Trial Outcomes & Findings for EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma (NCT NCT00114738)
NCT ID: NCT00114738
Last Updated: 2022-10-10
Results Overview
Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
53 participants
Primary outcome timeframe
up to 5 years
Results posted on
2022-10-10
Participant Flow
Participant milestones
| Measure |
Bortezomib Then Bortezomib + DA-EPOCH-R Induction
Bortezomib is given alone for one cycle, then combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B) is given every 3 weeks for 6 cycles.
|
Bortezomib Maintenance
Bortezomib alone is given in 3 week cycles. 3-week cycles continue up to 18 months or until the disease comes back or worsens.
|
Observation
Participants are observed without treatment.
|
|---|---|---|---|
|
Bortezomib Then Bortezomib + Induction
STARTED
|
53
|
0
|
0
|
|
Bortezomib Then Bortezomib + Induction
Started With Bortezomib Alone
|
47
|
0
|
0
|
|
Bortezomib Then Bortezomib + Induction
Skipped Bortezomib Alone
|
6
|
0
|
0
|
|
Bortezomib Then Bortezomib + Induction
COMPLETED
|
51
|
0
|
0
|
|
Bortezomib Then Bortezomib + Induction
NOT COMPLETED
|
2
|
0
|
0
|
|
Screening for Randomization
STARTED
|
51
|
0
|
0
|
|
Screening for Randomization
COMPLETED
|
30
|
0
|
0
|
|
Screening for Randomization
NOT COMPLETED
|
21
|
0
|
0
|
|
Randomization
STARTED
|
0
|
14
|
16
|
|
Randomization
COMPLETED
|
0
|
14
|
16
|
|
Randomization
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Bortezomib Then Bortezomib + DA-EPOCH-R Induction
Bortezomib is given alone for one cycle, then combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B) is given every 3 weeks for 6 cycles.
|
Bortezomib Maintenance
Bortezomib alone is given in 3 week cycles. 3-week cycles continue up to 18 months or until the disease comes back or worsens.
|
Observation
Participants are observed without treatment.
|
|---|---|---|---|
|
Bortezomib Then Bortezomib + Induction
Withdrawal by Subject
|
1
|
0
|
0
|
|
Bortezomib Then Bortezomib + Induction
Progressive Disease
|
1
|
0
|
0
|
|
Screening for Randomization
Neuropathy
|
17
|
0
|
0
|
|
Screening for Randomization
Progressive disease
|
2
|
0
|
0
|
|
Screening for Randomization
CNS Hemorrhage
|
1
|
0
|
0
|
|
Screening for Randomization
Other
|
1
|
0
|
0
|
Baseline Characteristics
EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma
Baseline characteristics by cohort
| Measure |
All Participants
n=53 Participants
All Participants who received at least one dose of Bortezomib alone followed by EPOCH-R+B chemotherapy.
Bortezomib (B): Bortezomib is given alone for one cycle.
Combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B)
Rituximab (R): Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.
EPOCH: EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.
Bortezomib (B): Bortezomib is given alone for one cycle. Bortezomib or observation: At the beginning of Part C, patients are randomized to receive bortezomib maintenance or be observed w/o bortezomib.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
39 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
14 Participants
n=5 Participants
|
|
Age, Continuous
|
58.85 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
49 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
53 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 5 yearsTime interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Outcome measures
| Measure |
Bortezomib Maintenance
n=14 Participants
Bortezomib maintenance
Bortezomib: Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.
|
Observation
n=16 Participants
Observation without bortezomib
|
Not Randomized
n=23 Participants
Twenty-three patients were not randomized. Sixteen due to neuropathy and seven due to "other" reasons.
|
|---|---|---|---|
|
Progression Free Survival (PFS)
|
27.2 Months
Interval 12.4 to 51.5
|
33.5 Months
Interval 20.3 to
That is a statistical reason; since the OS was so high, the upper limit of confidence interval is undefined.
|
7.8 Months
Interval 4.3 to 29.0
|
PRIMARY outcome
Timeframe: up to 9.9 yearsOverall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Outcome measures
| Measure |
Bortezomib Maintenance
n=53 Participants
Bortezomib maintenance
Bortezomib: Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.
|
Observation
Observation without bortezomib
|
Not Randomized
Twenty-three patients were not randomized. Sixteen due to neuropathy and seven due to "other" reasons.
|
|---|---|---|---|
|
Median Overall Survival (OS)
|
80.4 Months
Interval 66.6 to 89.0
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 9.9 yearsTime interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.
