KM estimates.

    5. Complete Response Rate [Randomization to End of Study (up to 60 months)]

      Complete response rate was defined as the percentage of participants who achieve a complete response and maintain their response for at least 8 weeks (with a 1-week window).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Adults with previously treated recurrent CLL who have measurable lymphadenopathy

    • Require therapy for CLL

    • Have experienced CLL progression < 24 months since the completion of the last prior therapy

    • Have disease that is not refractory to ofatumumab

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Duarte California United States 91010
    2 California Cancer Associates for Research and Excellence (CCARE) Fresno California United States 93720
    3 Kaiser Permanente San Diego California United States 92120
    4 Coastal Integrative Cancer Care San Luis Obispo California United States 93401
    5 Stanford University Medical Center Stanford California United States 94305
    6 Kaiser Permanente Vallejo Medical Center Vallejo California United States 94589
    7 Kaiser Permanente of Colorado Denver Colorado United States 80205
    8 Saint Mary's Regional Cancer Center Grand Junction Colorado United States 81501
    9 Cancer Specialists of North Florida Jacksonville Florida United States 32256
    10 Georgia Regents University Augusta Georgia United States 30912
    11 Montgomery Cancer Center Mount Sterling Kentucky United States 40353
    12 Center for Cancer and Blood Disorders, PC Bethesda Maryland United States 20817
    13 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    14 Washington University Medical Center Saint Louis Missouri United States 63110-1010
    15 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    16 Weill Cornell Medical Center New York New York United States 10065
    17 Oncology Hematology Care, Inc. Cincinnati Ohio United States 45242
    18 The Ohio State University Medical Center Columbus Ohio United States 43202
    19 Oregon Health and Science University Portland Oregon United States 97239
    20 Upstate Oncology Associates Greenville South Carolina United States 29601
    21 Tennessee Oncology, PLLC Chattanooga Tennessee United States 37404
    22 Tenessee Oncology, PLLC Nashville Tennessee United States 37203-1781
    23 Utah Cancer Specialists Salt Lake City Utah United States 84106
    24 Northwest Medical Specialties Tacoma Washington United States 98405
    25 Saint George and Sutherland Hospitals Kogarah New South Wales Australia 2217
    26 Prince of Wales Hospital Randwick New South Wales Australia 2031
    27 Westmead Hospital Westmead New South Wales Australia 2145
    28 Royal Brisbane and Women's Hospital Herston Queensland Australia 4029
    29 Haematology and Oncology Clinics of Australia at Mater Milton Queensland Australia 4064
    30 Ashford Cancer Centre Research Ashford South Australia Australia 5035
    31 Box Hill Hospital Box Hill Victoria Australia 3128
    32 Frankston Hospital Melbourne Victoria Australia 3199
    33 Queen Elizabeth Hospital Woodville Australia 5011
    34 Ziekenhuis Netwerk Antwerpen Antwerpen Belgium 2060
    35 Cliniques Universitaires Saint Luc Brussels Belgium 1200
    36 Universitair Ziekenhuis Gent Ghent Belgium 9000
    37 Universitaire Ziekenhuis Gasthuisberg Leuven Belgium 3000
    38 Tom Baker Cancer Centre Calgary Alberta Canada T2N 2T9
    39 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    40 Cancer Care Manitoba Winnipeg Manitoba Canada R3E 0V9
    41 Hopital Regional De Sudbury Regional Hospital (HRSRH) - Regional Cancer Program (RCP) Sudbury Ontario Canada P3E 5J1
    42 Centre Hospitalier Universitaire de Montréal Montréal Quebec Canada H1T 2M4
    43 Centre Hospitalier Regional de Rimouski Rimouski Quebec Canada G5L 5T1
    44 Saskatchewan Cancer Agency Regina Saskatchewan Canada S4T 1A5
    45 Cancer Care Manitoba Winnipeg Canada R3E 0V9
    46 Aalborg Hospital Aalborg Denmark 9100
    47 Aarhus University Hospital Århus Denmark 8000
    48 Center Hospitalier Universitaire de Bordeaux Pessac Cedex Aquitaine France 33604
    49 Hôpital Saint Louis Paris Cedex 10 Ile-de-france France 75010
    50 Centre Hospitalier de Perpignan Perpignan Languedoc-Roussillon France 66046
    51 Centre Hospitalier Universitaire Nancy Vandoeuvre Limousin, Lorraine France 54511
    52 Centre Hospitalier Universitaire Purpan Toulouse Cedex Midi-pyrenees France 31059
    53 CHRU Clermont- Ferrand CHU Estaing Auvergne France 63000
    54 Centre Hospitalier Universitaire Hôpital Avicenne Ile-de-france France 93009
    55 University College Cork Cork Ireland
    56 Saint James's Hospital Dublin Ireland 8
    57 Collegium Medicum Uniwersytetu Jagiellonskiego w K Kraków Malopolskie Poland 31-501
    58 Wojewódzki Szpital Specjalistyczny im. Janusza Kor Slupsk Pomorskie Poland 76-200
    59 Szpital Specjalistyczny w Brzozowie Brzozow Poland 36-200
    60 Wojewódzki Szpital Specjalistyczny im. Mikolaja Kopernika w Lodzi Lódz Poland 93-510
    61 Centralny Szpital Kliniczny MSW Warszawa Poland 02-507
    62 Samodzielny Publiczny Szpital Kliniczny N1 Klinika Wroclaw Poland 50-367
    63 Hospital Clínic i Provincial Barcelona Spain 08025
    64 Hospital Vall d´Hebrón Barcelona Spain 08035
    65 Hospital Universitario La Princesa Madrid Spain 28006
    66 Hospital Universitario 12 de Octubre Madrid Spain 28041
    67 Hospital Puerta de Hierro Majadahonda Madrid Spain 28222
    68 Hospital Morales Meseguer Murcia Spain 30008
    69 Sunderby Sjukhus Luleå Sweden 971 80
    70 Karolinska University Hospital Solna Stockholm Sweden 171 64
    71 Karolinska University Hospital Huddinge Stockholm Sweden 171 76
    72 Birmingham Heartlands Hospital Birmingham England United Kingdom B9 5ST
    73 Darent Valley Hospital Dartford England United Kingdom DA2 8DA
    74 Royal Surrey County Hospital NHS Trust Guildford England United Kingdom GU2 7XX
    75 Haematology and Transplant Unit Manchester England United Kingdom M20 4BX
    76 Norfolk and Norwich University Hospital Norwich Norfolk United Kingdom NR4 7UY
    77 Saint James's University Hospital Leeds United Kingdom LS9 7TF
    78 University College London London United Kingdom NW1 2PG
    79 University College London London United Kingdom WC1E 6BT
    80 Department of Haematology, Cancer and Haematology Centre, Churchill Hospital (Oxford University Hospitals) Oxford United Kingdom OX3 7LE

