GENUINE: Ublituximab in Combination With Ibrutinib Versus Ibrutinib Alone in Participants With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)

Sponsor
TG Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02301156
Collaborator
(none)
126
88
2
62.1
1.4
0

Study Details

Study Description

Brief Summary

This study evaluates the effect of the addition of ublituximab, a novel monoclonal antibody, to ibrutinib compared to ibrutinib alone on antitumor activity, as measured by the overall response rate (ORR = CR [complete response] + PR [partial response]) in previously treated Chronic Lymphocytic Leukemia (CLL) participants with high-risk cytogenetic features. Half of the participants will receive ublituximab in combination with ibrutinib, while the other half will receive ibrutinib alone.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
126 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Study to Assess the Efficacy and Safety of Ublituximab in Combination With Ibrutinib Compared to Ibrutinib Alone, in Patients With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date :
Jan 27, 2015
Actual Primary Completion Date :
Apr 1, 2020
Actual Study Completion Date :
Apr 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ublituximab + Ibrutinib

Participants will receive ublituximab intravenous (IV) infusion, up to 150 milligrams (mg) once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 62 months along with ibrutinib 420 mg capsules, orally, once daily (QD) in each 28-day cycle for up to 62 months.

Drug: Ublituximab
Administered as an IV infusion
Other Names:
  • TG-1101
  • Drug: Ibrutinib
    Administered orally
    Other Names:
  • IMBRUVICA
  • Active Comparator: Ibrutinib

    Participants will receive ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 62 months.

    Drug: Ibrutinib
    Administered orally
    Other Names:
  • IMBRUVICA
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [Up to 62 months]

      ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: No evidence of new disease; Absolute lymphocyte count(ALC)<4x10^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters(cm) in longest diameter(LD); Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; Absolute neutrophil count(ANC)>1.5x10^9/L,platelets≥100x10^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR criteria: No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC<4x10^9/L or >=50% decrease from baseline in sum of products(SPD) of target nodal lesions; splenomegaly; hepatomegaly;>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; response in any 1:ANC>1.5x10^9/L,platelets>100x10^9/L,Hgb>110g/L or >=50% increase over baseline in any of these.

    Secondary Outcome Measures

    1. Complete Response (CR) Rate [Up to 62 months]

      The CR rate was defined as the percentage of participants who achieved CR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L.

    2. Minimum Residual Disease (MRD) Negativity Rate [Up to 62 months]

      MRD negativity rate was defined as the percentage of participants who were MRD negative post-baseline. If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow.

    3. Progression-Free Survival (PFS) [From the randomization until the first documentation of PD or death whichever occurs first or up to 62 months]

      PFS was defined as the time from the date of randomization until the date of first documentation of definitive disease progression (PD) or date of death from any cause, whichever occurs first. PD requires at least one of the following: New nodes >1.5 cm in the LD and >1.0 in longest perpendicular diameter (LPD), new or recurrent hepatomegaly or splenomegaly, new or reappearance of an unequivocal extra-nodal lesion, ≥50% increase from the nadir in the sum of products of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 g/L decrease from the highest on-study Hgb.

    4. Duration of Response (DOR) [From the first dose of study drug until the first documentation of PD or death whichever occurs first or up to 62 months]

      DOR:Interval from first documentation of CR/PR to first documentation of PD or death from any cause.CR:ALC<4x10^9/L;Regression to normal of target nodal masses,nodal non-target disease,and no detectable non-nodal,non-target disease;Normal spleen,liver size;Morphologically negative bone marrow,No lymphoid nodules;ANC>1.5x10^9/L,Platelets≥100x10^9/L,Hgb≥110 g/L.PR:Response in 2 or more:ALC<4x10^9/L,>=50% drop from baseline in ALC or SPD of target nodal lesions,Hepatosplenomegaly,>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules;Response in 1 or more:ANC>1.5x10^9/L,Platelets>100x10^9/L,Hgb>110 g/L or >=50% increase over baseline in any.PD:Response in 1 or more:new nodes,Hepatosplenomegaly,unequivocal extra-nodal lesion;≥50% increase from nadir in SPD of target lesions or LD of node/extra-nodal mass or Splenic/Hepatic size,Unequivocal increase in non-target disease,More aggressive histology;Drop of >50% in platelets/>20g/L in Hgb from highest on-study count.

    5. Time to Response (TTR) [From the randomization up to 62 months]

      TTR was defined as the interval from the randomization to the first documentation of CR or PR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L. PR criteria: No evidence of new disease; Response in 2 of following when abnormal at baseline: ALC<4 x 10^9/L or >=50% decrease from baseline in SPD of target nodal lesions; splenomegaly; hepatomegaly; >=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; and Response in 1 of the following: ANC>1.5 x 10^9/L, platelets>100 x 10^9/L, Hgb>110 g/L or >=50% increase over baseline in any of these.

