Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
Sponsor
Pharmacyclics LLC. (Industry)
Overall Status
Completed
CT.gov ID
NCT01980654
Collaborator
(none)
80
12
2
47
6.7
0.1
Study Details
Study Description
Brief Summary
This is an open-label, Phase 2 study designed to assess the efficacy and safety of ibrutinib combined with rituximab in previously untreated subjects with Follicular Lymphoma (FL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is an open-label, Phase 2 study designed to assess the efficacy and safety of ibrutinib combined with rituximab in previously untreated subjects with FL.
There are two study treatment arms.
Subjects enrolled into main study treatment arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Subjects enrolled into the exploratory study treatment arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Study Design
Study Type:
Interventional
Actual Enrollment
:
80 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
Study Start Date
:
Dec 1, 2013
Actual Primary Completion Date
:
Nov 1, 2017
Actual Study Completion Date
:
Nov 1, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Main Study Arm 1 Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. |
Drug: Ibrutinib
All subjects will receive 560 mg of Ibrutinib orally.
Other Names:
Drug: rituximab
All subjects will receive rituximab 375 mg/m2 intravenously
Other Names:
|
| Experimental: Exploratory Study Arm 2 Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. |
Drug: Ibrutinib
All subjects will receive 560 mg of Ibrutinib orally.
Other Names:
Drug: rituximab
All subjects will receive rituximab 375 mg/m2 intravenously
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR) [Subjects in Arm 1 will have imaging assessments every 12 weeks for the first 8 assessments, then every 24 weeks. Subjects in Arm 2 will have imaging assessments starting at week 9, then every 12 weeks for 8 assessments, then every 24 weeks.]
Number of subjects achieving the best overall responses of CR or PR prior to the initiation of the next line of antineoplastic therapy as assessed by investigator per the Cheson et al, 2007 criteria. Target lesions are measured by CT, unless MRI is used as the assessment modality for lesions in anatomical locations not amenable to CT. CR is defined as the disappearance of all evidence of disease. PR is defined as >=50% decrease in the sum of the product of the diameters of up to 6 largest dominant masses.
Secondary Outcome Measures
- Duration of Response (DOR) [Up to 45 months]
DOR is defined as the interval between the date of the first documented response (CR, PR) and the date of the first documented evidence of progressive disease (PD) or death. DOR will be analyzed for the subjects who achieve an overall response during the duration of study.
- Progression Free Survival (PFS) [Up to 45 months]
PFS is defined as the time interval between the date of the first dose and the date of the earliest occurrence of PD or death due to any cause, whichever occurs first. PD is characterized by any new lesion or increase by >=50% of previously involved sites from nadir.
- Overall Survival (OS) [Up to 45 months]
Subjects will be followed for survival information up to three years after the last dose of study treatment, until new treatment or death, whichever occurs first. OS is defined as the duration of time from the date of the first dose to the date of death from any cause.
- Number of Participants With Treatment-emergent Adverse Events [Up to 45 months]
Frequency, severity, and relatedness of treatment-emergent adverse events (AEs) Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion criteria:
-
Histologically documented FL (Grade 1, 2 and 3A)
-
Not previously treated with prior anti-cancer therapy for FL
-
Stage II, III or IV disease
-
At least one measurable lesion ≥ 2 cm in longest diameter by CT and/or MRI scan
-
Men and women ≥ 18 years of age
-
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
Key Exclusion criteria:
-
Medically apparent central nervous system lymphoma or leptomeningeal disease
-
FL with evidence of large cell transformation
-
Any prior history of other hematologic malignancy besides FL or myelodysplasia
-
History of other malignancies, except
-
Malignancy treated with curative intent and with no known active disease present for ≥5 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
-
Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease.
-
Adequately treated carcinoma in situ without evidence of disease.
-
Currently active, clinically significant cardiovascular disease or myocardial infarction within 6 months of screening
-
Known anaphylaxis or Immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab (Rituxan®)
-
Requires anti-coagulation with warfarin or a vitamin K antagonist.