    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:
    NCT01659021
    Other Study ID Numbers:
    • GS-US-312-0119
    • 2012-001236-65
    First Posted:
    Aug 7, 2012
    Last Update Posted:
    Aug 14, 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
    CLL
    Chronic Lymphocytic Leukemia
    GS-1101
    CAL-101
    Ofatumumab
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Ofatumumab
    Idelalisib

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in North America, Europe, and Australia. The first participant was screened on 04 December 2012. The last study visit occurred on 15 August 2018.
    Pre-assignment Detail 310 participants were screened.
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of chronic lymphocytic leukemia (CLL), intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone. Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.
    Period Title: Main Study
    STARTED 174 87
    Randomized and Treated 173 86
    COMPLETED 100 50
    NOT COMPLETED 74 37
    Period Title: Main Study
    STARTED 138 69
    COMPLETED 133 65
    NOT COMPLETED 5 4

    Baseline Characteristics

    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab Total
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Total of all reporting groups
    Overall Participants 174 87 261
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    67
    (9.0)
    67
    (9.7)
    67
    (9.2)
    Sex: Female, Male (Count of Participants)
    Female
    50
    28.7%
    25
    28.7%
    75
    28.7%
    Male
    124
    71.3%
    62
    71.3%
    186
    71.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    7
    4%
    3
    3.4%
    10
    3.8%
    Not Hispanic or Latino
    141
    81%
    74
    85.1%
    215
    82.4%
    Unknown or Not Reported
    26
    14.9%
    10
    11.5%
    36
    13.8%
    Race/Ethnicity, Customized (Count of Participants)
    White
    149
    85.6%
    71
    81.6%
    220
    84.3%
    Black or African American
    0
    0%
    4
    4.6%
    4
    1.5%
    Native Hawaiian or Other Pacific Islander
    1
    0.6%
    0
    0%
    1
    0.4%
    Asian
    2
    1.1%
    0
    0%
    2
    0.8%
    Other
    2
    1.1%
    3
    3.4%
    5
    1.9%
    Not Permitted
    20
    11.5%
    9
    10.3%
    29
    11.1%
    Region of Enrollment (Count of Participants)
    Canada
    13
    7.5%
    9
    10.3%
    22
    8.4%
    Sweden
    4
    2.3%
    2
    2.3%
    6
    2.3%
    Belgium
    5
    2.9%
    1
    1.1%
    6
    2.3%
    United States
    64
    36.8%
    29
    33.3%
    93
    35.6%
    Ireland
    7
    4%
    4
    4.6%
    11
    4.2%
    Denmark
    4
    2.3%
    0
    0%
    4
    1.5%
    Poland
    27
    15.5%
    9
    10.3%
    36
    13.8%
    United Kingdom
    11
    6.3%
    6
    6.9%
    17
    6.5%
    Australia
    16
    9.2%
    13
    14.9%
    29
    11.1%
    France
    15
    8.6%
    9
    10.3%
    24
    9.2%
    Spain
    8
    4.6%
    5
    5.7%
    13
    5%
    Time Since Diagnosis (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    101.0
    (60.21)
    94.3
    (52.51)
    98.8
    (57.75)
    17p deletion and/or TP53 mutation (Count of Participants)
    Either
    70
    40.2%
    33
    37.9%
    103
    39.5%
    Neither
    104
    59.8%
    54
    62.1%
    158
    60.5%
    Immunoglobulin heavy chain variable region (IGHV) mutation status (Count of Participants)
    Mutated
    37
    21.3%
    19
    21.8%
    56
    21.5%
    Unmutated
    137
    78.7%
    68
    78.2%
    205
    78.5%
    Disease Status (Count of Participants)
    Refractory
    82
    47.1%
    47
    54%
    129
    49.4%
    Relapsed
    92
    52.9%
    40
    46%
    132
    50.6%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival
    Description Progression-free survival (PFS) was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was CLL progression based on standard criteria (other than lymphocytosis alone) as defined by the 2008 update of the International Workshop on CLL guidelines, ie, appearance of any new lesion; increase by ≥ 50% in the sum of the products of the perpendicular diameters of measured lymph nodes (SPD); new or ≥ 50% enlargement of liver or spleen; transformation to a more aggressive histology (eg, Richter's or prolymphocytic transformation); reduction in the number of blood cells (cytopenia) attributable to CLL. PFS was analyzed using Kaplan-Meier (KM) estimates.
    Time Frame Randomization to End of Study (up to 60 months)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat (ITT) Analysis Set included participants who were randomized in the study regardless of whether they received any study drug(s), or received a different regimen from that to which they were randomized. Treatment assignment was designated according to randomization.
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation
    Measure Participants 174 87
    Median (95% Confidence Interval) [months]
    16.6
    8.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Idelalisib+Ofatumumab, Ofatumumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value is from stratified log-rank test, adjusted for randomization stratification factors (17p deletion/TP53 mutation, immunoglobulin heavy chain variable region (IGHV) mutation, and disease status).
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.26
    Confidence Interval (2-Sided) 95%
    0.18 to 0.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard Ratio and 95% confidence intervals (CI) are from the proportional hazard model, adjusted for randomization stratification factors.
    2. Secondary Outcome
    Title Overall Response Rate
    Description Overall response rate was defined as the percentage of participants who achieved a best overall response of complete response or partial response. Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy. Partial response was defined as >1 of the following criteria: a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver size, spleen size; plus ≥ 1 of the following: ≥ 1500/μL absolute neutrophil count, > 100000/μL platelets, > 11.0 g/dL hemoglobin or 50% improvement for either of these parameters without transfusions or growth factors. Overall response rate was analyzed using KM estimates.
    Time Frame Randomization to End of Study (up to 60 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Analysis Set were analyzed.
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation
    Measure Participants 174 87
    Number (95% Confidence Interval) [percentage of participants]
    75.3
    43.3%
    17.2
    19.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Idelalisib+Ofatumumab, Ofatumumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value was calculated from the Cochran-Mantel-Haenszel (CMH) Chi-square test stratified by stratification factors.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 16.85
    Confidence Interval (2-Sided) 95%
    8.17 to 34.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio and 95% CIs were calculated from the CMH Chi-square test stratified by stratification factors.
    3. Secondary Outcome
    Title Lymph Node Response Rate
    Description Lymph node response rate was defined as the proportion of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes.
    Time Frame Randomization to End of Study (up to 60 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Analysis Set with available data were analyzed.
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation
    Measure Participants 164 81
    Number (95% Confidence Interval) [percentage of participants]
    92.7
    53.3%
    4.9
    5.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Idelalisib+Ofatumumab, Ofatumumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-value was calculated from the CMH Chi-square test stratified by stratification factors.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 483.16
    Confidence Interval (2-Sided) 95%
    94.63 to 2467.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments Odds ratio and 95% CIs were calculated from the CMH Chi-square test stratified by stratification factors.
    4. Secondary Outcome
    Title Overall Survival
    Description Overall survival was defined as the interval from randomization to death from any cause. Overall survival was analyzed using KM estimates.
    Time Frame Randomization to Last Long-Term Follow-Up Visit (up to maximum of 5 years)

