Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Sponsor
Pharmacyclics LLC. (Industry)
Overall Status
Completed
CT.gov ID
NCT02142049
Collaborator
Celgene Corporation (Industry)
35
10
5
39
3.5
0.1
Study Details
Study Description
Brief Summary
This is a Phase 1b/2, open-label, non-randomized multicenter study to assess the safety and efficacy of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
This is a Phase 1b, open-label, non-randomized multicenter study conducted in 2 parts. Part 1, will determine the MTD of the combination of ibrutinib, lenalidomide and DA-EPOCH-R in subjects with DLBCL.
Ibrutinib will be administered at a fixed dose of 560 mg and lenalidomide will be dose-escalated. DA-EPOCH-R will be given at standard doses.
For Part 2, the MTD determined in Part 1 will be the dose used for all subjects. If no MTD is identified, then subjects in Part 2 will be treated with the maximum administered doses (MAD, treatment doses from dose Level 4).
The primary objective for Part 2 is to determine the ORR of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with ABC DLBCL as analyzed by gene expression profiling when treated at recommended phase 2 dose (RP2D).
Study Design
Study Type:
Interventional
Actual Enrollment
:
35 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Study of Ibrutinib and Lenalidomide in Combination With DA-EPOCH-R in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Study Start Date
:
May 1, 2014
Actual Primary Completion Date
:
Aug 1, 2017
Actual Study Completion Date
:
Aug 1, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Dose Level 1 Ibrutinib 560 mg PO + DA-EPOCH-R |
Drug: Ibrutinib
Ibrutinib
Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
|
| Experimental: Part 1: Dose Level 2 Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R |
Drug: Ibrutinib
Ibrutinib
Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Drug: Lenalidomide
Lenalidomide
|
| Experimental: Part 1: Dose Level 3 Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R |
Drug: Ibrutinib
Ibrutinib
Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Drug: Lenalidomide
Lenalidomide
|
| Experimental: Part 1: Dose Level 4 Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R |
Drug: Ibrutinib
Ibrutinib
Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Drug: Lenalidomide
Lenalidomide
|
| Experimental: Part 2: RP2D Recommended Phase 2 Dose(RP2D): Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R |
Drug: Ibrutinib
Ibrutinib
Drug: DA-EPOCH-R
Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim
Drug: Lenalidomide
Lenalidomide
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability [1 year after last subjects received the first dose]
Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R
- Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR [1 year after last subjects received the first dose]
Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator.
Secondary Outcome Measures
- Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy [1 year after last subjects received the first dose]
Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator.
- Number of Subjects With Adverse Events as a Measure of Safety and Tolerability [1 year after last subjects received the first dose]
Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported.
- Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy [From initial dose date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose, up to 36 months at the most.]
Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause. OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology.
- Duration of Response (DOR) [From initial response date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose.]
Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Major inclusion criteria:
-
Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
-
Pathologically confirmed relapsed/refractory DLBCL
-
Subjects must have ≥1 measurable disease site on CT scan (≥ 1.5 cm in longest dimension).
-
Adequate hepatic and renal function:
-
AST or ALT ≤2.5 x ULN
-
Serum Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥60 mL/min/1.73
-
Bilirubin ≤1.5 x ULN
-
Adequate hematologic function:
-
ANC >1,000 cells/mm3
-
Platelets ≥75,000 cells/mm3
-
Hemoglobin ≥8.0 g/dL
-
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be ≤1.5 x the upper limit of the normal range (ULN)
-
Must be registered into the Revlimid REMS™program and be willing to comply with the requirements of Revlimid REMS™.
Major Exclusion Criteria:
-
Known central nervous system lymphoma
-
Any chemotherapy, external beam radiation therapy, or anti-cancer antibodies within 2 weeks
-
Radio- or toxin-immunoconjugates within 10 weeks
-
Prior allogenetic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | SITE-1 | Duarte | California | United States | 91010 |
| 2 | SITE-2 | Los Angeles | California | United States | 90095 |
| 3 | SITE-10 | Orange | California | United States | 92868 |
| 4 | SITE-3 | Chicago | Illinois | United States | 60612 |
| 5 | SITE-5 | Baltimore | Maryland | United States | 21201 |
| 6 | SITE-6 | Bethesda | Maryland | United States | 20892 |
| 7 | SITE-4 | Ann Arbor | Michigan | United States | 48109 |
| 8 | SITE-8 | Albuquerque | New Mexico | United States | 87106 |
| 9 | SITE-9 | Stony Brook | New York | United States | 11794 |
| 10 | SITE-7 | Charleston | South Carolina | United States | 29425 |
Sponsors and Collaborators
- Pharmacyclics LLC.
