Trial Outcomes & Findings for Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis (NCT NCT01687179)
NCT ID: NCT01687179
Last Updated: 2018-10-11
Results Overview
The Primary endpoint of this study was safety. Safety was assessed based on the adverse events and serious adverse events that occurred in these patients when they were on this combination therapy. Percentage of adverse events in each system at a dose was calculated from the total adverse events at that dose. Subjects were closely monitored and adverse events were classified and graded according to the "Common Terminology Criteria for Adverse Events, (CTCAE) Version 4.0".
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
14 participants
Primary outcome timeframe
48 weeks
Results posted on
2018-10-11
Participant Flow
Participant milestones
| Measure |
Sirolimus and Hydroxychloroquine 200 mg
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily.
|
Sirolimus and HydroxyChloroquine 400 mg
Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day.
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
10
|
|
Overall Study
COMPLETED
|
2
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
1 subject screen failed.
Baseline characteristics by cohort
| Measure |
Sirolimus and Hydroxychloroquine
n=14 Participants
Subjects will take sirolimus at an initial dose of 2mg followed by dose adjustment to keep sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to sirolimus subjects will receive hydroxychloroquine at 200 mg daily or twice a day for 6 months, depending on time of enrollment into the study, following a standard phase I dose escalation.
sirolimus and hydroxychloroquine: This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily.
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|---|---|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=13 Participants • 1 subject screen failed.
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=13 Participants • 1 subject screen failed.
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Age, Continuous
|
49 years
n=13 Participants • 1 subject screen failed.
|
|
Sex: Female, Male
Female
|
13 Participants
n=13 Participants • 1 subject screen failed.
|
|
Sex: Female, Male
Male
|
0 Participants
n=13 Participants • 1 subject screen failed.
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=13 Participants • 1 subject screen failed.
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=13 Participants • 1 subject screen failed.
|
|
Race (NIH/OMB)
White
|
12 Participants
n=13 Participants • 1 subject screen failed.
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=13 Participants • 1 subject screen failed.
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=13 Participants • 1 subject screen failed.
|
|
Region of Enrollment
United States
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13 Participants
n=13 Participants • 1 subject screen failed.
|
|
Post-Menopause
|
6 Participants
n=13 Participants • 1 subject screen failed.
|
|
Pneumothorax
|
9 Participants
n=13 Participants • 1 subject screen failed.
|
|
Angiomyolipoma
|
2 Participants
n=13 Participants • 1 subject screen failed.
|
|
Tuberous Sclerois (TSC)- Lymphangioleiomyomatosis (LAM)
|
0 Participants
n=14 Participants
|
|
Lung Biopsy
|
8 Participants
n=13 Participants • 1 subject screen failed.
|
|
Chylothorax
|
1 Participants
n=13 Participants • 1 subject screen failed
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|
6 minute walk distance (6MWD) (m)
|
442 m
STANDARD_DEVIATION 103 • n=13 Participants • 1 subject screen failed.
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|
St. George's Respiratory Questionnaire (SGRQ)
|
43.8 units on a scale
STANDARD_DEVIATION 19.2 • n=13 Participants • 1 subject screen failed.
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|
Log VEGF-D (Veascular Endothelial Growth factor)
|
3.11 log(pg/ml)
STANDARD_DEVIATION 0.33 • n=13 Participants • 1 subject screen failed.
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FEV1
|
1.6 Litres
STANDARD_DEVIATION 0.7 • n=13 Participants • 1 Subject Screen failed.
|
|
FEV1 (%)
|
59 Percent predicted
STANDARD_DEVIATION 21 • n=14 Participants
|
|
FVC (L)
|
2.8 Litres
STANDARD_DEVIATION 0.7 • n=13 Participants • 1 subject screen failed.
|
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FVC (%)
|
81 Percent predicted
STANDARD_DEVIATION 16 • n=13 Participants • 1 Subject Screen failed.