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Analysis Set were analyzed.
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone. Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.
    Measure Participants 174 87
    Median (95% Confidence Interval) [months]
    45.2
    39
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Idelalisib+Ofatumumab, Ofatumumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.247
    Comments P-value is from stratified log-rank test, adjusted for randomization stratification factors (17p deletion/TP53 mutation, IGHV mutation, and disease status).
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.79
    Confidence Interval (2-Sided) 95%
    0.54 to 1.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Progression-Free Survival in Subgroup of Participants With Chromosome 17p Deletion and/or TP53 Mutation
    Description Progression-free survival in subgroup of participants with chromosome 17p deletion and/or TP53 mutation was analyzed using KM estimates.
    Time Frame Randomization to End of Study (up to 60 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Analysis Set with chromosome 17p deletion and/or TP53 mutation were analyzed.
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Participants in this group had 17p deletion and/or TP53 mutation. Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Participants in this group had 17p deletion and/or TP53 mutation.
    Measure Participants 70 33
    Median (95% Confidence Interval) [months]
    16.2
    5.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Idelalisib+Ofatumumab, Ofatumumab
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.30
    Confidence Interval (2-Sided) 95%
    0.17 to 0.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio and 95% CIs were calculated using the Cox proportional hazards model without any adjustments.
    6. Secondary Outcome
    Title Complete Response Rate
    Description Complete response rate was defined as the percentage of participants who achieve a complete response and maintain their response for at least 8 weeks (with a 1-week window).
    Time Frame Randomization to End of Study (up to 60 months)

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Analysis Set were analyzed.
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation
    Measure Participants 174 87
    Number [percentage of participants]
    1.1
    0.6%
    0
    0%