- Celgene Corporation
Investigators
- Study Director: Jutta Neuenburg, MD, Pharmacyclics LLC (An AbbVie Company)
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
NCT02142049
Other Study ID Numbers:
- PCYC-1124-CA
First Posted:
May 20, 2014
Last Update Posted:
Feb 5, 2019
Last Verified:
May 1, 2018
Keywords provided by Pharmacyclics LLC.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | Part 2: RP2D |
|---|---|---|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg PO + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim |
| Period Title: Overall Study | |||||
| STARTED | 3 | 3 | 3 | 6 | 20 |
| COMPLETED | 3 | 3 | 3 | 6 | 20 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | Part 2: RP2D | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg PO + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 6 | 20 | 35 |
| Age (Count of Participants) | ||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
1
33.3%
|
3
100%
|
1
33.3%
|
6
100%
|
11
55%
|
22
62.9%
|
| >=65 years |
2
66.7%
|
0
0%
|
2
66.7%
|
0
0%
|
9
45%
|
13
37.1%
|
| Age (years) [Median (Full Range) ] | ||||||
| Median (Full Range) [years] |
69
|
58
|
67
|
55
|
59
|
58
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
0
0%
|
1
33.3%
|
0
0%
|
1
16.7%
|
7
35%
|
9
25.7%
|
| Male |
3
100%
|
2
66.7%
|
3
100%
|
5
83.3%
|
13
65%
|
26
74.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
3
100%
|
3
100%
|
3
100%
|
6
100%
|
17
85%
|
32
91.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
15%
|
3
8.6%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
5%
|
2
5.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
10%
|
2
5.7%
|
| White |
3
100%
|
2
66.7%
|
3
100%
|
6
100%
|
15
75%
|
29
82.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
10%
|
2
5.7%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
3
100%
|
3
100%
|
3
100%
|
6
100%
|
20
100%
|
35
100%
|
Outcome Measures
| Title | Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability |
|---|---|
| Description | Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R |
| Time Frame | 1 year after last subjects received the first dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | Part 1: All Treated |
|---|---|---|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg PO + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 0,15, 20, and 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim |
| Measure Participants | 3 | 3 | 3 | 6 | 15 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
5%
|
| Title | Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR |
|---|---|
| Description | Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator. |
| Time Frame | 1 year after last subjects received the first dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Subjects Treated at RP2D | ABC Subjects Treated at RP2D |
|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim Note: There are only 17 samples available for DLBCL subtype test per GEP. Among of them 14 subjects were identified with ABC. |
| Measure Participants | 26 | 14 |
| Count of Participants [Participants] |
16
533.3%
|
9
300%
|
| Title | Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy |
|---|---|
| Description | Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator. |
| Time Frame | 1 year after last subjects received the first dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | Part 1: All Treated |
|---|---|---|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg PO + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 15 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 20 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 0,15, 20, and 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim |
| Measure Participants | 3 | 3 | 3 | 6 | 15 |
| Count of Participants [Participants] |
1
33.3%
|
2
66.7%
|
0
0%
|
3
50%
|
6
30%
|
| Title | Number of Subjects With Adverse Events as a Measure of Safety and Tolerability |
|---|---|
| Description | Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported. |
| Time Frame | 1 year after last subjects received the first dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Subjects Treated at RP2D | ABC Subjects Treated at RP2D |
|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim Note: There are only 17 samples available for DLBCL subtype test per GEP. Among of them 14 subjects were identified with ABC. |
| Measure Participants | 26 | 14 |
| Count of Participants [Participants] |
26
866.7%
|
14
466.7%
|
| Title | Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy |
|---|---|
| Description | Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause. OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology. |
| Time Frame | From initial dose date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose, up to 36 months at the most. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Subjects Treated at RP2D | ABC Subjects Treated at RP2D |
|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim Note: There are only 17 samples available for DLBCL subtype test per GEP. Among them 14 subjects were identified with ABC. |
| Measure Participants | 26 | 14 |
| Progression Free Survival (PFS) |
4.86
|
4.86
|
| Overall Survival (OS) |
15.84
|
15.84
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented. |
| Time Frame | From initial response date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | All Subjects Treated at RP2D Who Achieved Overall Response | ABC Subjects Treated at RP2D Who Achieved Overall Response |
|---|---|---|
| Arm/Group Description | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim Note: There are only 17 samples available for DLBCL subtype test per GEP. Among of them 14 subjects were identified with ABC. |
| Measure Participants | 16 | 9 |
| Median (Full Range) [Months] |