    6. Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE) [From the first dose up to 30 days after the last dose of study drug (up to 57.3 months)]

      An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Previously treated Chronic Lymphocytic Leukemia (CLL) requiring treatment

    • At least one high-risk cytogenetic feature defined by the presence of 17p deletion, 11q deletion and/or p53 mutation

    • Eastern Cooperative Oncology Group (ECOG) score of 0 to 2

    Exclusion Criteria:
    • Any major surgery, chemotherapy or immunotherapy within the last 21 days

    • Evidence of hepatitis B virus, hepatitis C virus or known human immunodeficiency virus (HIV) infection

    • Autologous hematologic stem cell transplant within 3 months of study entry. Prior Allogeneic hematologic stem cell transplant is excluded

    • Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation)

    • Previous therapy with ibrutinib, or any drug that specifically inhibits Bruton's tyrosine kinase (BTK)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 TG Therapeutics Investigational Trial Site Huntsville Alabama United States 35805
    2 TG Therapeutics Investigational Trial Site Mobile Alabama United States 36604
    3 TG Therapeutics Investigational Trial Site Chandler Arizona United States 85224
    4 TG Therapeutics Investigational Trial Site Tucson Arizona United States 85710
    5 TG Therapeutics Investigational Trial Site Fayetteville Arkansas United States 72703
    6 TG Therapeutics Investigational Trial Site Jonesboro Arkansas United States 72401
    7 TG Therapeutics Investigational Trial Site Fullerton California United States 92835
    8 TG Therapeutics Investigational Trial Site Greenbrae California United States 94904
    9 TG Therapeutics Investigational Trial Site Los Angeles California United States 90045
    10 TG Therapeutics Investigational Trial Site Pismo Beach California United States 93449
    11 TG Therapeutics Investigational Trial Site Pleasanton California United States 94588
    12 TG Therapeutics Investigational Trial Site Santa Barbara California United States 93105
    13 TG Therapeutics Investigational Trial Site Aurora Colorado United States 80012
    14 TG Therapeutics Investigational Trial Site Bridgeport Connecticut United States 06606
    15 TG Therapeutics Investigational Trial Site Stamford Connecticut United States 06904
    16 TG Therapeutics Investigational Trial Site Newark Delaware United States 19173
    17 TG Therapeutics Investigational Trial Site Boca Raton Florida United States 33486
    18 TG Therapeutics Investigational Trial Site Fort Myers Florida United States 33905
    19 TG Therapeutics Investigational Trial Site Orange City Florida United States 32763
    20 TG Therapeutics Investigational Trial Site Pensacola Florida United States 32504
    21 TG Therapeutics Investigational Trial Site Saint Petersburg Florida United States 33709
    22 TG Therapeutics Investigational Trial Site West Palm Beach Florida United States 33401
    23 TG Therapeutics Investigational Trial Site Albany Georgia United States 31701
    24 TG Therapeutics Investigational Trial Site Newnan Georgia United States 30265
    25 TG Therapeutics Investigational Trial Site Evanston Illinois United States 60201
    26 TG Therapeutics Investigational Trial Site Maywood Illinois United States 60153
    27 TG Therapeutics Investigational Trial Site Niles Illinois United States 60714
    28 TG Therapeutics Investigational Trial Site Urbana Illinois United States 61801
    29 TG Therapeutics Investigational Trial Site Fort Wayne Indiana United States 46804
    30 TG Therapeutics Investigational Trial Site Indianapolis Indiana United States 46237
    31 TG Therapeutics Investigational Trial Site Ames Iowa United States 50010
    32 TG Therapeutics Investigational Trial Site Cedar Rapids Iowa United States 52403
    33 TG Therapeutics Investigational Trial Site Westwood Kansas United States 66205
    34 TG Therapeutics Investigational Trial Site Baton Rouge Louisiana United States 70816
    35 TG Therapeutics Investigational Trial Site New Orleans Louisiana United States 70121
    36 TG Therapeutics Investigational Trial Site Baltimore Maryland United States 21202
    37 TG Therapeutics Investigational Trial Site Baltimore Maryland United States 21215
    38 TG Therapeutics Investigational Trial Site Bethesda Maryland United States 20817
    39 TG Therapeutics Investigational Trial Site Columbia Maryland United States 21044
    40 TG Therapeutics Investigational Trial Site Salisbury Maryland United States 21801
    41 TG Therapeutics Investigational Trial Site Boston Massachusetts United States 02111
    42 TG Therapeutics Investigational Trial Site Springfield Massachusetts United States 01199
    43 TG Therapeutics Investigational Trial Site Worcester Massachusetts United States 01608
    44 TG Therapeutics Investigational Trial Site Detroit Michigan United States 48202
    45 TG Therapeutics Investigational Trial Site Coon Rapids Minnesota United States 55433
    46 TG Therapeutics Investigational Trial Site Saint Louis Park Minnesota United States 55416
    47 TG Therapeutics Investigational Trial Site Lincoln Nebraska United States 68510
    48 TG Therapeutics Investigational Trial Site Omaha Nebraska United States 68130
    49 TG Therapeutics Investigational Trial Site Lebanon New Hampshire United States 03756
    50 TG Therapeutics Investigational Trial Site East Brunswick New Jersey United States 08816
    51 TG Therapeutics Investigational Trial Site Howell New Jersey United States 07731
    52 TG Therapeutics Investigational Trial Site Morristown New Jersey United States 07962
    53 TG Therapeutics Investigational Trial Site Pompton Plains New Jersey United States 07444
    54 TG Therapeutics Investigational Trial Site Somerville New Jersey United States 08876
    55 TG Therapeutics Investigational Trial Site New York New York United States 10019
    56 TG Therapeutics Investigational Trial Site Syracuse New York United States 13210
    57 TG Therapeutics Investigational Trial Site Charlotte North Carolina United States 28204
    58 TG Therapeutics Investigational Trial Site Durham North Carolina United States 27710
    59 TG Therapeutics Investigational Trial Site Raleigh North Carolina United States 27607
    60 TG Therapeutics Investigational Trial Site Canton Ohio United States 44718
    61 TG Therapeutics Investigational Trial Site Cincinnati Ohio United States 45242
    62 TG Therapeutics Investigational Trial Site Cleveland Ohio United States 44106
    63 TG Therapeutics Investigational Trial Site Portland Oregon United States 97213-2982
    64 TG Therapeutics Investigational Trial Site Portland Oregon United States 97227
    65 TG Therapeutics Investigational Trial Site Springfield Oregon United States 97477
    66 TG Therapeutics Investigational Trial Site Camp Hill Pennsylvania United States 17011
    67 TG Therapeutics Investigational Trial Site Philadelphia Pennsylvania United States 19104
    68 TG Therapeutics Investigational Trial Site Pawtucket Rhode Island United States 02860
    69 TG Therapeutics Investigational Trial Site Greenville South Carolina United States 29607
    70 TG Therapeutics Investigational Trial Site Greenville South Carolina United States 29615
    71 TG Therapeutics Investigational Trial Site Sioux Falls South Dakota United States 57105
    72 TG Therapeutics Investigational Trial Site Watertown South Dakota United States 57201
    73 TG Therapeutics Investigational Trial Site Memphis Tennessee United States 38120
    74 TG Therapeutics Investigational Trial Site Nashville Tennessee United States 37203
    75 TG Therapeutics Investigational Trial Site Austin Texas United States 78705
    76 TG Therapeutics Investigational Trial Site Dallas Texas United States 75230
    77 TG Therapeutics Investigational Trial Site Denton Texas United States 76201
    78 TG Therapeutics Investigational Trial Site Fort Sam Houston Texas United States 78234
    79 TG Therapeutics Investigational Trial Site San Antonio Texas United States 78229
    80 TG Therapeutics Investigational Trial Site Tyler Texas United States 75702
    81 TG Therapeutics Investigational Trial Site Webster Texas United States 77598-4420
    82 TG Therapeutics Investigational Trial Site Ogden Utah United States 84403
    83 TG Therapeutics Investigational Trial Site Blacksburg Virginia United States 24060
    84 TG Therapeutics Investigational Trial Site Richmond Virginia United States 23230
    85 TG Therapeutics Investigational Trial Site Seattle Washington United States 98104
    86 TG Therapeutics Investigational Trial Site Spokane Washington United States 99216
    87 TG Therapeutics Investigational Trial Site Vancouver Washington United States 98683
    88 TG Therapeutics Investigational Trial Site Ashkelon Israel

