Boston, Massachusetts 02120

  • Lymphangioleiomyomatosis

Purpose:

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.


Study 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.


Criteria:

Inclusion Criteria: - Female age 18 or older - Ability to give informed consent - Diagnosis of LAM as defined as typical cystic change on CT plus: - biopsy or cytology of any tissue demonstrating LAM - angiomyolipoma, chylothorax, lymphangioleiomyoma, or tuberous sclerosis - serum VEGFD greater or equal to 800pg/ml - Post-bronchodilator FEV1 equal or less than 80% of predicted or DLCO equal equal or less than 70% of predicted, or RV > 120% of predicted at baseline - Women of childbearing potential must agree to use 2 forms of barrier contraception during and for 8 weeks after the last dose of medication. Exclusion Criteria: - History of intolerance of mTOR inhibitors - History of intolerance to hydroxychloroquine - History of severe psoriasis - History of porphyria cutanea tarda - Uncontrolled intercurrent illness - Pregnant, breast feeding, or plan to become pregnant in the next year - Inadequate contraception - Significant hematological or hepatic abnormalities - Use of an investigational drug within 30 days of study start - Inability to attend scheduled clinic visits - Inability to perform PFTs - Creatinine > 2.5mg/dL - Recent pneumothorax within 8 weeks of screening - History of malignancy in the last 2 years other than basal cell skin cancer - Use of estrogen containing medication within 30 days of screening - Abnormal G6PD levels at baseline - Preexisting maculopathy or retinopathy - Preexisting myopathy - Currently taking doxycycline, metformin, lupron, simvastatin - Unable to undergo CT or MRI - History of seizure within last year - Hepatitis B, C, HIV positive serology - Use of alternative medical therapies for LAM for at least 6 weeks prior to study participation - History of myocardial infarct, angina, or stroke related to atherosclerosis - History of cardiomyopathy - Previous lung transplant - Surgery (involving entry into a body cavity or requiring 3 or more stitches) within 2 months of initiation of study drug - Uncontrolled cholesterol > 350mg/dL, triglycerides > 400mg/dL


NCT ID:

NCT01687179


Primary Contact:

Principal Investigator
Elizabeth P Henske, MD
Brigham and Women's Hospital


Backup Contact:

N/A


Location Contact:

Boston, Massachusetts 02120
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: June 23, 2021

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