-
Requires treatment with strong cytochrome P450 (CYP) 3A inhibitors.
-
Known bleeding diathesis or hemophilia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Providence Saint Joseph Medical Center | Burbank | California | United States | 91505 |
| 2 | City of Hope | Duarte | California | United States | 91010 |
| 3 | UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 4 | Stanford University, Stanford Care Center | Stanford | California | United States | 94305 |
| 5 | Southeastern Regional Medical Center | Newnan | Georgia | United States | 30265 |
| 6 | Community Health Network Community Regional Cancer Center North | Indianapolis | Indiana | United States | 46256 |
| 7 | Comprehensive Cancer Centers of Nevada | Henderson | Nevada | United States | 89074 |
| 8 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
| 9 | Weill Cornell Medical College New York-Presbyterian Hospital | New York | New York | United States | 10065 |
| 10 | Mid-Ohio Oncology/ Hematology Inc | Columbus | Ohio | United States | 43219 |
| 11 | Tennessee Oncology, PLLC The Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 12 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Pharmacyclics LLC.
Investigators
- Study Director: Jutta K. Neuenburg, MD, PhD, Pharmacyclics LLC.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
NCT01980654
Other Study ID Numbers:
- PCYC-1125-CA
First Posted:
Nov 11, 2013
Last Update Posted:
Apr 16, 2019
Last Verified:
Mar 1, 2019
Keywords provided by Pharmacyclics LLC.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 |
|---|---|---|
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously |
| Period Title: Overall Study | ||
| STARTED | 60 | 20 |
| COMPLETED | 60 | 20 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 | Total |
|---|---|---|---|
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Total of all reporting groups |
| Overall Participants | 60 | 20 | 80 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
42
70%
|
12
60%
|
54
67.5%
|
| >=65 years |
18
30%
|
8
40%
|
26
32.5%
|
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
58.0
|
55.0
|
58.0
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
32
53.3%
|
8
40%
|
40
50%
|
| Male |
28
46.7%
|
12
60%
|
40
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
3
5%
|
3
15%
|
6
7.5%
|
| Not Hispanic or Latino |
57
95%
|
17
85%
|
74
92.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
1.7%
|
1
5%
|
2
2.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
3.3%
|
1
5%
|
3
3.8%
|
| White |
56
93.3%
|
18
90%
|
74
92.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
1.7%
|
0
0%
|
1
1.3%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
60
100%
|
20
100%
|
80
100%
|
| Baseline B-Symptoms (Count of Participants) | |||
| B-Symptoms present prior to first dose |
4
6.7%
|
0
0%
|
4
5%
|
| B-Symptoms absent |
56
93.3%
|
20
100%
|
76
95%
|
| Baseline Eastern Cooperative Oncology Group (ECOG) Score (Count of Participants) | |||
| Baseline ECOG Score = 0 |
47
78.3%
|
12
60%
|
59
73.8%
|
| Baseline ECOG Score = 1 |
13
21.7%
|
8
40%
|
21
26.3%
|
Outcome Measures
| Title | Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR) |
|---|---|
| Description | Number of subjects achieving the best overall responses of CR or PR prior to the initiation of the next line of antineoplastic therapy as assessed by investigator per the Cheson et al, 2007 criteria. Target lesions are measured by CT, unless MRI is used as the assessment modality for lesions in anatomical locations not amenable to CT. CR is defined as the disappearance of all evidence of disease. PR is defined as >=50% decrease in the sum of the product of the diameters of up to 6 largest dominant masses. |
| Time Frame | Subjects in Arm 1 will have imaging assessments every 12 weeks for the first 8 assessments, then every 24 weeks. Subjects in Arm 2 will have imaging assessments starting at week 9, then every 12 weeks for 8 assessments, then every 24 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 |