    Sponsors and Collaborators

    • TG Therapeutics, Inc.

    Investigators

    • Study Chair: Jeff Sharman, MD, Willamette Valley Cancer Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    TG Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02301156
    Other Study ID Numbers:
    • UTX-IB-301
    First Posted:
    Nov 25, 2014
    Last Update Posted:
    May 20, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details A total of 126 participants were enrolled at investigative sites in Israel and the United States (US) from 27 January 2015 to 01 April 2020.
    Pre-assignment Detail Participants with previously treated Chronic Lymphocytic Leukemia (CLL) who had at least one high-risk cytogenetic abnormality were enrolled and randomized in a 1:1 ratio to receive either ublituximab in combination with ibrutinib or ibrutinib alone.
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab intravenous (IV) infusion, up to 150 milligrams (mg) once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, once daily (QD) in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Period Title: Overall Study
    STARTED 64 62
    Intent to Treat (ITT) Population 64 62
    Safety Population 59 58
    COMPLETED 11 10
    NOT COMPLETED 53 52

    Baseline Characteristics

    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib Total
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months. Total of all reporting groups
    Overall Participants 64 62 126
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    67.0
    67.2
    67.1
    Sex: Female, Male (Count of Participants)
    Female
    20
    31.3%
    16
    25.8%
    36
    28.6%
    Male
    44
    68.8%
    46
    74.2%
    90
    71.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    1.6%
    0
    0%
    1
    0.8%
    Not Hispanic or Latino
    62
    96.9%
    59
    95.2%
    121
    96%
    Unknown or Not Reported
    1
    1.6%
    3
    4.8%
    4
    3.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    7
    10.9%
    6
    9.7%
    13
    10.3%
    White
    56
    87.5%
    55
    88.7%
    111
    88.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    1.6%
    1
    1.6%
    2
    1.6%
    Region of Enrollment (Count of Participants)
    Israel
    1
    1.6%
    0
    0%
    1
    0.8%
    United States
    63
    98.4%
    62
    100%
    125
    99.2%