Outcome measures
| Measure |
Bortezomib Maintenance
n=53 Participants
Bortezomib maintenance
Bortezomib: Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.
|
Observation
Observation without bortezomib
|
Not Randomized
Twenty-three patients were not randomized. Sixteen due to neuropathy and seven due to "other" reasons.
|
|---|---|---|---|
|
Overall Progression Free Survival
|
29.3 Months
Interval 20.3 to 35.8
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 9.9 yearsOverall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.
Outcome measures
| Measure |
Bortezomib Maintenance
n=14 Participants
Bortezomib maintenance
Bortezomib: Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.
|
Observation
n=16 Participants
Observation without bortezomib
|
Not Randomized
n=23 Participants
Twenty-three patients were not randomized. Sixteen due to neuropathy and seven due to "other" reasons.
|
|---|---|---|---|
|
Overall Survival
|
78.6 Months
Interval 47.2 to 92.5
|
87.5 Months
Interval 58.6 to 96.7
|
31.6 Months
Interval 4.9 to
That is a statistical reason; since the OS was so high, the upper limit of confidence interval is undefined.
|
SECONDARY outcome
Timeframe: Date treatment consent signed to date off study, approximately 143 months and 7 daysPopulation: Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Outcome measures
| Measure |
Bortezomib Maintenance
n=53 Participants
Bortezomib maintenance
Bortezomib: Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.
|
Observation
Observation without bortezomib
|
Not Randomized
Twenty-three patients were not randomized. Sixteen due to neuropathy and seven due to "other" reasons.
|
|---|---|---|---|
|
Count of Participants With Serious and Non-Serious Adverse Events
|
53 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 22 weeks after initiation of therapyPopulation: Participants are grouped together in one arm/group because this is the arm/group in which all participants received drug.
Clinical response is assessed by the response criteria for lymphomas and is defined as a fraction of patients who have a complete response (CR) or a complete response (CR) + partial response (PR). A complete response is disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g. lactate dehydrogenase) definitely assignable to the lymphoma. Partial response is ≥50% decreased in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Progressive disease is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen, ≥50% increase in the absolute number of circulating lymphocytes.
Outcome measures
| Measure |
Bortezomib Maintenance
n=53 Participants
Bortezomib maintenance
Bortezomib: Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.
|
Observation
Observation without bortezomib
|
Not Randomized
Twenty-three patients were not randomized. Sixteen due to neuropathy and seven due to "other" reasons.
|
|---|---|---|---|
|
Clinical Response
Stable Disease
|
3.8 Percentage of patients
|
—
|
—
|
|
Clinical Response
Not Evaluable
|
1.9 Percentage of patients
|
—
|
—
|
|
Clinical Response
Overall Response (CR+PR)
|
92.5 Percentage of patients
|
—
|
—
|
|
Clinical Response
Complete Response
|
86.7 Percentage of patients
|
—
|
—
|
|
Clinical Response
Progressive Disease
|
1.9 Percentage of patients
|
—
|
—
|
Adverse Events
EPOCH-R+Bortezomib
Serious events: 21 serious events
Other events: 53 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
EPOCH-R+Bortezomib
n=53 participants at risk
Combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B)
Rituximab (R): Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.
EPOCH: EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.
Bortezomib (B): Bortezomib is given alone for one cycle.
|
|---|---|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Constipation
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Creatinine
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Death not associated with CTCAE term::Disease progression NOS
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Diarrhea
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Dizziness
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Esophagitis
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Febrile neutropenia
|
17.0%
9/53 • Number of events 11 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Hemorrhage, CNS
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Hemorrhage, GI::Peritoneal cavity
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with unknown ANC::Lung (pneumonia)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Obstruction, GI::Colon
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Obstruction, GI::Small bowel NOS
|
1.9%
1/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Pain::Abdomen NOS
|
1.9%
1/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Bone
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Perforation, GI::Colon
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Platelets
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
Other adverse events
| Measure |
EPOCH-R+Bortezomib
n=53 participants at risk
Combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B)
Rituximab (R): Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.
EPOCH: EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.
