NCT01687179

Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: Female
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

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 description

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.

Conditions

• Lymphangioleiomyomatosis

Interventions

Type	Name	Description
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.
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.

Timeline

• Start date: 2012-09-01
• Primary completion: 2015-08-01
• Completion: 2015-08-01
• First posted: 2012-09-18
• Last updated: 2018-10-11
• Results posted: 2018-10-11

Locations

1 site across 1 country: United States