    Adverse Events

    Time Frame Adverse Events: Start of Treatment to End of Treatment (up to 60 months) plus 30 days; All-Cause Mortality: Baseline to Last Long-Term Follow-Up Visit (up to maximum of 5 years)
    Adverse Event Reporting Description All-Cause Mortality was assessed in all randomized participants. All other adverse events were assessed in the Safety Analysis Set (participants who received ≥ 1 dose of study treatment, with treatment assignments designated according to the actual treatment received).
    Arm/Group Title Idelalisib+Ofatumumab Ofatumumab
    Arm/Group Description Randomized Initial Therapy (24 weeks): Idelalisib 150 mg tablets twice daily + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone. Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of subject withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.
    All Cause Mortality
    Idelalisib+Ofatumumab Ofatumumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 87/174 (50%) 40/87 (46%)
    Serious Adverse Events
    Idelalisib+Ofatumumab Ofatumumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 136/173 (78.6%) 36/86 (41.9%)
    Blood and lymphatic system disorders
    Anaemia 8/173 (4.6%) 2/86 (2.3%)
    Autoimmune haemolytic anaemia 1/173 (0.6%) 0/86 (0%)
    Disseminated intravascular coagulation 1/173 (0.6%) 0/86 (0%)
    Febrile neutropenia 19/173 (11%) 3/86 (3.5%)
    Granulocytopenia 2/173 (1.2%) 0/86 (0%)
    Leukocytosis 1/173 (0.6%) 0/86 (0%)
    Lymphadenopathy 0/173 (0%) 1/86 (1.2%)
    Neutropenia 13/173 (7.5%) 2/86 (2.3%)
    Pancytopenia 2/173 (1.2%) 0/86 (0%)
    Thrombocytopenia 5/173 (2.9%) 2/86 (2.3%)
    Cardiac disorders
    Acute coronary syndrome 0/173 (0%) 1/86 (1.2%)
    Acute myocardial infarction 2/173 (1.2%) 0/86 (0%)
    Aortic valve disease 1/173 (0.6%) 0/86 (0%)
    Arrhythmia 1/173 (0.6%) 0/86 (0%)
    Atrial fibrillation 3/173 (1.7%) 2/86 (2.3%)
    Bradycardia 1/173 (0.6%) 0/86 (0%)
    Cardiac arrest 1/173 (0.6%) 0/86 (0%)
    Cardiac failure 1/173 (0.6%) 0/86 (0%)
    Cardiogenic shock 2/173 (1.2%) 0/86 (0%)
    Myocardial infarction 2/173 (1.2%) 0/86 (0%)
    Myocardial ischaemia 1/173 (0.6%) 0/86 (0%)
    Palpitations 0/173 (0%) 1/86 (1.2%)
    Right ventricular failure 1/173 (0.6%) 0/86 (0%)
    Ear and labyrinth disorders
    External ear inflammation 1/173 (0.6%) 0/86 (0%)
    Vertigo 1/173 (0.6%) 0/86 (0%)
    Gastrointestinal disorders
    Abdominal pain 7/173 (4%) 1/86 (1.2%)
    Abdominal pain upper 0/173 (0%) 1/86 (1.2%)
    Abdominal wall haematoma 1/173 (0.6%) 0/86 (0%)
    Anal fistula 0/173 (0%) 1/86 (1.2%)
    Colitis 13/173 (7.5%) 0/86 (0%)
    Colitis ulcerative 1/173 (0.6%) 0/86 (0%)
    Diarrhoea 23/173 (13.3%) 0/86 (0%)
    Dysphagia 1/173 (0.6%) 0/86 (0%)
    Gastric haemorrhage 1/173 (0.6%) 0/86 (0%)
    Intestinal obstruction 0/173 (0%) 1/86 (1.2%)
    Large intestine perforation 1/173 (0.6%) 0/86 (0%)
    Mouth haemorrhage 1/173 (0.6%) 0/86 (0%)
    Nausea 3/173 (1.7%) 0/86 (0%)
    Stomatitis 2/173 (1.2%) 0/86 (0%)
    Vomiting 3/173 (1.7%) 0/86 (0%)
