Trial Outcomes & Findings for LAM Pilot Study With Imatinib Mesylate (NCT NCT03131999)
NCT ID: NCT03131999
Last Updated: 2020-06-16
Results Overview
Change in the square root of the intrasubject plasma VEGF-D
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
18 participants
Primary outcome timeframe
Before and 1 month after initiation of monotherapy imatinib mesylate or placebo
Results posted on
2020-06-16
Participant Flow
18 Subjects signed consent, 2 subjects failed baseline evaluation and were not randomized. 1 subject was randomized, took 4 placebo pills and stopped (without side effects) and is deemed not evaluable.
Participant milestones
| Measure |
Imatinib Mesylate 400mg Capsule
56 days of Imatinib mesylate 400 mg oral daily with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction to 200 mg daily is allowed for toxicity.
Imatinib Mesylate 400Mg Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
Placebo Capsule
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Placebo - Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Imatinib Mesylate 400mg Capsule
56 days of Imatinib mesylate 400 mg oral daily with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction to 200 mg daily is allowed for toxicity.
Imatinib Mesylate 400Mg Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
Placebo Capsule
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Placebo - Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
LAM Pilot Study With Imatinib Mesylate
Baseline characteristics by cohort
| Measure |
Imatinib Mesylate 400mg Capsule
n=8 Participants
56 days of Imatinib mesylate 400 mg oral daily with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction to 200 mg daily is allowed for toxicity.
Imatinib Mesylate 400Mg Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
Placebo Capsule
n=7 Participants
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Placebo - Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45 years
STANDARD_DEVIATION 12 • n=39 Participants
|
50 years
STANDARD_DEVIATION 11 • n=41 Participants
|
47.7 years
STANDARD_DEVIATION 12 • n=35 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=39 Participants
|
7 Participants
n=41 Participants
|
15 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Forced Expiratory Volume in 1 Second
|
59 Percent predicted
STANDARD_DEVIATION 23.1 • n=39 Participants
|
60 Percent predicted
STANDARD_DEVIATION 15.4 • n=41 Participants
|
59.5 Percent predicted
STANDARD_DEVIATION 18.8 • n=35 Participants
|
PRIMARY outcome
Timeframe: Before and 1 month after initiation of monotherapy imatinib mesylate or placeboChange in the square root of the intrasubject plasma VEGF-D
Outcome measures
| Measure |
Imatinib Mesylate 400mg Capsule
n=8 Participants
56 days of Imatinib mesylate 400 mg oral daily with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction to 200 mg daily is allowed for toxicity.
Imatinib Mesylate 400Mg Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
Placebo Capsule
n=7 Participants
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Placebo - Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
|---|---|---|
|
Serum VEGF-D
|
0.05 Log transformed VEGF-D change pg/dL
Standard Deviation 0.10
|
0.07 Log transformed VEGF-D change pg/dL
Standard Deviation 0.13
|
SECONDARY outcome
Timeframe: 3 monthsAdverse event and Serious Adverse Event numbers using the CTCAE Version 4.03 definitions
Outcome measures
| Measure |
Imatinib Mesylate 400mg Capsule
n=8 Participants
56 days of Imatinib mesylate 400 mg oral daily with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction to 200 mg daily is allowed for toxicity.
Imatinib Mesylate 400Mg Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
Placebo Capsule
n=7 Participants
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Placebo - Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
|---|---|---|
|
Adverse Events
Adverse Events
|
10 number of events
|
12 number of events
|
|
Adverse Events
Serious Adverse Events
|
0 number of events
|
0 number of events
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 monthsFEV1 % predicted change
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 monthsSaint Georges Respiratory Questionnaire change
Outcome measures
Outcome data not reported
Adverse Events
Imatinib Mesylate 400mg Capsule
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo Capsule
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Imatinib Mesylate 400mg Capsule
n=8 participants at risk
56 days of Imatinib mesylate 400 mg oral daily with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction to 200 mg daily is allowed for toxicity.
Imatinib Mesylate 400Mg Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
Placebo Capsule
n=7 participants at risk
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Placebo - Capsule: Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
|
|---|---|---|
|
Gastrointestinal disorders
Nausea and/or vomitting
|
50.0%
4/8 • Number of events 4 • 3 months
|
57.1%
4/7 • Number of events 4 • 3 months
|
|
General disorders
Fatigue
|
37.5%
3/8 • Number of events 3 • 3 months
|
0.00%
0/7 • 3 months
|
|
General disorders
Insomnia
|
0.00%
0/8 • 3 months
|
28.6%
2/7 • Number of events 2 • 3 months
|
|
Nervous system disorders
Headache
|
0.00%
0/8 • 3 months
|
42.9%
3/7 • Number of events 3 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Elevated Trough Sirolimus
|
25.0%
2/8 • Number of events 2 • 3 months
|
14.3%
1/7 • Number of events 1 • 3 months
|
|
Gastrointestinal disorders
Diarrhea
|
12.5%
1/8 • Number of events 1 • 3 months
|
28.6%
2/7 • Number of events 2 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxemia
|
12.5%
1/8 • Number of events 1 • 3 months
|
0.00%
0/7 • 3 months
|
Additional Information
Charlton Strange, MD
Medical University of South Carolina
Phone: 843-792-3174
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place