    Outcome Measures

    1. Primary Outcome
    Title Overall Response Rate (ORR)
    Description ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: No evidence of new disease; Absolute lymphocyte count(ALC)<4x10^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters(cm) in longest diameter(LD); Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; Absolute neutrophil count(ANC)>1.5x10^9/L,platelets≥100x10^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR criteria: No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC<4x10^9/L or >=50% decrease from baseline in sum of products(SPD) of target nodal lesions; splenomegaly; hepatomegaly;>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; response in any 1:ANC>1.5x10^9/L,platelets>100x10^9/L,Hgb>110g/L or >=50% increase over baseline in any of these.
    Time Frame Up to 62 months

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all randomized participants.
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Measure Participants 64 62
    Number [percentage of participants]
    84.4
    131.9%
    69.4
    111.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ublituximab + Ibrutinib, Ibrutinib
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0463
    Comments
    Method Cochran-Mantel-Haenszel
    Comments P-value was estimated by Cochran-Mantel-Haenszel (CMH) test stratified by the randomization strata prior lines of therapy.
    2. Secondary Outcome
    Title Complete Response (CR) Rate
    Description The CR rate was defined as the percentage of participants who achieved CR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L.
    Time Frame Up to 62 months

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all randomized participants.
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Measure Participants 64 62
    Number [percentage of participants]
    18.8
    29.4%
    4.8
    7.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ublituximab + Ibrutinib, Ibrutinib
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0159
    Comments
    Method Cochran-Mantel-Haenszel
    Comments P-value was estimated by CMH test stratified by the randomization strata prior lines of therapy.
    3. Secondary Outcome
    Title Minimum Residual Disease (MRD) Negativity Rate
    Description MRD negativity rate was defined as the percentage of participants who were MRD negative post-baseline. If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow.
    Time Frame Up to 62 months

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all randomized participants.
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Measure Participants 64 62
    Number (95% Confidence Interval) [percentage of participants]
    45.3
    70.8%
    9.7
    15.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ublituximab + Ibrutinib, Ibrutinib
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Cochran-Mantel-Haenszel
    Comments P-value was estimated using CMH test stratified by the randomization strata prior lines of therapy.
    Method of Estimation Estimation Parameter Rate Difference
    Estimated Value 35.64
    Confidence Interval (2-Sided) 95%
    21.39 to 49.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments 95% Confidence Interval (CI) was estimated using Clopper-Pearson method based on the binomial distribution.
    4. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS was defined as the time from the date of randomization until the date of first documentation of definitive disease progression (PD) or date of death from any cause, whichever occurs first. PD requires at least one of the following: New nodes >1.5 cm in the LD and >1.0 in longest perpendicular diameter (LPD), new or recurrent hepatomegaly or splenomegaly, new or reappearance of an unequivocal extra-nodal lesion, ≥50% increase from the nadir in the sum of products of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 g/L decrease from the highest on-study Hgb.
    Time Frame From the randomization until the first documentation of PD or death whichever occurs first or up to 62 months

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all randomized participants.
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Measure Participants 64 62
    Median (95% Confidence Interval) [months]
    NA
    47.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ublituximab + Ibrutinib, Ibrutinib
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0961
    Comments
    Method Log Rank
    Comments P-value was estimated by stratified log rank test and the stratification was based on the randomization strata prior lines of therapy.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.573
    Confidence Interval (2-Sided) 95%
    0.295 to 1.113
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified Hazard Ratio and 95% CI were estimated using Cox proportion hazard model and the stratification was based on the randomization strata prior lines of therapy.
    5. Secondary Outcome
    Title Duration of Response (DOR)
    Description DOR:Interval from first documentation of CR/PR to first documentation of PD or death from any cause.CR:ALC<4x10^9/L;Regression to normal of target nodal masses,nodal non-target disease,and no detectable non-nodal,non-target disease;Normal spleen,liver size;Morphologically negative bone marrow,No lymphoid nodules;ANC>1.5x10^9/L,Platelets≥100x10^9/L,Hgb≥110 g/L.PR:Response in 2 or more:ALC<4x10^9/L,>=50% drop from baseline in ALC or SPD of target nodal lesions,Hepatosplenomegaly,>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules;Response in 1 or more:ANC>1.5x10^9/L,Platelets>100x10^9/L,Hgb>110 g/L or >=50% increase over baseline in any.PD:Response in 1 or more:new nodes,Hepatosplenomegaly,unequivocal extra-nodal lesion;≥50% increase from nadir in SPD of target lesions or LD of node/extra-nodal mass or Splenic/Hepatic size,Unequivocal increase in non-target disease,More aggressive histology;Drop of >50% in platelets/>20g/L in Hgb from highest on-study count.
    Time Frame From the first dose of study drug until the first documentation of PD or death whichever occurs first or up to 62 months

