Trial Outcomes & Findings for Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM) (NCT NCT01303965)
NCT ID: NCT01303965
Last Updated: 2019-01-08
Results Overview
The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
14 participants
Primary outcome timeframe
28 days
Results posted on
2019-01-08
Participant Flow
This protocol was a Phase I/II study. Phase I was based on a 3+3 design with the first cohort found to be safe with 3 patients. Phase II was based on a Simon Minimax two-stage design with the first interim analysis planned after 28 patients. The study was stopped at 11 patients in Phase II due to slow accrual.
Participant milestones
| Measure |
Phase I Dose Finding
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
Phase II
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
11
|
|
Overall Study
COMPLETED
|
0
|
1
|
|
Overall Study
NOT COMPLETED
|
3
|
10
|
Reasons for withdrawal
| Measure |
Phase I Dose Finding
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
Phase II
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Death
|
0
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Disease Progression
|
1
|
6
|
Baseline Characteristics
Allo Transplant Followed by Lenalidomide and Sirolimus Maintenance in High-Risk Multiple Myeloma (MM)
Baseline characteristics by cohort
| Measure |
Phase I Dose Finding
n=3 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
Phase II
n=11 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
57.1 years
STANDARD_DEVIATION 2.44 • n=93 Participants
|
52.8 years
STANDARD_DEVIATION 8.70 • n=4 Participants
|
53.7 years
STANDARD_DEVIATION 7.9 • n=27 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 28 daysPopulation: All patients assigned to Phase I and received treatment medication.
The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.
Outcome measures
| Measure |
Phase I Dose Finding
n=3 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase I: Number of Participants With Dose Limiting Toxicity
|
0 Participants
|
PRIMARY outcome
Timeframe: Transplant (Day 0) through 1 year post-transplantPopulation: All patients who received treatment and were followed after transplant.
Percent of patients and the 95% Binomial Confidence interval who were alive and free of progression at 12 months following transplant for the patients in Phase II. Progression will be based on International Myeloma Working Group criteria where patients may meet any one of the following criteria - increase of 25% or more in serum or urine M-protein from baseline, Serum M-protein and/or the absolute increase must be \>=0.5 g/dl, Urine M-protein and/or absolute increase must be \>=200 mg/24 hours, development of new bone lesions or soft tissue plasmacyomas or definite increase in the size of existing bone lesions or soft tissue plasmacyomas, or development of hypercalcemia (corrected serum Ca++\>11.5 mg/dl) that can be attributed solely to plasma cell proliferative disease.
Outcome measures
| Measure |
Phase I Dose Finding
n=11 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant
|
18.2 percentage of participants
Interval 2.3 to 51.8
|
SECONDARY outcome
Timeframe: Day 0 through 1 year post transplantationPopulation: All patients who received treatment and were followed after transplant
Percent of patients and the 95% Binomial Confidence interval who had any stage I-IV acute GvHD based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms for patients in Phase II. Zero means no acute GvHD was reported, and higher stages are worse outcomes (range of 0-4). For skin: 0=no rash; 1=erthematous macular rash over \<25% body surface; 2=over 25-50% of body surface; 4=bullae, exfoliation ulcerative dermatitis. For liver (bilirubin (mg/dL)): 0= \<2.0; 1= 2-\<2.9; 3= 3-\<5.9; 4= \>=15 . For gut changes (diarrhea\[ml/day\]): 0=none; 1= \>500-1000; 2= \>1000-1500; 3= \>1500; 4=severe abdominal pain with or without ileus. Overall grade 0: Skin=0; liver=0; gut changes=0. Overall grade 1: Skin with 1 or 2; liver=0; gut changes=0. Overall grade 2: Skin with 1, 2, or 3; liver=1; gut changes=1. Overall grade 3: Skin with 2 or 3; liver with 2 or 3; gut changes with 2 or 3. Overall grade 4: Patients with grade 4 toxicity in any organ system.
Outcome measures
| Measure |
Phase I Dose Finding
n=11 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)
|
36.4 percentage of participants
Interval 10.9 to 69.2
|
SECONDARY outcome
Timeframe: Transplant (Day 0) through 1 year post-transplantPopulation: All patients who received treatment and were followed after transplant
Percent of patients and the 95% Binomial Confidence interval who had any chronic GvHD reported based on Filipovich et al. consensus document (BB\&MT 2005) and Akpek et al. chronic GvHD grading system (Blood 2003) for patients in Phase II.
Outcome measures
| Measure |
Phase I Dose Finding
n=11 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD)
|
18.2 percentage of participants
Interval 2.3 to 51.8
|
SECONDARY outcome
Timeframe: 100 days post transplantPopulation: All patients who received treatment and were followed after transplant
Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 100 days for patients in Phase II.
Outcome measures
| Measure |
Phase I Dose Finding
n=11 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase II - Percent of Patients With Treatment-related Deaths at 100 Days
|
18.2 percentage of participants
Interval 2.3 to 51.8
|
SECONDARY outcome
Timeframe: Transplant (Day 0) through 1 year post-transplantPopulation: All patients who received treatment and were followed after transplant
Percent of patients and the 95% Binomial Confidence interval who had treatment-related deaths by 1 year for patients in Phase II.
Outcome measures
| Measure |
Phase I Dose Finding
n=11 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase II - Percent of Patients With Treatment-related Deaths at 1 Year
|
36.4 percentage of participants
Interval 10.9 to 69.2
|
SECONDARY outcome
Timeframe: Transplant (Day 0) through 1 year post transplantPopulation: All patients who received treatment and survived at least 14 days after transplant
Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.
