Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus
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 for 6 months. The study is to be conducted at 2 sites. Up to 18 adult women
with LAM will be enrolled, and each recruiting site will recruit between 8-12 subjects. The
protocol will use the following eligibility criteria.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
safety of everolimus and hydroxychloroquine
We will conduct a two-center phase I trial of sirolimus (mTOR inhibitor) in combination with hydroxychloroquine (autophagy inhibitor 200-400mg) administered daily for 24 weeks. Eligible subjects will receive 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 design. All adverse events will be captured.
Elizabeth P Henske, MD
Brigham and Women's Hospital
United States: Federal Government
|Brigham and Women's Hospital||Boston, Massachusetts 02115|