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DLCO (ml/min/mmhg)
|
9.8 ml/min/mmhg
STANDARD_DEVIATION 3.1 • n=13 Participants • 1 Subject screen failed.
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DLCO (%)
|
43 percent predicted
STANDARD_DEVIATION 15 • n=13 Participants • 1 Subject screen failed.
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PRIMARY outcome
Timeframe: 48 weeksThe Primary endpoint of this study was safety. Safety was assessed based on the adverse events and serious adverse events that occurred in these patients when they were on this combination therapy. Percentage of adverse events in each system at a dose was calculated from the total adverse events at that dose. Subjects were closely monitored and adverse events were classified and graded according to the "Common Terminology Criteria for Adverse Events, (CTCAE) Version 4.0".
Outcome measures
| Measure |
Sirolimus and Hydroxychloroquine 200 mg
n=3 Participants
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily. Safety of the drug combination was assessed by the occurrence of adverse events in these 3 patients.
|
Sirolimus and Hydroxychloroquine 400 mg
n=10 Participants
Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day. Safety of this dose was assessed by the occurrence of adverse events in these 10 patients.
|
|---|---|---|
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Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Cardiac Disorders
|
2.27 Percentage of adverse events
|
1.11 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Eye Disorders
|
0 Percentage of adverse events
|
1.11 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
GI Disorders
|
18.18 Percentage of adverse events
|
22.22 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
General Disorders, Administration site condistions
|
18.18 Percentage of adverse events
|
6.67 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Immune System disorders
|
0 Percentage of adverse events
|
0.56 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Infections and infestations
|
15.91 Percentage of adverse events
|
8.33 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Injury, poisoning, procedural complications
|
0 Percentage of adverse events
|
0.56 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Investigations
|
6.82 Percentage of adverse events
|
20 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Metabolism and nutrition disorders
|
0 Percentage of adverse events
|
3.33 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Musculoskeletal, connective tissue disorders
|
0 Percentage of adverse events
|
4.44 Percentage of adverse events
|
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Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Nervous system disorders
|
4.55 Percentage of adverse events
|
5.00 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Psychiatric disorders
|
0 Percentage of adverse events
|
0.56 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Renal and urinary disorders
|
0 Percentage of adverse events
|
7.78 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Reproductive system and breast disorder
|
6.82 Percentage of adverse events
|
1.11 Percentage of adverse events
|
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Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Respiratory, thoracic, mediastinal disorders
|
2.27 Percentage of adverse events
|
9.44 Percentage of adverse events
|
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Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Skin and Subcutaneous disorders
|
25.0 Percentage of adverse events
|
6.11 Percentage of adverse events
|
|
Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients
Vascular disorders
|
0 Percentage of adverse events
|
1.67 Percentage of adverse events
|
Adverse Events
Sirolimus and Hydroxychloroquine 200 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Sirolimus and Hydroxychloroquine 400 mg
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sirolimus and Hydroxychloroquine 200 mg
n=3 participants at risk
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily.
|
Sirolimus and Hydroxychloroquine 400 mg
n=10 participants at risk
Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day.
|
|---|---|---|
|
Nervous system disorders
radiculitis
|
0.00%
0/3 • 48 weeks
|
10.0%
1/10 • Number of events 1 • 48 weeks
|
Other adverse events
| Measure |
Sirolimus and Hydroxychloroquine 200 mg
n=3 participants at risk
This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily.
|
Sirolimus and Hydroxychloroquine 400 mg
n=10 participants at risk
Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day.
|
|---|---|---|
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Skin and subcutaneous tissue disorders
Rash/ Acne
|
100.0%
3/3 • 48 weeks
|
50.0%
5/10 • 48 weeks
|
|
Investigations
Abnormal Investigations
|
33.3%
1/3 • 48 weeks
|
60.0%
6/10 • 48 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
66.7%
2/3 • 48 weeks
|
60.0%
6/10 • 48 weeks
|
|
Gastrointestinal disorders
Oral Mucositis
|
66.7%
2/3 • 48 weeks
|
60.0%
6/10 • 48 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place