3.94
|
4.09
|
Adverse Events
| Time Frame | 3 years | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | All Subjects Treated at RP2D | |||||
| Arm/Group Description | Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 0 (PO) DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 15 (PO) DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 20 (PO) DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg PO + DA-EPOCH-R + lenalidomide 25 mg (PO) DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | Ibrutinib 560 mg (PO) +lenalidomide 25 mg (PO) + DA-EPOCH-R DA-EPOCH-R: Etoposide, Prednisone, Doxorubicin, Cyclophosphamide, Vincristine, Rituximab, Pegfilgrastim | |||||
All Cause Mortality |
||||||||||
| Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | All Subjects Treated at RP2D | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 5/6 (83.3%) | 3/26 (11.5%) | |||||
Serious Adverse Events |
||||||||||
| Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | All Subjects Treated at RP2D | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 5/6 (83.3%) | 19/26 (73.1%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Febrile neutropenia | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 6/26 (23.1%) | 6 |
| Anaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 2/26 (7.7%) | 2 |
| Thrombocytopenia | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Colitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Gastrointestinal haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Neutropenic colitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Vomiting | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| General disorders | ||||||||||
| Death | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Pyrexia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 3/26 (11.5%) | 3 |
| Infections and infestations | ||||||||||
| Abdominal wall abscess | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Clostridium difficile infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Enterococcal sepsis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Pneumonia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 3 |
| Pneumococcal sepsis | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Septic shock | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Fall | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hypokalaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 1/26 (3.8%) | 2 |
| Nervous system disorders | ||||||||||
| Syncope | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 2/26 (7.7%) | 2 |
| Renal and urinary disorders | ||||||||||
| Acute kidney injury | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hydronephrosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Urinary tract obstruction | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Diffuse alveolar damage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Vascular disorders | ||||||||||
| Hypotension | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 2/26 (7.7%) | 3 |
| Orthostatic hypotension | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Part 1: Dose Level 1 | Part 1: Dose Level 2 | Part 1: Dose Level 3 | Part 1: Dose Level 4 | All Subjects Treated at RP2D | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 6/6 (100%) | 26/26 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 3/3 (100%) | 11 | 3/3 (100%) | 29 | 2/3 (66.7%) | 22 | 4/6 (66.7%) | 16 | 12/26 (46.2%) | 42 |
| Thrombocytopenia | 3/3 (100%) | 12 | 1/3 (33.3%) | 4 | 1/3 (33.3%) | 7 | 3/6 (50%) | 6 | 12/26 (46.2%) | 28 |
| Leukopenia | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 4 | 1/3 (33.3%) | 5 | 2/6 (33.3%) | 5 | 4/26 (15.4%) | 11 |
| Neutropenia | 2/3 (66.7%) | 5 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 6 | 1/6 (16.7%) | 1 | 6/26 (23.1%) | 11 |
| Febrile neutropenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/6 (66.7%) | 4 | 5/26 (19.2%) | 5 |
| Lymphopenia | 0/3 (0%) | 0 | 2/3 (66.7%) | 13 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Increased tendency to bruise | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Leukocytosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Pancytopenia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Cardiac disorders | ||||||||||
| Sinus tachycardia | 0/3 (0%) | 0 | 3/3 (100%) | 9 | 1/3 (33.3%) | 3 | 3/6 (50%) | 3 | 6/26 (23.1%) | 6 |
| Palpitations | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Atrial fibrillation | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Tachycardia | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Angina pectoris | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Atrial flutter | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Mitral valve incompetence | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||||||
| Atrial septal defect | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||
| Ear discomfort | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Eye disorders | ||||||||||
| Vision blurred | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Nausea | 1/3 (33.3%) | 4 | 3/3 (100%) | 10 | 1/3 (33.3%) | 6 | 5/6 (83.3%) | 7 | 12/26 (46.2%) | 21 |
| Constipation | 1/3 (33.3%) | 3 | 3/3 (100%) | 11 | 2/3 (66.7%) | 4 | 3/6 (50%) | 5 | 11/26 (42.3%) | 17 |
| Diarrhoea | 0/3 (0%) | 0 | 2/3 (66.7%) | 3 | 2/3 (66.7%) | 8 | 5/6 (83.3%) | 9 | 15/26 (57.7%) | 24 |
| Abdominal pain | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 3 | 1/3 (33.3%) | 3 | 2/6 (33.3%) | 5 | 4/26 (15.4%) | 7 |
| Abdominal distension | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 2 | 1/6 (16.7%) | 2 | 2/26 (7.7%) | 3 |
| Gastrooesophageal reflux disease | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Dry mouth | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Dysphagia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 3 |