|---|---|---|
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously |
| Measure Participants | 60 | 20 |
| Count of Participants [Participants] |
51
85%
|
15
75%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR is defined as the interval between the date of the first documented response (CR, PR) and the date of the first documented evidence of progressive disease (PD) or death. DOR will be analyzed for the subjects who achieve an overall response during the duration of study. |
| Time Frame | Up to 45 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 |
|---|---|---|
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously |
| Measure Participants | 51 | 15 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time interval between the date of the first dose and the date of the earliest occurrence of PD or death due to any cause, whichever occurs first. PD is characterized by any new lesion or increase by >=50% of previously involved sites from nadir. |
| Time Frame | Up to 45 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 |
|---|---|---|
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously |
| Measure Participants | 60 | 20 |
| Median (95% Confidence Interval) [months] |
41.922
|
NA
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Subjects will be followed for survival information up to three years after the last dose of study treatment, until new treatment or death, whichever occurs first. OS is defined as the duration of time from the date of the first dose to the date of death from any cause. |
| Time Frame | Up to 45 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 |
|---|---|---|
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously |
| Measure Participants | 60 | 20 |
| Median (95% Confidence Interval) [months] |
41.922
|
NA
|
| Title | Number of Participants With Treatment-emergent Adverse Events |
|---|---|
| Description | Frequency, severity, and relatedness of treatment-emergent adverse events (AEs) Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions |
| Time Frame | Up to 45 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 |
|---|---|---|
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously |
| Measure Participants | 60 | 20 |
| Subjects with any treatment-emergent AE |
60
100%
|
20
100%
|
| Subjects with any treatment-emergent AE Grade >=3 |
39
65%
|
14
70%
|
| Subjects with any treatment-related AE |
59
98.3%
|
20
100%
|
| Subjects with any treatment-related AE Grade >=3 |
29
48.3%
|
14
70%
|
| Subjects with any Ibrutinib-related AE |
57
95%
|
20
100%
|
| Subjects with any Ibrutinib-related AE Grade >=3 |
29
48.3%
|
14
70%
|
| Subjects with any Rituximab-related AE |
50
83.3%
|
17
85%
|
| Subjects with any Rituximab-related AE Grade >=3 |
11
18.3%
|
7
35%
|
| TEAE leading to ibrutinib dose reduction |
9
15%
|
5
25%
|
| TEAE Grade >=3 leading to Ibrutinib dose reduction |
6
10%
|
4
20%
|
| TEAE leading to witholding Rituximab |
1
1.7%
|
1
5%
|
| TEAE Grade >=3 leading to witholding Rituximab |
1
1.7%
|
1
5%
|
| TEAE leading to discontinuation of Ibrutinib |
14
23.3%
|
2
10%
|
| TEAE Grade >=3 leading to discontinuation of Ibrut |
11
18.3%
|
1
5%
|
| TEAE leading to discontinuation of Rituximab |
0
0%
|
0
0%
|
| TEAE Grade >=3 leading to discontinuation of Ritux |
0
0%
|
0
0%
|
| Subjects with any TE Serious Adverse Event (SAE) |
14
23.3%
|
6
30%
|
| Subjects with any TE SAE Grade >=3 |
13
21.7%
|
5
25%
|
| Ibrutinib-related SAEs |
6
10%
|
4
20%
|
| Ibrutinib-related SAEs Grade >=3 |
6
10%
|
4
20%
|
| Rituximab-related SAEs |
2
3.3%
|
2
10%
|
| Rituximab-related SAEs Grade >=3 |
2
3.3%
|
2
10%
|
Adverse Events
| Time Frame | 3 years, 9 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Main Study Arm 1 | Exploratory Study Arm 2 | ||
| Arm/Group Description | Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity. Ibrutinib: All subjects will receive 560 mg of Ibrutinib orally. rituximab: All subjects will receive rituximab 375 mg/m2 intravenously | ||
