Trial Outcomes & Findings for Phase I Study of Eltrombopag for Promoting Thrombopoiesis After Total Body Irradiation (NCT NCT00903929)
NCT ID: NCT00903929
Last Updated: 2016-05-05
Results Overview
The MTD was defined as the highest dose if no dose limiting toxicity was observed, or the highest dose at which less than one-third of the patients experienced toxicities not expected in the standard stem cell transplantation setting.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
19 participants
Primary outcome timeframe
1.5 years
Results posted on
2016-05-05
Participant Flow
Participant milestones
| Measure |
Eltrombopag 75 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
Eltrombopag 150 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
Eltrombopag 225 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
Eltrombopag 300 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
4
|
9
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
3
|
Reasons for withdrawal
| Measure |
Eltrombopag 75 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
Eltrombopag 150 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
Eltrombopag 225 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
Eltrombopag 300 mg
Dose escalation was based on a standard 3+3 design. A group of 3 patients were enrolled at a given dose level; if none of these patients experienced dose-limiting toxicity (DLT), then the dose could be escalated. If 1 of the 3 patients experienced DLT, then 3 more patients would be enrolled at the same dose level. If no additional patients experienced a DLT, then dose escalation could occur, but if 2 or more of the 6 patients experienced a DLT, then that dose would be the MTD.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
2
|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Phase I Study of Eltrombopag for Promoting Thrombopoiesis After Total Body Irradiation
Baseline characteristics by cohort
| Measure |
Eltrombopag
n=19 Participants
Eltrombopag: dose escalation
|
|---|---|
|
Age, Continuous
|
52 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 1.5 yearsThe MTD was defined as the highest dose if no dose limiting toxicity was observed, or the highest dose at which less than one-third of the patients experienced toxicities not expected in the standard stem cell transplantation setting.
Outcome measures
| Measure |
All Participants
n=19 Participants
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Eltrombopag
|
300 mg/day
|
SECONDARY outcome
Timeframe: 1.5 yearsDetermined for all participants who completed at least 75% of the planned doses. Platelet engraftment was as defined by the Center for International Blood and Marrow Transplant Research as the first of 3 consecutive days of a platelet count 20,000/mL without platelet trans-fusions for 7 days and/or the first day of a platelet count 100,000/mL without platelet transfusions for 7 days.
Outcome measures
| Measure |
All Participants
n=19 Participants
|
|---|---|
|
Median Time to Platelet Engraftment
|
16 days
Interval 0.0 to 86.0
|
SECONDARY outcome
Timeframe: baseline to day of engraftmentOutcome measures
| Measure |
All Participants
n=19 Participants
|
|---|---|
|
Median Number of Platelet Transfusions up to the Day of Engraftment
|
4 units of platelets
Interval 0.0 to 68.0
|
Adverse Events
Eltrombopag
Serious events: 8 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Eltrombopag
n=19 participants at risk
Eltrombopag: dose escalation
|
|---|---|
|
Infections and infestations
urosepsis
|
5.3%
1/19
|
|
Vascular disorders
pumonary embolism
|
5.3%
1/19
|
|
Infections and infestations
cytomegalovirus infection with fever
|
5.3%
1/19
|
|
Infections and infestations
clostridium difficile infection
|
5.3%
1/19
|
|
Renal and urinary disorders
acute renal failure
|
15.8%
3/19
|
|
Gastrointestinal disorders
graft-versus-host disease of the gut
|
5.3%
1/19
|
|
Gastrointestinal disorders
gastroparesis
|
5.3%
1/19
|
|
Respiratory, thoracic and mediastinal disorders
acute respiratory distress syndrome
|
5.3%
1/19
|
|
Cardiac disorders
pericarditis
|
5.3%
1/19
|
|
Skin and subcutaneous tissue disorders
graft-versus-host disease skin rash
|
5.3%
1/19
|
Other adverse events
| Measure |
Eltrombopag
n=19 participants at risk
Eltrombopag: dose escalation
|
|---|---|
|
Cardiac disorders
hypertension
|
10.5%
2/19
|
|
General disorders
fatigue
|
10.5%
2/19
|
|
Gastrointestinal disorders
dehydration
|
10.5%
2/19
|
|
Gastrointestinal disorders
diarrhea
|
15.8%
3/19
|
|
Gastrointestinal disorders
dysphagia
|
15.8%
3/19
|
|
Gastrointestinal disorders
mucositis
|
26.3%
5/19
|
|
Gastrointestinal disorders
nausea
|
31.6%
6/19
|
|
Infections and infestations
fever
|
31.6%
6/19
|
|
Infections and infestations
infection with normal absolute neutrophil count
|
10.5%
2/19
|
|
Infections and infestations
BK viruria
|
10.5%
2/19
|
|
Infections and infestations
CMV reactivation
|
21.1%
4/19
|
|
Blood and lymphatic system disorders
edema
|
15.8%
3/19
|
|
Endocrine disorders
hyperglycemia
|
47.4%
9/19
|
|
Endocrine disorders
hypertriglyceridemia
|
10.5%
2/19
|
|
Endocrine disorders
hypocalcemia
|
10.5%
2/19
|
|
Endocrine disorders
hypomagnesemia
|
10.5%
2/19
|
|
Endocrine disorders
hypokalemia
|
26.3%
5/19
|
|
Endocrine disorders
hypophosphatemia
|
15.8%
3/19
|
|
Nervous system disorders
syncope
|
10.5%
2/19
|
|
Gastrointestinal disorders
pain
|
15.8%
3/19
|
|
Nervous system disorders
headache
|
21.1%
4/19
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
15.8%
3/19
|
|
Respiratory, thoracic and mediastinal disorders
hiccoughs
|
10.5%
2/19
|
|
Renal and urinary disorders
renal failure
|
15.8%
3/19
|
|
Hepatobiliary disorders
alanine aminotransferase elevation
|
89.5%
17/19
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place