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Population (included all randomized participants) who achieved either CR or PR were analyzed.
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Measure Participants 54 43
    Median (95% Confidence Interval) [months]
    NA
    39.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ublituximab + Ibrutinib, Ibrutinib
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1486
    Comments
    Method Log Rank
    Comments P-value was estimated by stratified log rank test and the stratification was based on the randomization strata prior lines of therapy.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.569
    Confidence Interval (2-Sided) 95%
    0.263 to 1.234
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified Hazard Ratio and 95% CI were estimated using Cox proportion hazard model and the stratification was based on the randomization strata prior lines of therapy.
    6. Secondary Outcome
    Title Time to Response (TTR)
    Description TTR was defined as the interval from the randomization to the first documentation of CR or PR. CR criteria: No evidence of new disease; ALC <4 x 10^9/L; Regression of all target nodal masses to normal size ≤1.5 cm in the LD; Normal spleen and liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; ANC >1.5 x 10^9/L, platelets ≥100 x 10^9/L, Hgb ≥110 g/L. PR criteria: No evidence of new disease; Response in 2 of following when abnormal at baseline: ALC<4 x 10^9/L or >=50% decrease from baseline in SPD of target nodal lesions; splenomegaly; hepatomegaly; >=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; and Response in 1 of the following: ANC>1.5 x 10^9/L, platelets>100 x 10^9/L, Hgb>110 g/L or >=50% increase over baseline in any of these.
    Time Frame From the randomization up to 62 months

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT Population (included all randomized participants) who achieved either CR or PR were analyzed.
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Measure Participants 54 43
    Median (95% Confidence Interval) [months]
    2.0
    3.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Ublituximab + Ibrutinib, Ibrutinib
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method Log Rank
    Comments P-value was estimated by stratified log rank test and the stratification was based on the randomization strata prior lines of therapy.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 2.163
    Confidence Interval (2-Sided) 95%
    1.399 to 3.344
    Parameter Dispersion Type:
    Value:
    Estimation Comments Stratified Hazard Ratio and 95% CI were estimated using Cox proportion hazard model and the stratification was based on the randomization strata prior lines of therapy.
    7. Secondary Outcome
    Title Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE)
    Description An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related.
    Time Frame From the first dose up to 30 days after the last dose of study drug (up to 57.3 months)

    Outcome Measure Data

    Analysis Population Description
    Safety Population included all participants who received at least one dose of study medication (ublituximab + ibrutinib or ibrutinib alone).
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    Measure Participants 59 58
    Number [percentage of participants]
    100
    156.3%
    100
    161.3%