All Cause Mortality |
||||
| Main Study Arm 1 | Exploratory Study Arm 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/60 (6.7%) | 0/20 (0%) | ||
Serious Adverse Events |
||||
| Main Study Arm 1 | Exploratory Study Arm 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/60 (23.3%) | 6/20 (30%) | ||
| Blood and lymphatic system disorders | ||||
| Eosinophilia | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Febrile neutropenia | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Cardiac disorders | ||||
| Atrial fibrillation | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Cardiac failure | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Pericardial effusion | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Ventricular tachycardia | 1/60 (1.7%) | 2 | 0/20 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 0/60 (0%) | 0 | 2/20 (10%) | 2 |
| Abdominal pain | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Oesophageal achalasia | 1/60 (1.7%) | 2 | 0/20 (0%) | 0 |
| Rectal haemorrhage | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| General disorders | ||||
| Pyrexia | 2/60 (3.3%) | 2 | 3/20 (15%) | 3 |
| Death | 2/60 (3.3%) | 2 | 0/20 (0%) | 0 |
| Chest pain | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Non-cardiac chest pain | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Infections and infestations | ||||
| Pneumonia | 2/60 (3.3%) | 3 | 2/20 (10%) | 2 |
| Urinary tract infection | 1/60 (1.7%) | 2 | 1/20 (5%) | 1 |
| Bronchitis | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Clostridium difficile colitis | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Influenza | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Sepsis | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Hyponatraemia | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthritis | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Muscular weakness | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Musculoskeletal pain | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Myalgia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Tendonitis | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Fallopian tube cancer | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Lung adenocarcinoma | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Nervous system disorders | ||||
| Cerebral artery stenosis | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Headache | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Transient ischaemic attack | 1/60 (1.7%) | 2 | 0/20 (0%) | 0 |
| Vascular encephalopathy | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/60 (1.7%) | 2 | 0/20 (0%) | 0 |
| Cough | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Dyspnoea | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Pleural effusion | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Pulmonary oedema | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
| Respiratory failure | 1/60 (1.7%) | 1 | 0/20 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Main Study Arm 1 | Exploratory Study Arm 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 60/60 (100%) | 20/20 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 9/60 (15%) | 11 | 3/20 (15%) | 3 |
| Thrombocytopenia | 8/60 (13.3%) | 13 | 2/20 (10%) | 2 |
| Increased tendency to bruise | 4/60 (6.7%) | 4 | 1/20 (5%) | 1 |
| Anaemia | 3/60 (5%) | 4 | 0/20 (0%) | 0 |
| Cardiac disorders | ||||
| Atrial fibrillation | 5/60 (8.3%) | 5 | 0/20 (0%) | 0 |
| Cardiac flutter | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Sinus bradycardia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Tachycardia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Congenital, familial and genetic disorders | ||||
| Gilbert's syndrome | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Ear and labyrinth disorders | ||||