    General disorders
    Asthenia 2/173 (1.2%) 1/86 (1.2%)
    Chest pain 2/173 (1.2%) 0/86 (0%)
    Death 1/173 (0.6%) 0/86 (0%)
    General physical health deterioration 1/173 (0.6%) 0/86 (0%)
    Generalised oedema 0/173 (0%) 1/86 (1.2%)
    Impaired self-care 1/173 (0.6%) 0/86 (0%)
    Influenza like illness 1/173 (0.6%) 0/86 (0%)
    Pyrexia 23/173 (13.3%) 1/86 (1.2%)
    Strangulated hernia 1/173 (0.6%) 0/86 (0%)
    Systemic inflammatory response syndrome 1/173 (0.6%) 0/86 (0%)
    Hepatobiliary disorders
    Bile duct obstruction 1/173 (0.6%) 0/86 (0%)
    Cholecystitis 2/173 (1.2%) 0/86 (0%)
    Immune system disorders
    Anaphylactic shock 0/173 (0%) 1/86 (1.2%)
    Infections and infestations
    Abscess 0/173 (0%) 1/86 (1.2%)
    Aspergillus infection 1/173 (0.6%) 0/86 (0%)
    Atypical pneumonia 2/173 (1.2%) 0/86 (0%)
    Bacteraemia 2/173 (1.2%) 0/86 (0%)
    Bacterial sepsis 1/173 (0.6%) 0/86 (0%)
    Biliary sepsis 1/173 (0.6%) 0/86 (0%)
    Bronchitis 4/173 (2.3%) 0/86 (0%)
    Bronchopulmonary aspergillosis 1/173 (0.6%) 0/86 (0%)
    Candida infection 1/173 (0.6%) 0/86 (0%)
    Candida pneumonia 0/173 (0%) 1/86 (1.2%)
    Candida sepsis 1/173 (0.6%) 0/86 (0%)
    Cellulitis 2/173 (1.2%) 0/86 (0%)
    Chronic sinusitis 1/173 (0.6%) 0/86 (0%)
    Cytomegalovirus colitis 1/173 (0.6%) 0/86 (0%)
    Device related infection 0/173 (0%) 1/86 (1.2%)
    Escherichia bacteraemia 0/173 (0%) 1/86 (1.2%)
    Escherichia sepsis 1/173 (0.6%) 0/86 (0%)
    Escherichia urinary tract infection 0/173 (0%) 1/86 (1.2%)
    Folliculitis 1/173 (0.6%) 0/86 (0%)
    Gastroenteritis 1/173 (0.6%) 0/86 (0%)
    Gastroenteritis salmonella 1/173 (0.6%) 0/86 (0%)
    Genital herpes 1/173 (0.6%) 0/86 (0%)
    H1N1 influenza 0/173 (0%) 1/86 (1.2%)
    Herpes simplex 1/173 (0.6%) 0/86 (0%)
    Herpes zoster 1/173 (0.6%) 0/86 (0%)
    Herpes zoster disseminated 1/173 (0.6%) 0/86 (0%)
    Infective exacerbation of chronic obstructive airways disease 1/173 (0.6%) 0/86 (0%)
    Influenza 1/173 (0.6%) 0/86 (0%)
    Listeria sepsis 0/173 (0%) 1/86 (1.2%)
    Lower respiratory tract infection 7/173 (4%) 2/86 (2.3%)
    Lung infection 4/173 (2.3%) 0/86 (0%)
    Neutropenic sepsis 4/173 (2.3%) 2/86 (2.3%)
    Pneumocystis jirovecii infection 1/173 (0.6%) 1/86 (1.2%)
    Pneumocystis jirovecii pneumonia 8/173 (4.6%) 0/86 (0%)
    Pneumonia 27/173 (15.6%) 9/86 (10.5%)
    Progressive multifocal leukoencephalopathy 0/173 (0%) 2/86 (2.3%)
    Pseudomonal bacteraemia 2/173 (1.2%) 0/86 (0%)
    Pseudomonal sepsis 1/173 (0.6%) 0/86 (0%)
    Pseudomonas infection 0/173 (0%) 1/86 (1.2%)
    Respiratory syncytial virus bronchiolitis 1/173 (0.6%) 0/86 (0%)
    Respiratory tract infection 3/173 (1.7%) 2/86 (2.3%)
    Respiratory tract infection bacterial 1/173 (0.6%) 0/86 (0%)
    Rhinovirus infection 1/173 (0.6%) 0/86 (0%)
    Salmonellosis 1/173 (0.6%) 0/86 (0%)
    Sepsis 11/173 (6.4%) 1/86 (1.2%)
    Septic shock 5/173 (2.9%) 1/86 (1.2%)
    Sinusitis 2/173 (1.2%) 0/86 (0%)
    Skin infection 0/173 (0%) 1/86 (1.2%)
    Urinary tract infection 7/173 (4%) 0/86 (0%)
