Clinical Trial: Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus

Brief Summary:

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.


Detailed Summary: 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.
Sponsor: Brigham and Women's Hospital

Current Primary Outcome: safety of everolimus and hydroxychloroquine [ Time Frame: 4 years ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Brigham and Women's Hospital

Dates:
Date Received: August 2, 2012
Date Started: September 2012
Date Completion:
Last Updated: August 11, 2016
Last Verified: August 2016