| Ear pain | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Tinnitus | 0/60 (0%) | 0 | 2/20 (10%) | 2 |
| Conductive deafness | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Ear haemorrhage | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Endocrine disorders | ||||
| Hypothyroidism | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Eye disorders | ||||
| Dry eye | 15/60 (25%) | 24 | 4/20 (20%) | 7 |
| Vision blurred | 8/60 (13.3%) | 13 | 6/20 (30%) | 10 |
| Lacrimation increased | 3/60 (5%) | 4 | 6/20 (30%) | 8 |
| Eye irritation | 4/60 (6.7%) | 4 | 1/20 (5%) | 2 |
| Eye pruritus | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Diplopia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 34/60 (56.7%) | 78 | 12/20 (60%) | 30 |
| Nausea | 29/60 (48.3%) | 68 | 10/20 (50%) | 22 |
| Constipation | 16/60 (26.7%) | 32 | 6/20 (30%) | 12 |
| Vomiting | 16/60 (26.7%) | 30 | 6/20 (30%) | 7 |
| Stomatitis | 10/60 (16.7%) | 33 | 11/20 (55%) | 35 |
| Abdominal pain | 12/60 (20%) | 13 | 4/20 (20%) | 4 |
| Dyspepsia | 8/60 (13.3%) | 10 | 3/20 (15%) | 3 |
| Dry mouth | 4/60 (6.7%) | 4 | 4/20 (20%) | 4 |
| Flatulence | 5/60 (8.3%) | 5 | 1/20 (5%) | 1 |
| Gastrooesophageal reflux disease | 5/60 (8.3%) | 5 | 1/20 (5%) | 1 |
| Haemorrhoids | 2/60 (3.3%) | 3 | 3/20 (15%) | 3 |
| Abdominal pain upper | 4/60 (6.7%) | 6 | 0/20 (0%) | 0 |
| Gingival bleeding | 4/60 (6.7%) | 6 | 0/20 (0%) | 0 |
| Abdominal discomfort | 2/60 (3.3%) | 2 | 1/20 (5%) | 11 |
| Abdominal distension | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Haematochezia | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Chapped lips | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Barrett's oesophagus | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Haemorrhoidal haemorrhage | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Hypoaesthesia oral | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Lip discolouration | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Lip ulceration | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Toothache | 0/60 (0%) | 0 | 1/20 (5%) | 5 |
| General disorders | ||||
| Fatigue | 41/60 (68.3%) | 108 | 15/20 (75%) | 30 |
| Pyrexia | 15/60 (25%) | 20 | 4/20 (20%) | 5 |
| Chills | 10/60 (16.7%) | 12 | 1/20 (5%) | 1 |
| Oedema peripheral | 9/60 (15%) | 13 | 1/20 (5%) | 1 |
| Peripheral swelling | 5/60 (8.3%) | 7 | 4/20 (20%) | 9 |
| Chest pain | 4/60 (6.7%) | 4 | 2/20 (10%) | 2 |
| Pain | 4/60 (6.7%) | 4 | 2/20 (10%) | 2 |
| Chest discomfort | 4/60 (6.7%) | 4 | 1/20 (5%) | 1 |
| Swelling | 2/60 (3.3%) | 3 | 2/20 (10%) | 4 |
| Malaise | 3/60 (5%) | 4 | 0/20 (0%) | 0 |
| Unevaluable event | 0/60 (0%) | 0 | 2/20 (10%) | 2 |
| Feeling hot | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Gait disturbance | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Generalised oedema | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 3/60 (5%) | 5 | 2/20 (10%) | 2 |
| Hepatic function abnormal | 2/60 (3.3%) | 4 | 1/20 (5%) | 7 |
| Immune system disorders | ||||
| Drug hypersensitivity | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Infections and infestations | ||||
| Upper respiratory tract infection | 13/60 (21.7%) | 16 | 7/20 (35%) | 12 |
| Urinary tract infection | 13/60 (21.7%) | 28 | 5/20 (25%) | 7 |
| Sinusitis | 7/60 (11.7%) | 8 | 5/20 (25%) | 10 |
| Conjunctivitis | 4/60 (6.7%) | 4 | 1/20 (5%) | 1 |
| Folliculitis | 2/60 (3.3%) | 3 | 2/20 (10%) | 2 |
| Herpes zoster | 4/60 (6.7%) | 5 | 0/20 (0%) | 0 |
| Onychomycosis | 2/60 (3.3%) | 2 | 2/20 (10%) | 2 |
| Tooth infection | 3/60 (5%) | 3 | 1/20 (5%) | 1 |
| Cystitis | 0/60 (0%) | 0 | 3/20 (15%) | 5 |
| Influenza | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Oral herpes | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Pneumonia | 3/60 (5%) | 5 | 0/20 (0%) | 0 |
| Viral upper respiratory tract infection | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Clostridium difficile infection | 0/60 (0%) | 0 | 2/20 (10%) | 2 |
