Trial Outcomes & Findings for A Study of Galunisertib in Participants With Myelodysplastic Syndromes (NCT NCT02008318)
NCT ID: NCT02008318
Last Updated: 2019-09-11
Results Overview
Percentage of participants with hematological improvement (HI) based on International Working Group (IWG) 2006 criteria in participants with very low, low, and intermediate-risk myelodysplastic syndromes treated with Galunisertib plus best supportive care, as assessed by the International Prognostic Scoring System (IPSS-R). To be classified as an HI responder, the HI response must have lasted at least 8 weeks (56 days).
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
43 participants
Primary outcome timeframe
Baseline through end of study treatment (24 weeks)
Results posted on
2019-09-11
Participant Flow
This is a single-arm study (Galunisertib at 150 milligram \[mg\]); the Galunisertib at 80 mg was considered exploratory and only conducted in parallel with the main study, at one site in Spain.
Participant milestones
| Measure |
Galunisertib at 150 mg
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
Galunisertib at 80 mg
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
|---|---|---|
|
Overall Study
STARTED
|
41
|
2
|
|
Overall Study
Received At Least 1 Dose of Study Drug
|
41
|
2
|
|
Overall Study
COMPLETED
|
29
|
1
|
|
Overall Study
NOT COMPLETED
|
12
|
1
|
Reasons for withdrawal
| Measure |
Galunisertib at 150 mg
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
Galunisertib at 80 mg
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
0
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Progressive Disease
|
2
|
0
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
Baseline Characteristics
A Study of Galunisertib in Participants With Myelodysplastic Syndromes
Baseline characteristics by cohort
| Measure |
Galunisertib at 150 mg
n=41 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Galunisertib at 80 mg
n=2 Participants
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.49 years
STANDARD_DEVIATION 7.65 • n=99 Participants
|
62.50 years
STANDARD_DEVIATION 10.61 • n=107 Participants
|
70.12 years
STANDARD_DEVIATION 7.83 • n=206 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
32 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
41 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
43 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
Italy
|
8 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Region of Enrollment
Germany
|
23 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Region of Enrollment
Spain
|
10 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
IPSS-R Prognostic Risk Score
Very Low= (≤1.5)
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
IPSS-R Prognostic Risk Score
Low= (>1.5 - 3)
|
30 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
IPSS-R Prognostic Risk Score
Intermediate= (>3 - 4.5)
|
9 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline through end of study treatment (24 weeks)Population: Participants who received at least one dose of study drug.
Percentage of participants with hematological improvement (HI) based on International Working Group (IWG) 2006 criteria in participants with very low, low, and intermediate-risk myelodysplastic syndromes treated with Galunisertib plus best supportive care, as assessed by the International Prognostic Scoring System (IPSS-R). To be classified as an HI responder, the HI response must have lasted at least 8 weeks (56 days).
Outcome measures
| Measure |
Galunisertib at 150 mg
n=41 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Arm: Galunisertib at 80 mg
n=2 Participants
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles.
|
|---|---|---|
|
Percentage of Participants With Hematological Improvement (HI)
|
31.7 percentage of participants
Interval 18.1 to 48.1
|
0.0 percentage of participants
Interval 0.0 to 84.2
|
PRIMARY outcome
Timeframe: Baseline through end of study treatment (24 weeks)Population: Participants who received at least one dose of study drug during Phase 3.
Comparison of the percentage of participants with very low-, low-,and intermediate-risk MDS who were transfusion-free or had an increase ≥1.5 g/dL in hemoglobin (Hb) maintained for at least 8 weeks within the first 24 weeks of treatment with galunisertib plus best supportive care or placebo plus best supportive care and assessed by IPSS-R. The Phase 3 portion of this study was not conducted because efficacy level required in phase 2 to move forward to phase 3 was not achieved.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Follow up (final visit up to 24 months)Population: Participants who received at least one dose of study drug.
The Brief Fatigue Inventory (BFI) is a brief participant-reported questionnaire that measures the severity of fatigue based on the worst fatigue experienced during the past 24-hours. The severity of fatigue is assessed using an 11-point numeric scale, with 0 = no fatigue and 10 = fatigue as bad as you can imagine.
Outcome measures
| Measure |
Galunisertib at 150 mg
n=41 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Arm: Galunisertib at 80 mg
n=2 Participants
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles.
|
|---|---|---|
|
Change From Baseline in Brief Fatigue Inventory (BFI)
Current Fatigue at Follow-up
|
0.818 units on a scale
Standard Error 0.42
|
-1.005 units on a scale
Standard Error 2.08
|
|
Change From Baseline in Brief Fatigue Inventory (BFI)
Usual Fatigue at Follow-up
|
-0.017 units on a scale
Standard Error 0.37
|
-0.157 units on a scale
Standard Error 1.87
|
|
Change From Baseline in Brief Fatigue Inventory (BFI)
Worst Fatigue at Follow-up
|
-0.191 units on a scale
Standard Error 0.38
|
-0.063 units on a scale
Standard Error 1.93
|
SECONDARY outcome
Timeframe: Phase 3: Baseline, Cycle 2, Cycle 4, Cycle 6 (Cycle = 28 days)Population: Participants who received at least one dose of study drug during Phase 3.