    Urosepsis 1/173 (0.6%) 0/86 (0%)
    Varicella 0/173 (0%) 1/86 (1.2%)
    Vascular device infection 1/173 (0.6%) 0/86 (0%)
    Viral infection 1/173 (0.6%) 0/86 (0%)
    Viral sepsis 1/173 (0.6%) 0/86 (0%)
    Injury, poisoning and procedural complications
    Femoral neck fracture 0/173 (0%) 1/86 (1.2%)
    Femur fracture 0/173 (0%) 1/86 (1.2%)
    Infusion related reaction 3/173 (1.7%) 0/86 (0%)
    Overdose 2/173 (1.2%) 0/86 (0%)
    Upper limb fracture 0/173 (0%) 1/86 (1.2%)
    Investigations
    Alanine aminotransferase increased 1/173 (0.6%) 0/86 (0%)
    Aspartate aminotransferase increased 1/173 (0.6%) 0/86 (0%)
    C-reactive protein increased 1/173 (0.6%) 0/86 (0%)
    Lymphocyte count decreased 1/173 (0.6%) 0/86 (0%)
    Neutrophil count decreased 6/173 (3.5%) 0/86 (0%)
    Platelet count decreased 1/173 (0.6%) 0/86 (0%)
    Transaminases increased 1/173 (0.6%) 0/86 (0%)
    Troponin increased 0/173 (0%) 1/86 (1.2%)
    Weight decreased 1/173 (0.6%) 1/86 (1.2%)
    White blood cell count decreased 1/173 (0.6%) 0/86 (0%)
    Metabolism and nutrition disorders
    Cachexia 1/173 (0.6%) 0/86 (0%)
    Dehydration 6/173 (3.5%) 0/86 (0%)
    Hypercalcaemia 3/173 (1.7%) 1/86 (1.2%)
    Hyperglycaemia 1/173 (0.6%) 0/86 (0%)
    Hyperkalaemia 3/173 (1.7%) 1/86 (1.2%)
    Hypokalaemia 4/173 (2.3%) 0/86 (0%)
    Hyponatraemia 2/173 (1.2%) 0/86 (0%)
    Hypophosphataemia 2/173 (1.2%) 0/86 (0%)
    Pseudohyperkalaemia 1/173 (0.6%) 0/86 (0%)
    Tumour lysis syndrome 1/173 (0.6%) 0/86 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 2/173 (1.2%) 0/86 (0%)
    Haemarthrosis 1/173 (0.6%) 0/86 (0%)
    Muscle haemorrhage 1/173 (0.6%) 0/86 (0%)
    Myalgia 1/173 (0.6%) 0/86 (0%)
    Pain in extremity 1/173 (0.6%) 0/86 (0%)
    Polyarthritis 1/173 (0.6%) 0/86 (0%)
    Soft tissue necrosis 1/173 (0.6%) 0/86 (0%)
    Tenosynovitis 1/173 (0.6%) 0/86 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 1/173 (0.6%) 0/86 (0%)
    Anogenital warts 1/173 (0.6%) 0/86 (0%)
    Basal cell carcinoma 2/173 (1.2%) 0/86 (0%)
    Central nervous system leukaemia 0/173 (0%) 1/86 (1.2%)
    Colon cancer metastatic 1/173 (0.6%) 0/86 (0%)
    Invasive lobular breast carcinoma 1/173 (0.6%) 0/86 (0%)
    Malignant ascites 1/173 (0.6%) 0/86 (0%)
    Malignant melanoma 0/173 (0%) 1/86 (1.2%)
    Mycosis fungoides 1/173 (0.6%) 0/86 (0%)
    Non-small cell lung cancer 2/173 (1.2%) 0/86 (0%)
    Prostate cancer 1/173 (0.6%) 0/86 (0%)
    Renal neoplasm 1/173 (0.6%) 0/86 (0%)
    Squamous cell carcinoma 2/173 (1.2%) 0/86 (0%)
    Nervous system disorders
    Aphasia 1/173 (0.6%) 0/86 (0%)
    Cerebral infarction 1/173 (0.6%) 0/86 (0%)
    Dizziness 1/173 (0.6%) 0/86 (0%)
    Embolic stroke 1/173 (0.6%) 0/86 (0%)
    Facial paralysis 1/173 (0.6%) 0/86 (0%)
    Hemiparesis 2/173 (1.2%) 0/86 (0%)
    Hypotonia 1/173 (0.6%) 0/86 (0%)
    Locked-in syndrome 1/173 (0.6%) 0/86 (0%)
    Peroneal nerve palsy 1/173 (0.6%) 0/86 (0%)
    Sciatica 1/173 (0.6%) 0/86 (0%)
    Transient ischaemic attack 2/173 (1.2%) 0/86 (0%)
    Product Issues