| Anal incontinence | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Aphthous ulcer | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Cheilitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Dyspepsia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 4 |
| Faeces discoloured | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Flatulence | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Gastric polyps | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Gastritis | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Ileus | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Odynophagia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Oesophagitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Stomatitis | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 3 |
| Vomiting | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 4/26 (15.4%) | 9 |
| General disorders | ||||||||||
| Fatigue | 2/3 (66.7%) | 3 | 3/3 (100%) | 17 | 1/3 (33.3%) | 5 | 5/6 (83.3%) | 6 | 13/26 (50%) | 16 |
| Oedema peripheral | 1/3 (33.3%) | 1 | 3/3 (100%) | 8 | 3/3 (100%) | 4 | 2/6 (33.3%) | 3 | 7/26 (26.9%) | 8 |
| Pyrexia | 0/3 (0%) | 0 | 2/3 (66.7%) | 4 | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 5/26 (19.2%) | 6 |
| Non-cardiac chest pain | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 3/26 (11.5%) | 4 |
| Pain | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Asthenia | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 3 |
| Catheter site pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Chills | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 3 |
| Gait disturbance | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Injection site haematoma | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Oedema | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Peripheral swelling | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Immune system disorders | ||||||||||
| Hypogammaglobulinaemia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Infections and infestations | ||||||||||
| Fungal skin infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Kidney infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Oral candidiasis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Sinusitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Upper respiratory tract infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Urinary tract infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 4 | 2/26 (7.7%) | 5 |
| Urosepsis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| Laceration | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Allergic transfusion reaction | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Excoriation | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Fall | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 4 |
| Incision site pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Procedural pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Skin abrasion | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Wound haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Investigations | ||||||||||
| Weight decreased | 1/3 (33.3%) | 3 | 2/3 (66.7%) | 8 | 1/3 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Electrocardiogram QT prolonged | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Platelet count decreased | 0/3 (0%) | 0 | 1/3 (33.3%) | 19 | 1/3 (33.3%) | 6 | 1/6 (16.7%) | 2 | 4/26 (15.4%) | 6 |
| Weight increased | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Blood creatinine increased | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Immunoglobulins decreased | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Lymphocyte count decreased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 3 | 1/26 (3.8%) | 3 |
| Neutrophil count decreased | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Urine output decreased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Hypokalaemia | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 7 | 2/3 (66.7%) | 7 | 2/6 (33.3%) | 20 | 11/26 (42.3%) | 42 |
| Decreased appetite | 1/3 (33.3%) | 3 | 2/3 (66.7%) | 3 | 1/3 (33.3%) | 3 | 2/6 (33.3%) | 3 | 5/26 (19.2%) | 6 |
| Dehydration | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 1/3 (33.3%) | 1 | 3/6 (50%) | 3 | 4/26 (15.4%) | 4 |
| Hypoalbuminaemia | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 1/3 (33.3%) | 8 | 1/6 (16.7%) | 2 | 3/26 (11.5%) | 6 |
| Hyperglycaemia | 1/3 (33.3%) | 7 | 1/3 (33.3%) | 15 | 1/3 (33.3%) | 13 | 1/6 (16.7%) | 1 | 4/26 (15.4%) | 16 |
| Hypomagnesaemia | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 3 | 5/26 (19.2%) | 9 |
| Hyponatraemia | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 6 | 1/6 (16.7%) | 2 | 5/26 (19.2%) | 6 |
| Fluid overload | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hyperuricaemia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 3/26 (11.5%) | 3 |
| Hypervolaemia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hyperchloraemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hypernatraemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hyperphosphataemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hypocalcaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 4 | 3/26 (11.5%) | 6 |
| Hypoglycaemia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Hypophosphataemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 4/26 (15.4%) | 5 |
| Magnesium deficiency | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Malnutrition | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Metabolic acidosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Vitamin D deficiency | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 1/3 (33.3%) | 6 | 1/3 (33.3%) | 3 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 6/26 (23.1%) | 6 |