| Dacryocanaliculitis | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Ear infection | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Localised infection | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Pharyngitis | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Bacterial vaginosis | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Cellulitis | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Eye infection | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Prostate infection | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Bronchitis | 7/60 (11.7%) | 9 | 0/20 (0%) | 0 |
| Respiratory tract infection viral | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Rhinitis | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Streptococcal infection | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Tinea cruris | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Tinea pedis | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Vulvovaginal mycotic infection | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Wound infection staphylococcal | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 14/60 (23.3%) | 16 | 1/20 (5%) | 1 |
| Contusion | 5/60 (8.3%) | 8 | 2/20 (10%) | 2 |
| Fall | 3/60 (5%) | 3 | 1/20 (5%) | 1 |
| Laceration | 3/60 (5%) | 4 | 1/20 (5%) | 1 |
| Skin abrasion | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Arthropod sting | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Road traffic accident | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Investigations | ||||
| Aspartate aminotransferase increased | 4/60 (6.7%) | 4 | 1/20 (5%) | 2 |
| Alanine aminotransferase increased | 3/60 (5%) | 4 | 1/20 (5%) | 3 |
| Blood bilirubin increased | 1/60 (1.7%) | 1 | 1/20 (5%) | 2 |
| Blood pressure increased | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Low density lipoprotein increased | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| White blood cell count increased | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Metabolism and nutrition disorders | ||||
| Hypomagnesaemia | 6/60 (10%) | 7 | 4/20 (20%) | 4 |
| Decreased appetite | 7/60 (11.7%) | 9 | 1/20 (5%) | 1 |
| Hyperuricaemia | 5/60 (8.3%) | 5 | 0/20 (0%) | 0 |
| Dehydration | 3/60 (5%) | 3 | 1/20 (5%) | 1 |
| Hyperglycaemia | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Hyperkalaemia | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Hypoglycaemia | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Abnormal loss of weight | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Hypernatraemia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Polydipsia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 20/60 (33.3%) | 38 | 9/20 (45%) | 20 |
| Arthralgia | 20/60 (33.3%) | 27 | 3/20 (15%) | 5 |
| Muscle spasms | 16/60 (26.7%) | 22 | 5/20 (25%) | 8 |
| Pain in extremity | 8/60 (13.3%) | 13 | 2/20 (10%) | 2 |
| Back pain | 7/60 (11.7%) | 10 | 2/20 (10%) | 3 |
| Joint swelling | 4/60 (6.7%) | 8 | 1/20 (5%) | 1 |
| Arthritis | 3/60 (5%) | 5 | 0/20 (0%) | 0 |
| Neck pain | 1/60 (1.7%) | 1 | 2/20 (10%) | 2 |
| Musculoskeletal pain | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Musculoskeletal stiffness | 1/60 (1.7%) | 1 | 1/20 (5%) | 2 |
| Tendonitis | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Flank pain | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Seborrhoeic keratosis | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Nervous system disorders | ||||
| Headache | 19/60 (31.7%) | 27 | 5/20 (25%) | 10 |
| Dizziness | 13/60 (21.7%) | 18 | 9/20 (45%) | 19 |
| Paraesthesia | 9/60 (15%) | 20 | 8/20 (40%) | 19 |
| Memory impairment | 9/60 (15%) | 13 | 5/20 (25%) | 9 |
| Hypoaesthesia | 3/60 (5%) | 3 | 1/20 (5%) | 2 |
| Cognitive disorder | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Peripheral sensory neuropathy | 3/60 (5%) | 4 | 0/20 (0%) | 0 |