    Adverse Events

    Time Frame Adverse Events: From the first dose up to 30 days after the last dose of study drug (up to 57.3 months); All-Cause Mortality: From the first dose up to end of study (up to 62 months)
    Adverse Event Reporting Description Safety Population included all participants who received at least one dose of study medication (ublituximab + ibrutinib or ibrutinib alone).
    Arm/Group Title Ublituximab + Ibrutinib Ibrutinib
    Arm/Group Description Participants received ublituximab IV infusion, up to 150 mg once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 54.6 months along with ibrutinib 420 mg capsules, orally, QD in each 28-day cycle for up to 51.6 months. Participants received ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 56.3 months.
    All Cause Mortality
    Ublituximab + Ibrutinib Ibrutinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/59 (8.5%) 9/58 (15.5%)
    Serious Adverse Events
    Ublituximab + Ibrutinib Ibrutinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/59 (64.4%) 31/58 (53.4%)
    Blood and lymphatic system disorders
    Febrile neutropenia 3/59 (5.1%) 1/58 (1.7%)
    Cardiac disorders
    Atrial fibrillation 4/59 (6.8%) 1/58 (1.7%)
    Angina pectoris 1/59 (1.7%) 0/58 (0%)
    Atrial flutter 1/59 (1.7%) 0/58 (0%)
    Cardiac arrest 1/59 (1.7%) 1/58 (1.7%)
    Coronary artery disease 1/59 (1.7%) 0/58 (0%)
    Pericarditis 1/59 (1.7%) 0/58 (0%)
    Acute myocardial infarction 0/59 (0%) 1/58 (1.7%)
    Cardiac failure 0/59 (0%) 2/58 (3.4%)
    Cardiac failure congestive 0/59 (0%) 1/58 (1.7%)
    Cardiomyopathy 0/59 (0%) 1/58 (1.7%)
    Congenital, familial and genetic disorders
    Vitello-intestinal duct remnant 1/59 (1.7%) 0/58 (0%)
    Eye disorders
    Retinal tear 0/59 (0%) 1/58 (1.7%)
    Gastrointestinal disorders
    Diarrhoea 2/59 (3.4%) 0/58 (0%)
    Dysphagia 2/59 (3.4%) 0/58 (0%)
    Gastric haemorrhage 1/59 (1.7%) 0/58 (0%)
    Abdominal distension 0/59 (0%) 1/58 (1.7%)
    Colitis 0/59 (0%) 1/58 (1.7%)
    Duodenitis 0/59 (0%) 1/58 (1.7%)
    Pancreatitis 0/59 (0%) 1/58 (1.7%)
    Retroperitoneal haemorrhage 0/59 (0%) 1/58 (1.7%)
    Small intestinal obstruction 0/59 (0%) 1/58 (1.7%)
    General disorders
    Pyrexia 2/59 (3.4%) 0/58 (0%)
    Fatigue 0/59 (0%) 1/58 (1.7%)
    Infections and infestations
    Pneumonia 6/59 (10.2%) 4/58 (6.9%)
    Sepsis 3/59 (5.1%) 1/58 (1.7%)
    Cellulitis 2/59 (3.4%) 0/58 (0%)
    Bacteraemia 1/59 (1.7%) 1/58 (1.7%)
    Cellulitis staphylococcal 1/59 (1.7%) 0/58 (0%)
    Meningitis aseptic 1/59 (1.7%) 0/58 (0%)
    Otitis externa 1/59 (1.7%) 0/58 (0%)
    Pneumocystis jirovecii pneumonia 1/59 (1.7%) 1/58 (1.7%)
    Pneumonia mycoplasmal 1/59 (1.7%) 0/58 (0%)
    Sinusitis bacterial 1/59 (1.7%) 0/58 (0%)
    Streptococcal sepsis 1/59 (1.7%) 0/58 (0%)
    Bronchitis 0/59 (0%) 1/58 (1.7%)
    Device related infection 0/59 (0%) 1/58 (1.7%)
    Diverticulitis 0/59 (0%) 1/58 (1.7%)
    Gastroenteritis 0/59 (0%) 1/58 (1.7%)
    Herpes simplex 0/59 (0%) 1/58 (1.7%)
    Periorbital cellulitis 0/59 (0%) 1/58 (1.7%)
    Periorbital infection 0/59 (0%) 1/58 (1.7%)
    Streptococcal bacteraemia 0/59 (0%) 1/58 (1.7%)
    Upper respiratory tract infection 0/59 (0%) 1/58 (1.7%)
    Injury, poisoning and procedural complications
    Fall 1/59 (1.7%) 0/58 (0%)
    Incision site pain 1/59 (1.7%) 0/58 (0%)
    Subdural haematoma 1/59 (1.7%) 0/58 (0%)
    Splenic rupture 0/59 (0%) 1/58 (1.7%)
    Metabolism and nutrition disorders
    Hypokalaemia 2/59 (3.4%) 0/58 (0%)
    Hyponatraemia 2/59 (3.4%) 1/58 (1.7%)
    Failure to thrive 1/59 (1.7%) 0/58 (0%)
    Tumour lysis syndrome 1/59 (1.7%) 0/58 (0%)
    Type 1 diabetes mellitus 1/59 (1.7%) 0/58 (0%)
    Musculoskeletal and connective tissue disorders
    Neck pain 1/59 (1.7%) 0/58 (0%)
    Back pain 0/59 (0%) 1/58 (1.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gallbladder neoplasm 1/59 (1.7%) 0/58 (0%)
    Myelodysplastic syndrome 1/59 (1.7%) 0/58 (0%)
    Papillary renal cell carcinoma 1/59 (1.7%) 0/58 (0%)
    Prostate cancer 1/59 (1.7%) 0/58 (0%)
    Squamous cell carcinoma 1/59 (1.7%) 0/58 (0%)
    Squamous cell carcinoma of head and neck 1/59 (1.7%) 0/58 (0%)
    Squamous cell carcinoma of lung 1/59 (1.7%) 1/58 (1.7%)