Bortezomib (B): Bortezomib is given alone for one cycle.
|
|---|---|
|
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)
|
35.8%
19/53 • Number of events 39 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Investigations
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
30.2%
16/53 • Number of events 28 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
67.9%
36/53 • Number of events 92 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
30.2%
16/53 • Number of events 22 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
3.8%
2/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)
|
22.6%
12/53 • Number of events 18 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Anorexia
|
32.1%
17/53 • Number of events 21 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Ascites (non-malignant)
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Ataxia (incoordination)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Bicarbonate, serum-low
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
24.5%
13/53 • Number of events 23 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
CPK (creatine phosphokinase)
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)
|
7.5%
4/53 • Number of events 9 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
37.7%
20/53 • Number of events 69 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Cardiac General - Other (cardiac tamponade)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Cardiac ischemia/infarction
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Cognitive disturbance
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Confusion
|
3.8%
2/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Constipation
|
60.4%
32/53 • Number of events 50 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Constitutional Symptoms - Other (early satiety
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.9%
10/53 • Number of events 12 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Creatinine
|
17.0%
9/53 • Number of events 15 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Renal and urinary disorders
Cystitis
|
1.9%
1/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Dehydration
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (folliculitis)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Diarrhea
|
56.6%
30/53 • Number of events 49 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Distension/bloating, abdominal
|
11.3%
6/53 • Number of events 7 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Dizziness
|
39.6%
21/53 • Number of events 26 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Dry eye syndrome
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Dry mouth/salivary gland (xerostomia)
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.3%
6/53 • Number of events 6 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Dysphagia (difficulty swallowing)
|
9.4%
5/53 • Number of events 5 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
30.2%
16/53 • Number of events 22 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Edema: head and neck
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Edema: limb
|
50.9%
27/53 • Number of events 41 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Esophagitis
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
FEV(1)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
66.0%
35/53 • Number of events 54 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Febrile neutropenia (fever of unknown origin
|
24.5%
13/53 • Number of events 15 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
26.4%
14/53 • Number of events 14 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Flatulence
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Flu-like syndrome
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Gastrointestinal - Other (hiccups)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
34.0%
18/53 • Number of events 48 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
11.3%
6/53 • Number of events 7 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
75.5%
40/53 • Number of events 48 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
17.0%
9/53 • Number of events 9 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
100.0%
53/53 • Number of events 392 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Hemorrhage, GI::Anus
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Hemorrhage, GI::Colon
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Hemorrhage, GI::Rectum
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory::Nose
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Hemorrhage/Bleeding - Other vitreous hemorrhage)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Hemorrhoids
|
1.9%
1/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccoughs (hiccups, singultus)
|
3.8%
2/53 • Number of events 9 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Hypertension
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Hypotension
|
28.3%
15/53 • Number of events 21 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.9%
1/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection - Other (sinusitis)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Abdomen NOS
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Bladder (urinary)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Eye NOS
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Lung (pneumonia)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Mucosa
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Nerve-peripheral
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Oral cavity-gums (gingivitis)
|
5.7%
3/53 • Number of events 5 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Sinus
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Skin (cellulitis)
|
7.5%
4/53 • Number of events 6 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOS
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Infections and infestations
Infection with unknown ANC::Soft tissue NOS
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Injection site reaction/extravasation changes
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Insomnia
|
34.0%
18/53 • Number of events 21 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Surgical and medical procedures
Intra-operative injury::Muscle
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Laryngeal nerve dysfunction
|
5.7%
3/53 • Number of events 5 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
100.0%
53/53 • Number of events 345 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
100.0%
53/53 • Number of events 451 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)
|
22.6%
12/53 • Number of events 22 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
24.5%
13/53 • Number of events 58 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Memory impairment
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Mood alteration::Agitation
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Mood alteration::Anxiety
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Mood alteration::Depression
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam)::Oral cavity
|
43.4%
23/53 • Number of events 46 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam)::Stomach
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (functional/symptomatic)::Oral cavity
|
20.8%
11/53 • Number of events 12 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)::Extremity-lower
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)::Whole body/generalized
|
7.5%
4/53 • Number of events 5 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
13.2%
7/53 • Number of events 7 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Nausea
|
50.9%