    Device occlusion 1/173 (0.6%) 0/86 (0%)
    Psychiatric disorders
    Bipolar I disorder 0/173 (0%) 1/86 (1.2%)
    Confusional state 1/173 (0.6%) 0/86 (0%)
    Mania 1/173 (0.6%) 0/86 (0%)
    Mental status changes 1/173 (0.6%) 0/86 (0%)
    Renal and urinary disorders
    Acute kidney injury 5/173 (2.9%) 0/86 (0%)
    Chronic kidney disease 1/173 (0.6%) 0/86 (0%)
    Haematuria 2/173 (1.2%) 0/86 (0%)
    Renal failure 3/173 (1.7%) 0/86 (0%)
    Urinary retention 1/173 (0.6%) 0/86 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 2/173 (1.2%) 0/86 (0%)
    Aspiration 1/173 (0.6%) 0/86 (0%)
    Bronchitis chronic 1/173 (0.6%) 0/86 (0%)
    Chronic obstructive pulmonary disease 1/173 (0.6%) 0/86 (0%)
    Cough 2/173 (1.2%) 0/86 (0%)
    Dyspnoea 4/173 (2.3%) 0/86 (0%)
    Interstitial lung disease 2/173 (1.2%) 0/86 (0%)
    Lower respiratory tract inflammation 1/173 (0.6%) 0/86 (0%)
    Lung disorder 1/173 (0.6%) 0/86 (0%)
    Pleural effusion 2/173 (1.2%) 0/86 (0%)
    Pneumonia aspiration 1/173 (0.6%) 0/86 (0%)
    Pneumonitis 7/173 (4%) 0/86 (0%)
    Pulmonary embolism 2/173 (1.2%) 0/86 (0%)
    Pulmonary fibrosis 1/173 (0.6%) 0/86 (0%)
    Pulmonary haemorrhage 1/173 (0.6%) 0/86 (0%)
    Pulmonary oedema 0/173 (0%) 1/86 (1.2%)
    Respiratory arrest 1/173 (0.6%) 0/86 (0%)
    Respiratory failure 6/173 (3.5%) 1/86 (1.2%)
    Skin and subcutaneous tissue disorders
    Dermatitis allergic 1/173 (0.6%) 0/86 (0%)
    Rash 1/173 (0.6%) 0/86 (0%)
    Vascular disorders
    Haematoma 1/173 (0.6%) 0/86 (0%)
    Hypotension 7/173 (4%) 1/86 (1.2%)
    Peripheral artery aneurysm 1/173 (0.6%) 0/86 (0%)
    Other (Not Including Serious) Adverse Events
    Idelalisib+Ofatumumab Ofatumumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 167/173 (96.5%) 79/86 (91.9%)
    Blood and lymphatic system disorders
    Anaemia 38/173 (22%) 7/86 (8.1%)
    Neutropenia 57/173 (32.9%) 14/86 (16.3%)
    Thrombocytopenia 25/173 (14.5%) 5/86 (5.8%)
    Cardiac disorders
    Tachycardia 10/173 (5.8%) 2/86 (2.3%)
    Gastrointestinal disorders
    Abdominal pain 28/173 (16.2%) 5/86 (5.8%)
    Abdominal pain upper 15/173 (8.7%) 4/86 (4.7%)
    Colitis 17/173 (9.8%) 0/86 (0%)
    Constipation 39/173 (22.5%) 13/86 (15.1%)
    Diarrhoea 96/173 (55.5%) 21/86 (24.4%)
    Dyspepsia 13/173 (7.5%) 3/86 (3.5%)
    Gastrooesophageal reflux disease 15/173 (8.7%) 3/86 (3.5%)
    Nausea 62/173 (35.8%) 23/86 (26.7%)
    Stomatitis 9/173 (5.2%) 0/86 (0%)
    Vomiting 29/173 (16.8%) 12/86 (14%)
    General disorders
    Asthenia 27/173 (15.6%) 9/86 (10.5%)
    Chest pain 9/173 (5.2%) 2/86 (2.3%)
    Chills 27/173 (15.6%) 13/86 (15.1%)
    Fatigue 60/173 (34.7%) 24/86 (27.9%)
    Influenza like illness 14/173 (8.1%) 1/86 (1.2%)
    Malaise 10/173 (5.8%) 1/86 (1.2%)
    Oedema peripheral 35/173 (20.2%) 9/86 (10.5%)
    Pain 13/173 (7.5%) 2/86 (2.3%)
    Peripheral swelling 12/173 (6.9%) 1/86 (1.2%)
    Pyrexia 55/173 (31.8%) 19/86 (22.1%)
    Immune system disorders
    Hypogammaglobulinaemia 11/173 (6.4%) 3/86 (3.5%)
    Infections and infestations