    Basal cell carcinoma 0/59 (0%) 2/58 (3.4%)
    Bowens disease 0/59 (0%) 1/58 (1.7%)
    Malignant melanoma 0/59 (0%) 1/58 (1.7%)
    Squamous cell carcinoma of skin 0/59 (0%) 2/58 (3.4%)
    Tumour flare 0/59 (0%) 1/58 (1.7%)
    Nervous system disorders
    Seizure 1/59 (1.7%) 0/58 (0%)
    Cerebral haemorrhage 0/59 (0%) 1/58 (1.7%)
    Cerebral infarction 0/59 (0%) 1/58 (1.7%)
    Syncope 0/59 (0%) 2/58 (3.4%)
    Transient ischaemic attack 0/59 (0%) 1/58 (1.7%)
    Psychiatric disorders
    Confusional state 0/59 (0%) 1/58 (1.7%)
    Major depression 0/59 (0%) 1/58 (1.7%)
    Mental status changes 0/59 (0%) 2/58 (3.4%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 2/59 (3.4%) 1/58 (1.7%)
    Acute respiratory failure 1/59 (1.7%) 1/58 (1.7%)
    Bronchiectasis 1/59 (1.7%) 0/58 (0%)
    Haemoptysis 1/59 (1.7%) 0/58 (0%)
    Pneumonia aspiration 1/59 (1.7%) 0/58 (0%)
    Pneumonitis 1/59 (1.7%) 0/58 (0%)
    Acute pulmonary oedema 0/59 (0%) 1/58 (1.7%)
    Dyspnoea 0/59 (0%) 2/58 (3.4%)
    Hypoxia 0/59 (0%) 1/58 (1.7%)
    Pleural effusion 0/59 (0%) 2/58 (3.4%)
    Pulmonary granuloma 0/59 (0%) 1/58 (1.7%)
    Vascular disorders
    Hypertension 1/59 (1.7%) 0/58 (0%)
    Other (Not Including Serious) Adverse Events
    Ublituximab + Ibrutinib Ibrutinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 59/59 (100%) 57/58 (98.3%)
    Blood and lymphatic system disorders
    Increased tendency to bruise 2/59 (3.4%) 3/58 (5.2%)
    Leukocytosis 2/59 (3.4%) 5/58 (8.6%)
    Thrombocytopenia 12/59 (20.3%) 4/58 (6.9%)
    Neutropenia 15/59 (25.4%) 7/58 (12.1%)
    Anaemia 17/59 (28.8%) 12/58 (20.7%)
    Cardiac disorders
    Atrial fibrillation 5/59 (8.5%) 4/58 (6.9%)
    Palpitations 7/59 (11.9%) 5/58 (8.6%)
    Eye disorders
    Dry eye 5/59 (8.5%) 2/58 (3.4%)
    Gastrointestinal disorders
    Abdominal discomfort 2/59 (3.4%) 3/58 (5.2%)
    Dysphagia 3/59 (5.1%) 2/58 (3.4%)
    Oral pain 3/59 (5.1%) 2/58 (3.4%)
    Haemorrhoids 4/59 (6.8%) 1/58 (1.7%)
    Abdominal distension 5/59 (8.5%) 1/58 (1.7%)
    Abdominal pain upper 5/59 (8.5%) 0/58 (0%)
    Gastrooesophageal reflux disease 5/59 (8.5%) 4/58 (6.9%)
    Dry mouth 9/59 (15.3%) 7/58 (12.1%)
    Abdominal pain 10/59 (16.9%) 10/58 (17.2%)
    Dyspepsia 12/59 (20.3%) 5/58 (8.6%)
    Stomatitis 12/59 (20.3%) 7/58 (12.1%)
    Vomiting 13/59 (22%) 4/58 (6.9%)
    Constipation 14/59 (23.7%) 11/58 (19%)
    Nausea 24/59 (40.7%) 19/58 (32.8%)
    Diarrhoea 34/59 (57.6%) 26/58 (44.8%)
    General disorders
    Non-cardiac chest pain 3/59 (5.1%) 2/58 (3.4%)
    Influenza like illness 4/59 (6.8%) 4/58 (6.9%)
    Asthenia 5/59 (8.5%) 4/58 (6.9%)
    Pain 5/59 (8.5%) 3/58 (5.2%)
    Oedema peripheral 11/59 (18.6%) 16/58 (27.6%)
    Chills 15/59 (25.4%) 4/58 (6.9%)
    Pyrexia 17/59 (28.8%) 8/58 (13.8%)
    Fatigue 23/59 (39%) 22/58 (37.9%)
    Immune system disorders
    Hypogammaglobulinaemia 9/59 (15.3%) 3/58 (5.2%)
    Infections and infestations
    Conjunctivitis 1/59 (1.7%) 3/58 (5.2%)
    Eye infection 3/59 (5.1%) 1/58 (1.7%)
    Fungal infection 3/59 (5.1%) 0/58 (0%)
    Onychomycosis 3/59 (5.1%) 1/58 (1.7%)
    Oral candidiasis 3/59 (5.1%) 1/58 (1.7%)
    Paronychia 3/59 (5.1%) 1/58 (1.7%)
    Skin infection 3/59 (5.1%) 2/58 (3.4%)
    Ear infection 4/59 (6.8%) 2/58 (3.4%)
    Influenza 4/59 (6.8%) 1/58 (1.7%)
    Cellulitis 5/59 (8.5%) 2/58 (3.4%)
    Herpes zoster 5/59 (8.5%) 1/58 (1.7%)
    Bronchitis 6/59 (10.2%) 2/58 (3.4%)
    Nasopharyngitis 6/59 (10.2%) 5/58 (8.6%)
    Urinary tract infection 6/59 (10.2%) 8/58 (13.8%)
    Pneumonia 11/59 (18.6%) 5/58 (8.6%)
    Sinusitis 15/59 (25.4%) 11/58 (19%)
    Upper respiratory tract infection 18/59 (30.5%) 16/58 (27.6%)
    Injury, poisoning and procedural complications
    Procedural pain 3/59 (5.1%) 1/58 (1.7%)
    Arthropod bite 4/59 (6.8%) 3/58 (5.2%)
    Skin abrasion 4/59 (6.8%) 2/58 (3.4%)
    Fall 6/59 (10.2%) 8/58 (13.8%)
    Contusion 16/59 (27.1%) 17/58 (29.3%)
    Infusion related reaction 16/59 (27.1%) 0/58 (0%)
    Investigations
    Blood bilirubin increased 1/59 (1.7%) 5/58 (8.6%)
    Alanine aminotransferase increased 2/59 (3.4%) 3/58 (5.2%)
    Aspartate aminotransferase increased 2/59 (3.4%) 3/58 (5.2%)
    Lymphocyte count increased 3/59 (5.1%) 2/58 (3.4%)
