GENUINE: Ublituximab in Combination With Ibrutinib Versus Ibrutinib Alone in Participants With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL)
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
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:
Drug: Ibrutinib
Administered orally
Other Names:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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.- UTX-IB-301
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
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. |
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. |
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. |
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. |
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. |
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. |
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
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 |
clinicalsupport@tgtxinc.com |
- UTX-IB-301