| Muscular weakness | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Myalgia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 3/26 (11.5%) | 3 |
| Pain in extremity | 1/3 (33.3%) | 4 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 3/26 (11.5%) | 3 |
| Arthralgia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 4/26 (15.4%) | 4 |
| Groin pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Muscle twitching | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Musculoskeletal pain | 0/3 (0%) | 0 | 1/3 (33.3%) | 4 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Musculoskeletal stiffness | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Pain in jaw | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Nervous system disorders | ||||||||||
| Dizziness | 1/3 (33.3%) | 1 | 3/3 (100%) | 6 | 2/3 (66.7%) | 2 | 3/6 (50%) | 6 | 8/26 (30.8%) | 16 |
| Peripheral sensory neuropathy | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 6 | 1/3 (33.3%) | 2 | 2/6 (33.3%) | 2 | 6/26 (23.1%) | 7 |
| Headache | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 6/26 (23.1%) | 6 |
| Hypoaesthesia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 3/26 (11.5%) | 3 |
| Dysgeusia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 4/26 (15.4%) | 4 |
| Peripheral motor neuropathy | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Somnolence | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Tremor | 0/3 (0%) | 0 | 2/3 (66.7%) | 5 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Depressed level of consciousness | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Dysarthria | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Lethargy | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Peroneal nerve palsy | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Post herpetic neuralgia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Syncope | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Insomnia | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 5 | 2/3 (66.7%) | 4 | 1/6 (16.7%) | 2 | 5/26 (19.2%) | 6 |
| Anxiety | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 3 | 1/3 (33.3%) | 2 | 2/6 (33.3%) | 2 | 4/26 (15.4%) | 4 |
| Confusional state | 0/3 (0%) | 0 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Depression | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Delusion | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Haematuria | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Urinary incontinence | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Acute kidney injury | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Dysuria | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Pollakiuria | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Renal haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Renal impairment | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 4 | 1/26 (3.8%) | 4 |
| Urinary retention | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Urinary tract pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 0/3 (0%) | 0 | 3/3 (100%) | 5 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Oropharyngeal pain | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 4/26 (15.4%) | 5 |
| Cough | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 4 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 4 |
| Dysphonia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Dyspnoea exertional | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Productive cough | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hypoxia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Nasal congestion | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Pleural effusion | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Rhinorrhoea | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Tachypnoea | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Wheezing | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/26 (7.7%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Ecchymosis | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Rash erythematous | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Rash maculo-papular | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 5/26 (19.2%) | 5 |
| Dermatitis | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Dermatitis acneiform | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Dry skin | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Erythema | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Hyperhidrosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/26 (7.7%) | 2 |
| Ingrowing nail | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Rash | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/26 (3.8%) | 1 |
| Skin ulcer | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/26 (3.8%) | 1 |
| Vascular disorders | ||||||||||
| Hypotension | 0/3 (0%) | 0 | 3/3 (100%) | 3 | 1/3 (33.3%) | 2 | 3/6 (50%) | 4 | 6/26 (23.1%) | 7 |
| Hypertension | 1/3 (33.3%) | 5 | 2/3 (66.7%) | 12 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Deep vein thrombosis | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
| Jugular vein distension | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/26 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Director of Clinical Operations |
|---|---|
| Organization | Pharmacyclics, LLC |
| Phone | 408-774-0330 |
| Clinical_Directors@pcyc.com |
Responsible Party:
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
NCT02142049
Other Study ID Numbers:
- PCYC-1124-CA
First Posted:
May 20, 2014
Last Update Posted:
Feb 5, 2019
Last Verified:
May 1, 2018