    Bronchitis 25/173 (14.5%) 0/86 (0%)
    Lower respiratory tract infection 11/173 (6.4%) 2/86 (2.3%)
    Oral candidiasis 15/173 (8.7%) 0/86 (0%)
    Oral herpes 10/173 (5.8%) 2/86 (2.3%)
    Pneumonia 21/173 (12.1%) 2/86 (2.3%)
    Respiratory tract infection 9/173 (5.2%) 1/86 (1.2%)
    Sinusitis 23/173 (13.3%) 3/86 (3.5%)
    Upper respiratory tract infection 47/173 (27.2%) 9/86 (10.5%)
    Urinary tract infection 18/173 (10.4%) 6/86 (7%)
    Injury, poisoning and procedural complications
    Contusion 18/173 (10.4%) 3/86 (3.5%)
    Infusion related reaction 30/173 (17.3%) 23/86 (26.7%)
    Investigations
    Alanine aminotransferase increased 19/173 (11%) 2/86 (2.3%)
    Aspartate aminotransferase increased 14/173 (8.1%) 2/86 (2.3%)
    Neutrophil count decreased 16/173 (9.2%) 2/86 (2.3%)
    Platelet count decreased 9/173 (5.2%) 1/86 (1.2%)
    Weight decreased 28/173 (16.2%) 5/86 (5.8%)
    Metabolism and nutrition disorders
    Decreased appetite 37/173 (21.4%) 7/86 (8.1%)
    Dehydration 14/173 (8.1%) 0/86 (0%)
    Hyperglycaemia 15/173 (8.7%) 1/86 (1.2%)
    Hypokalaemia 32/173 (18.5%) 4/86 (4.7%)
    Hypomagnesaemia 11/173 (6.4%) 3/86 (3.5%)
    Hyponatraemia 12/173 (6.9%) 1/86 (1.2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 19/173 (11%) 5/86 (5.8%)
    Back pain 28/173 (16.2%) 11/86 (12.8%)
    Muscle spasms 18/173 (10.4%) 2/86 (2.3%)
    Musculoskeletal pain 13/173 (7.5%) 1/86 (1.2%)
    Myalgia 15/173 (8.7%) 1/86 (1.2%)
    Pain in extremity 19/173 (11%) 5/86 (5.8%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 11/173 (6.4%) 3/86 (3.5%)
    Nervous system disorders
    Dizziness 17/173 (9.8%) 5/86 (5.8%)
    Dysgeusia 11/173 (6.4%) 3/86 (3.5%)
    Headache 37/173 (21.4%) 9/86 (10.5%)
    Hypoaesthesia 10/173 (5.8%) 1/86 (1.2%)
    Neuropathy peripheral 11/173 (6.4%) 6/86 (7%)
    Paraesthesia 11/173 (6.4%) 4/86 (4.7%)
    Peripheral sensory neuropathy 6/173 (3.5%) 5/86 (5.8%)
    Psychiatric disorders
    Anxiety 15/173 (8.7%) 2/86 (2.3%)
    Confusional state 10/173 (5.8%) 0/86 (0%)
    Insomnia 30/173 (17.3%) 12/86 (14%)
    Respiratory, thoracic and mediastinal disorders
    Cough 60/173 (34.7%) 18/86 (20.9%)
    Dysphonia 9/173 (5.2%) 1/86 (1.2%)
    Dyspnoea 34/173 (19.7%) 11/86 (12.8%)
    Epistaxis 9/173 (5.2%) 6/86 (7%)
    Nasal congestion 11/173 (6.4%) 6/86 (7%)
    Oropharyngeal pain 17/173 (9.8%) 3/86 (3.5%)
    Productive cough 17/173 (9.8%) 0/86 (0%)
    Rhinorrhoea 12/173 (6.9%) 1/86 (1.2%)
    Skin and subcutaneous tissue disorders
    Dry skin 11/173 (6.4%) 1/86 (1.2%)
    Night sweats 17/173 (9.8%) 10/86 (11.6%)
    Pruritus 21/173 (12.1%) 6/86 (7%)
    Rash 36/173 (20.8%) 7/86 (8.1%)
    Rash maculo-papular 12/173 (6.9%) 0/86 (0%)
    Vascular disorders
    Hypertension 21/173 (12.1%) 6/86 (7%)
    Hypotension 14/173 (8.1%) 5/86 (5.8%)

    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:
    NCT01659021
    Other Study ID Numbers:
    • GS-US-312-0119
    • 2012-001236-65
    First Posted:
    Aug 7, 2012
    Last Update Posted:
    Aug 14, 2019
    Last Verified:
    Aug 1, 2019