EuroQol 5-Dimension 5 Level Instrument (EQ-5D-5L) was not conducted, trial terminated prior to Phase 3. No data collected.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline through end of study treatment (24 weeks)Population: Participants who received at least one dose of study drug.
Percentage of Participants with Cytogenetic Response with either complete or partial response. Complete cytogenetic response is the disappearance of the chromosomal abnormality without appearance of new ones. Partial cytogenetic response is at least 50% reduction of the chromosomal abnormality.
Outcome measures
| Measure |
Galunisertib at 150 mg
n=41 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Arm: Galunisertib at 80 mg
n=2 Participants
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles.
|
|---|---|---|
|
Percentage of Participants With Cytogenetic Response
|
2.4 percentage of participants
Interval 0.1 to 12.9
|
0 percentage of participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline through end of study treatment (24 weeks)Population: Participants who received at least one dose of study drug.
Percentage of any participant with a hospitalization admission and discharge date on the same day are counted as a half-day in the duration of hospitalization.
Outcome measures
| Measure |
Galunisertib at 150 mg
n=41 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Arm: Galunisertib at 80 mg
n=2 Participants
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles.
|
|---|---|---|
|
Percentage of Participants Who Are Hospitalized (Resource Utilization)
|
24.3 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 pre-dose & between 0.5 to 2 hours post dose; Day 14 pre-dose, between 0.5 to 2 & between 3 to 5 hours post dose; Days 15 & 16 (if logistically possible) between 0.5 to 2 hours post dosePopulation: All participants who received at least one dose of study drug, regardless of dose, with evaluable PK data.
Population mean (between-participant coefficient variation \[CV%\]) apparent clearance.
Outcome measures
| Measure |
Galunisertib at 150 mg
n=43 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Arm: Galunisertib at 80 mg
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles.
|
|---|---|---|
|
Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib
|
32 Liter per hour (L/h)
Geometric Coefficient of Variation 52
|
—
|
SECONDARY outcome
Timeframe: Baseline to date of death from any cause (Up to 2 years)Population: Participants who received at least one dose of study drug excluding the exploratory participants.
Overall survival is defined as the time from the date of first dose to the date of death from any cause.
Outcome measures
| Measure |
Galunisertib at 150 mg
n=41 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Arm: Galunisertib at 80 mg
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles.
|
|---|---|---|
|
Overall Survival (OS)
|
679 days
Interval 29.0 to 729.0
|
—
|
SECONDARY outcome
Timeframe: Baseline, Cycle 6 (Cycle = 28 days)Population: Participants who received at least one dose of study drug and had both a baseline and postbaseline assessment excluding the exploratory participants.
Change from baseline in bone marrow fibrosis measured the number of participants with a change in bone marrow fibrosis grading (negative, mild, moderate, and severe).
Outcome measures
| Measure |
Galunisertib at 150 mg
n=30 Participants
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines.
|
Arm: Galunisertib at 80 mg
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14... more days with no study drug (28 day cycles). Completed participants completed at least 6 cycles.
|
|---|---|---|
|
Number of Participants With a Change in Bone Marrow Fibrosis Grading
|
11 participants
|
—
|
Adverse Events
Galunisertib at 150 mg
Serious events: 8 serious events
Other events: 33 other events
Deaths: 0 deaths
Galunisertib at 80 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Galunisertib at 150 mg
n=41 participants at risk
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
Galunisertib at 80 mg
n=2 participants at risk
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.4%
1/41 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
2.4%
1/41 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Cardiac disorders
Cardiac failure
|
4.9%
2/41 • Number of events 2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Gastrointestinal disorders
Crohn's disease
|
2.4%
1/41 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
2.4%
1/41 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Infections and infestations
Pneumonia
|
2.4%
1/41 • Number of events 2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Infections and infestations
Respiratory syncytial virus infection
|
2.4%
1/41 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Infections and infestations
Tongue abscess
|
2.4%
1/41 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.9%
2/41 • Number of events 2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
Other adverse events
| Measure |
Galunisertib at 150 mg
n=41 participants at risk
Galunisertib at 150 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
Galunisertib at 80 mg
n=2 participants at risk
Exploratory arm: Galunisertib at 80 mg given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles).
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.3%
3/41 • Number of events 18 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Gastrointestinal disorders
Diarrhoea
|
17.1%
7/41 • Number of events 8 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Gastrointestinal disorders
Nausea
|
7.3%
3/41 • Number of events 4 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Gastrointestinal disorders
Vomiting
|
12.2%
5/41 • Number of events 6 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
General disorders
Asthenia
|
12.2%
5/41 • Number of events 13 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
50.0%
1/2 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
General disorders
Fatigue
|
9.8%
4/41 • Number of events 4 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
General disorders
Oedema peripheral
|
7.3%
3/41 • Number of events 3 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
General disorders
Pyrexia
|
12.2%
5/41 • Number of events 8 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Infections and infestations
Nasopharyngitis
|
9.8%
4/41 • Number of events 4 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.3%
3/41 • Number of events 3 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Nervous system disorders
Dizziness
|
7.3%
3/41 • Number of events 3 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
0.00%
0/2 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/41 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
50.0%
1/2 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/41 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
50.0%
1/2 • Number of events 1 • Baseline through end of study treatment or death from any cause (Up to 2 years)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60