| Tremor | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Migraine | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Restless legs syndrome | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Dyskinesia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Syncope | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Psychiatric disorders | ||||
| Anxiety | 9/60 (15%) | 9 | 0/20 (0%) | 0 |
| Insomnia | 8/60 (13.3%) | 10 | 1/20 (5%) | 1 |
| Depression | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Renal and urinary disorders | ||||
| Haematuria | 4/60 (6.7%) | 4 | 0/20 (0%) | 0 |
| Pollakiuria | 2/60 (3.3%) | 2 | 2/20 (10%) | 2 |
| Dysuria | 1/60 (1.7%) | 2 | 1/20 (5%) | 1 |
| Hydronephrosis | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Nocturia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Polyuria | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Reproductive system and breast disorders | ||||
| Vulvovaginal dryness | 0/60 (0%) | 0 | 2/20 (10%) | 2 |
| Benign prostatic hyperplasia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Dyspareunia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Vulvovaginal erythema | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Vulvovaginal pain | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 20/60 (33.3%) | 26 | 6/20 (30%) | 9 |
| Dyspnoea | 12/60 (20%) | 23 | 4/20 (20%) | 8 |
| Oropharyngeal pain | 10/60 (16.7%) | 11 | 5/20 (25%) | 6 |
| Nasal congestion | 5/60 (8.3%) | 9 | 2/20 (10%) | 4 |
| Epistaxis | 6/60 (10%) | 9 | 0/20 (0%) | 0 |
| Sinus congestion | 3/60 (5%) | 4 | 2/20 (10%) | 2 |
| Rhinorrhoea | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Throat irritation | 0/60 (0%) | 0 | 2/20 (10%) | 2 |
| Dysphonia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Nasal discomfort | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Pharyngeal oedema | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Rash maculo-papular | 18/60 (30%) | 32 | 8/20 (40%) | 10 |
| Dry skin | 7/60 (11.7%) | 7 | 3/20 (15%) | 3 |
| Onychoclasis | 8/60 (13.3%) | 9 | 1/20 (5%) | 1 |
| Pruritus | 7/60 (11.7%) | 12 | 2/20 (10%) | 2 |
| Rash erythematous | 7/60 (11.7%) | 9 | 1/20 (5%) | 1 |
| Petechiae | 6/60 (10%) | 13 | 0/20 (0%) | 0 |
| Ecchymosis | 4/60 (6.7%) | 6 | 1/20 (5%) | 1 |
| Nail disorder | 3/60 (5%) | 3 | 1/20 (5%) | 1 |
| Night sweats | 4/60 (6.7%) | 4 | 0/20 (0%) | 0 |
| Rash | 2/60 (3.3%) | 3 | 2/20 (10%) | 3 |
| Skin fissures | 2/60 (3.3%) | 2 | 2/20 (10%) | 3 |
| Alopecia | 3/60 (5%) | 3 | 0/20 (0%) | 0 |
| Eczema | 2/60 (3.3%) | 3 | 1/20 (5%) | 1 |
| Erythema | 2/60 (3.3%) | 3 | 1/20 (5%) | 1 |
| Ingrowing nail | 2/60 (3.3%) | 2 | 1/20 (5%) | 1 |
| Rash macular | 2/60 (3.3%) | 3 | 1/20 (5%) | 2 |
| Acne | 1/60 (1.7%) | 1 | 1/20 (5%) | 2 |
| Actinic keratosis | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Dermatitis acneiform | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Rosacea | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Skin hyperpigmentation | 1/60 (1.7%) | 1 | 1/20 (5%) | 1 |
| Dermatitis allergic | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Eczema nummular | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Exfoliative rash | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Koilonychia | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Nail discolouration | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Pyoderma gangrenosum | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Scab | 0/60 (0%) | 0 | 1/20 (5%) | 1 |
| Vascular disorders | ||||
| Hypertension | 10/60 (16.7%) | 12 | 2/20 (10%) | 3 |
| Hot flush | 4/60 (6.7%) | 4 | 0/20 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Dr. Jutta Neuenburg |
|---|---|
| Organization | Pharmacyclics |
| Phone | 408-215-3735 |
| jneuenburg@pcyc.com |
Responsible Party:
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
NCT01980654
Other Study ID Numbers:
- PCYC-1125-CA
First Posted:
Nov 11, 2013
Last Update Posted:
Apr 16, 2019
Last Verified:
Mar 1, 2019