27/53 • Number of events 58 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Neurology - Other (autonomic neuropathy)
|
5.7%
3/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Neuropathy: motor
|
15.1%
8/53 • Number of events 9 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Neuropathy: sensory
|
98.1%
52/53 • Number of events 93 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
100.0%
53/53 • Number of events 271 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Obstruction, GI::Ileum
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Ophthalmoplegia/diplopia (double vision)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
PTT (Partial Thromboplastin Time)
|
30.2%
16/53 • Number of events 27 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Pain - Other (Specify, Jaw-GCSF)
|
15.1%
8/53 • Number of events 11 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Pain::Abdomen NOS
|
22.6%
12/53 • Number of events 14 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Back
|
20.8%
11/53 • Number of events 11 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Bone
|
60.4%
32/53 • Number of events 61 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Pain::Cardiac/heart
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Chest wall
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Chest/thorax NOS
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Extremity-limb
|
13.2%
7/53 • Number of events 9 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Pain::Head/headache
|
28.3%
15/53 • Number of events 20 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Joint
|
18.9%
10/53 • Number of events 10 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Renal and urinary disorders
Pain::Kidney
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Pain::Lymph node
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain::Muscle
|
17.0%
9/53 • Number of events 12 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Pain::Neuralgia/peripheral nerve
|
22.6%
12/53 • Number of events 18 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Pain::Oral cavity
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Pain::Pericardium
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Pain::Rectum
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pain::Throat/pharynx/larynx
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Renal and urinary disorders
Pain::Urethra
|
1.9%
1/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Palpitations
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Vascular disorders
Phlebitis (including superficial thrombosis)
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
24.5%
13/53 • Number of events 25 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Blood and lymphatic system disorders
Platelets
|
100.0%
53/53 • Number of events 419 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Potassium, serum-high (hyperkalemia)
|
11.3%
6/53 • Number of events 9 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
24.5%
13/53 • Number of events 24 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Proctitis
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Prolapse of stoma, GI
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Proteinuria
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
3.8%
2/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other (tachypnea)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
30.2%
16/53 • Number of events 18 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Rigors/chills
|
17.0%
9/53 • Number of events 11 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Seroma
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Skin breakdown/decubitus ulcer
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Sodium, serum-high (hypernatremia)
|
13.2%
7/53 • Number of events 8 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
37.7%
20/53 • Number of events 44 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia::Sinus bradycardia
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia::Sinus tachycardia
|
7.5%
4/53 • Number of events 6 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia::Supraventricular arrhythmia NOS
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Sweating (diaphoresis)
|
9.4%
5/53 • Number of events 6 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Syncope (fainting)
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
24.5%
13/53 • Number of events 17 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Vascular disorders
Thrombosis/embolism (vascular access-related)
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
11.3%
6/53 • Number of events 8 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Ear and labyrinth disorders
Tinnitus
|
3.8%
2/53 • Number of events 2 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)
|
13.2%
7/53 • Number of events 10 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
5.7%
3/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Renal and urinary disorders
Urinary retention (including neurogenic bladder)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Renal and urinary disorders
Urine color change
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Urticaria (hives, welts, wheals)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Cardiac disorders
Ventricular arrhythmia::Ventricular tachycardia
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Vascular disorders
Vessel injury-vein::Extremity-upper
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Vision-blurred vision
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Vision-flashing lights/floaters
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Vision-photophobia
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)
|
7.5%
4/53 • Number of events 4 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Vomiting
|
22.6%
12/53 • Number of events 15 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Eye disorders
Watery eye (epiphora, tearing)
|
20.8%
11/53 • Number of events 14 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Weight gain
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Weight loss
|
15.1%
8/53 • Number of events 13 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Gastrointestinal - Other (Stomatitis)
|
3.8%
2/53 • Number of events 3 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Gastrointestinal - Other (Stomatitis - Ulcer on tongue)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Gastrointestinal - Other (Thrush)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Gastrointestinal disorders
Gastrointestinal - Other (Stomatitis/pharyngitis)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Neurology - Other (fall)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Nervous system disorders
Pain - Other (neuropathic)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
General disorders
Pain - Other (pain Lt biopsy site)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain - Other (pain R arm)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain - Other (pain in extremity)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Skin and subcutaneous tissue disorders
Pain - Other (skin/shingles)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pain - Other (sore throat)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Surgical and medical procedures
Pain - Other (surgical site)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain - Other (arm)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
|
Musculoskeletal and connective tissue disorders
Pain - Other (extremities)
|
1.9%
1/53 • Number of events 1 • date treatment consent signed to date off study, approximately 143 months and 7 days
Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place