Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis (SAIL)
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|ClinicalTrials.gov Identifier: NCT01687179|
Recruitment Status : Completed
First Posted : September 18, 2012
Results First Posted : October 11, 2018
Last Update Posted : October 11, 2018
Specific Aim 1: To investigate whether, in Lymphangioleiomyomatosis (LAM) patients, the combination of sirolimus and hydroxychloroquine is safe and well tolerated
Specific Aim 2: To investigate whether, in LAM patients, 6 months of combination therapy with sirolimus and hydroxychloroquine results in improvement of indicators of disease, and whether the gains are sustained after stopping therapy.
Specific Aim 3: To investigate the potential role of a LAM-specific peripheral blood signature to predict rates of disease progression and determine responsiveness to combination therapy.
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. Up to 18 adult women with LAM will be enrolled.
|Condition or disease||Intervention/treatment||Phase|
|Lymphangioleiomyomatosis||Drug: "Sirolimus" and "Hydroxychloroquine" 200 mg Drug: "Sirolimus" and "Hydroxychloroquine" 400 mg||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus|
|Study Start Date :||September 2012|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||August 2015|
Experimental: "Sirolimus" and "Hydroxychloroquine"
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 for 6 months. Once safety is established at the lower dose ("Sirolimus" and "Hydroxychloroquine" 200 mg), subjects enrolled henceforth will receive Sirolimus and Hydroxychloroquine 400 mg (200 mg twice a day) for 6 months.
Drug: "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.
Other Name: sirolimus(rapamune), hydroxychloroquine (plaquenil)
Drug: "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.
Other Name: Sirolimus (Rapamune), Hydroxychloroquine (plaquenil)
- Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients [ Time Frame: 48 weeks ]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".
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01687179
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02120|
|Principal Investigator:||Elizabeth P Henske, MD||Brigham and Women's Hospital|
|Principal Investigator:||Joel Moss, MD, PhD||National Heart, Lung, and Blood Institute (NHLBI)|