    Weight decreased 4/59 (6.8%) 3/58 (5.2%)
    Blood uric acid increased 5/59 (8.5%) 1/58 (1.7%)
    Blood creatinine increased 7/59 (11.9%) 2/58 (3.4%)
    Platelet count decreased 8/59 (13.6%) 8/58 (13.8%)
    Neutrophil count decreased 9/59 (15.3%) 5/58 (8.6%)
    Metabolism and nutrition disorders
    Hyperkalaemia 2/59 (3.4%) 3/58 (5.2%)
    Dehydration 3/59 (5.1%) 3/58 (5.2%)
    Hyperglycaemia 3/59 (5.1%) 4/58 (6.9%)
    Hypophosphataemia 3/59 (5.1%) 2/58 (3.4%)
    Hypokalaemia 4/59 (6.8%) 8/58 (13.8%)
    Hyperuricaemia 5/59 (8.5%) 2/58 (3.4%)
    Hypomagnesaemia 7/59 (11.9%) 6/58 (10.3%)
    Decreased appetite 10/59 (16.9%) 7/58 (12.1%)
    Musculoskeletal and connective tissue disorders
    Muscular weakness 2/59 (3.4%) 3/58 (5.2%)
    Neck pain 2/59 (3.4%) 5/58 (8.6%)
    Flank pain 3/59 (5.1%) 2/58 (3.4%)
    Groin pain 4/59 (6.8%) 1/58 (1.7%)
    Musculoskeletal chest pain 6/59 (10.2%) 1/58 (1.7%)
    Pain in extremity 7/59 (11.9%) 7/58 (12.1%)
    Myalgia 8/59 (13.6%) 14/58 (24.1%)
    Muscle spasms 10/59 (16.9%) 8/58 (13.8%)
    Back pain 12/59 (20.3%) 10/58 (17.2%)
    Arthralgia 18/59 (30.5%) 13/58 (22.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/59 (1.7%) 3/58 (5.2%)
    Nervous system disorders
    Neuropathy peripheral 0/59 (0%) 3/58 (5.2%)
    Paraesthesia 5/59 (8.5%) 2/58 (3.4%)
    Dysgeusia 6/59 (10.2%) 3/58 (5.2%)
    Dizziness 15/59 (25.4%) 15/58 (25.9%)
    Headache 18/59 (30.5%) 17/58 (29.3%)
    Psychiatric disorders
    Confusional state 0/59 (0%) 6/58 (10.3%)
    Depression 6/59 (10.2%) 5/58 (8.6%)
    Anxiety 7/59 (11.9%) 8/58 (13.8%)
    Insomnia 17/59 (28.8%) 10/58 (17.2%)
    Renal and urinary disorders
    Urinary retention 3/59 (5.1%) 3/58 (5.2%)
    Haematuria 4/59 (6.8%) 4/58 (6.9%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/59 (1.7%) 3/58 (5.2%)
    Bronchiectasis 3/59 (5.1%) 0/58 (0%)
    Rhinorrhoea 3/59 (5.1%) 4/58 (6.9%)
    Sinus congestion 3/59 (5.1%) 3/58 (5.2%)
    Wheezing 3/59 (5.1%) 2/58 (3.4%)
    Haemoptysis 4/59 (6.8%) 1/58 (1.7%)
    Hiccups 4/59 (6.8%) 3/58 (5.2%)
    Pneumonitis 4/59 (6.8%) 1/58 (1.7%)
    Dysphonia 5/59 (8.5%) 0/58 (0%)
    Dyspnoea exertional 6/59 (10.2%) 2/58 (3.4%)
    Nasal congestion 7/59 (11.9%) 5/58 (8.6%)
    Rhinitis allergic 7/59 (11.9%) 2/58 (3.4%)
    Epistaxis 8/59 (13.6%) 8/58 (13.8%)
    Productive cough 9/59 (15.3%) 8/58 (13.8%)
    Upper-airway cough syndrome 9/59 (15.3%) 4/58 (6.9%)
    Oropharyngeal pain 11/59 (18.6%) 6/58 (10.3%)
    Dyspnoea 13/59 (22%) 11/58 (19%)
    Cough 25/59 (42.4%) 18/58 (31%)
    Skin and subcutaneous tissue disorders
    Skin fissures 0/59 (0%) 3/58 (5.2%)
    Erythema 2/59 (3.4%) 3/58 (5.2%)
    Dermatitis acneiform 3/59 (5.1%) 3/58 (5.2%)
    Hyperhidrosis 3/59 (5.1%) 5/58 (8.6%)
    Dry skin 4/59 (6.8%) 8/58 (13.8%)
    Onychoclasis 4/59 (6.8%) 3/58 (5.2%)
    Petechiae 4/59 (6.8%) 4/58 (6.9%)
    Ecchymosis 5/59 (8.5%) 5/58 (8.6%)
    Night sweats 5/59 (8.5%) 4/58 (6.9%)
    Pruritus 5/59 (8.5%) 5/58 (8.6%)
    Skin lesion 5/59 (8.5%) 4/58 (6.9%)
    Rash 8/59 (13.6%) 7/58 (12.1%)
    Rash maculo-papular 10/59 (16.9%) 2/58 (3.4%)
    Vascular disorders
    Flushing 3/59 (5.1%) 1/58 (1.7%)
    Hot flush 4/59 (6.8%) 3/58 (5.2%)
    Hypertension 8/59 (13.6%) 6/58 (10.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    TG Therapeutics has the right to review all proposed abstracts, manuscripts or presentations prior to submission for publication; however, the terms and conditions, including timing for review, of TG Therapeutics' agreements with its investigators may vary. Any single-site publications will be postponed until publication of data from the entire clinical trial (pooled from all sites). An investigator may not disclose TG Therapeutics confidential information other than study results.

    Results Point of Contact

    Name/Title TG Therapeutics Clinical Support Team
    Organization TG Therapeutics
    Phone 1-877-575-8489
    Email clinicalsupport@tgtxinc.com
    Responsible Party:
    TG Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02301156
    Other Study ID Numbers:
    • UTX-IB-301
    First Posted:
    Nov 25, 2014
    Last Update Posted:
    May 20, 2022
    Last Verified:
    Apr 1, 2022