Outcome measures
| Measure |
Phase I Dose Finding
n=10 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase II - Time to Neutrophil Engraftment
|
11 days
Interval 10.0 to 12.0
|
SECONDARY outcome
Timeframe: Transplant (Day 0) through 1 year post-transplantPopulation: All patients who received treatment and who achieved platelet recovery/engraftment of platelets
Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.
Outcome measures
| Measure |
Phase I Dose Finding
n=10 Participants
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|
|
Phase II - Time to Platelet Engraftment
|
19 days
Interval 14.0 to 20.0
|
Adverse Events
Phase I Dose Finding
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase II
Serious events: 8 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I Dose Finding
n=3 participants at risk
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
Phase II
n=11 participants at risk
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Cardiac disorders
Cardiac disorders - Other
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Cardiac disorders
Chest pain - cardiac
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Cardiac disorders
Heart failure
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Ear and labyrinth disorders
Hearing impaired
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Eye disorders
Blurred vision
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Eye disorders
Keratitis
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
General disorders
Chills
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
General disorders
Edema limbs
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
General disorders
Fever
|
66.7%
2/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
General disorders
Pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Infections and infestations - Other
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Infections and infestations
Lung infection
|
33.3%
1/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Investigations
Creatinine increased
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Nervous system disorders
Nervous system disorders - Other
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Confusion
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Delirium
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Delusions
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Renal and urinary disorders
Acute kidney injury
|
33.3%
1/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Other
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Renal and urinary disorders
Urinary tract pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
Other adverse events
| Measure |
Phase I Dose Finding
n=3 participants at risk
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
Phase II
n=11 participants at risk
Standard treatment of sirolimus and tacrolimus as GvHD prophylaxis with sirolimus (target plasma drug level of 5-10 ng/ml) and lenalidomide (15 mg daily) as post-transplant maintenance
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
33.3%
1/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Cardiac disorders
Sinus tachycardia
|
33.3%
1/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Eye disorders
Blurred vision
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Eye disorders
Dry eye
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
1/3 • up to 3 years
|
54.5%
6/11 • up to 3 years
|
|
Gastrointestinal disorders
Anal pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
66.7%
2/3 • up to 3 years
|
90.9%
10/11 • up to 3 years
|
|
Gastrointestinal disorders
Dry mouth
|
33.3%
1/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Lip pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
66.7%
2/3 • up to 3 years
|
45.5%
5/11 • up to 3 years
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3 • up to 3 years
|
90.9%
10/11 • up to 3 years
|
|
Gastrointestinal disorders
Oral pain
|
33.3%
1/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Gastrointestinal disorders
Rectal pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
2/3 • up to 3 years
|
63.6%
7/11 • up to 3 years
|
|
General disorders
Chills
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
General disorders
Edema face
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
General disorders
Edema limbs
|
66.7%
2/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
General disorders
Facial pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
General disorders
Fatigue
|
66.7%
2/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
General disorders
Fever
|
100.0%
3/3 • up to 3 years
|
72.7%
8/11 • up to 3 years
|
|
General disorders
Gait disturbance
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
General disorders
General disorders and administration site conditions - Other
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
General disorders
Localized edema
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
General disorders
Non-cardiac chest pain
|
33.3%
1/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
General disorders
Pain
|
66.7%
2/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Immune system disorders
Allergic reaction
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Infections and infestations
Abdominal infection
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Bronchial infection
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Infections and infestations
Eye infection
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Gum infection
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Infections and infestations - Other
|
66.7%
2/3 • up to 3 years
|
63.6%
7/11 • up to 3 years
|
|
Infections and infestations
Laryngitis
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Otitis media
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Sepsis
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Sinusitis
|
66.7%
2/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Infections and infestations
Skin infection
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Infections and infestations
Upper respiratory infection
|
33.3%
1/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Investigations
Alanine aminotransferase increased
|
100.0%
3/3 • up to 3 years
|
45.5%
5/11 • up to 3 years
|
|
Investigations
Alkaline phosphatase increased
|
66.7%
2/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
100.0%
3/3 • up to 3 years
|
72.7%
8/11 • up to 3 years
|
|
Investigations
Blood bilirubin increased
|
66.7%
2/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Investigations
Creatinine increased
|
100.0%
3/3 • up to 3 years
|
72.7%
8/11 • up to 3 years
|
|
Investigations
INR increased
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
1/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
1/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
33.3%
1/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
66.7%
2/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • up to 3 years
|
54.5%
6/11 • up to 3 years
|
|
Nervous system disorders
Nervous system disorders - Other
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Nervous system disorders
Sinus pain
|
33.3%
1/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Agitation
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Confusion
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Psychiatric disorders
Depression
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Hallucinations
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Renal and urinary disorders
Bladder spasm
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Other
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Renal and urinary disorders
Urinary tract pain
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
66.7%
2/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
66.7%
2/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
66.7%
2/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Scalp pain
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
33.3%
1/3 • up to 3 years
|
36.4%
4/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
0.00%
0/3 • up to 3 years
|
9.1%
1/11 • up to 3 years
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • up to 3 years
|
27.3%
3/11 • up to 3 years
|
|
Vascular disorders
Hypotension
|
33.3%
1/3 • up to 3 years
|
18.2%
2/11 • up to 3 years
|
|
Vascular disorders
Thromboembolic event
|
33.3%
1/3 • up to 3 years
|
0.00%
0/11 • up to 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place