Efficacy and Safety of Sirolimus in LAM

Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that is caused by genetic mutations. It results in the uncontrolled growth of an unusual type of smooth muscle cell in the lung. These cells invade lung tissue, including the airways, blood vessels, and lymph vessels, and restrict the flow of air, blood, and lymph, respectively. Respiratory failure, lung collapse (pneumothorax), and pleural effusions (chylothorax) are hallmarks of the disease. This study will evaluate the safety and effectiveness of sirolimus, an inhibitor of the mTOR pathway, in stabilizing or improving lung function in people with LAM.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* Age 18 or older
* Signed and dated informed consent
* Diagnosis of LAM based on compatible chest CT scan and a) biopsy or cytology consistent with LAM, or b) presence of tuberous sclerosis, angiomyolipoma or chylous pleural effusion; or c) a VEGF-D level of at least 800 pg/ml
* Forced expiratory volume in one second (FEV1) of 70% or less of predicted value after administration of a bronchodilator

Exclusion Criteria:

* Known allergy to sirolimus
* History of heart attack, angina, or stroke due to clogging, narrowing, and hardening of the arteries and blood vessels
* Significant hematologic or hepatic abnormality (transaminase levels greater than three times the upper limit of normal, HCT less than 30%, platelets less than 80,000/cubic mm, adjusted absolute neutrophil count less than 1,000/cubic mm, total white blood cell count less than 3,000/cubic mm)
* Intercurrent infection at the time treatment with sirolimus begins
* Any surgery involving entry into a body cavity or requiring three or more sutures within 8 weeks of initiation of study drug
* Use of an investigational drug within the 30 days prior to random assignment
* Uncontrolled hyperlipidemia
* Previous lung transplant or currently on lung transplant list
* Unable to attend scheduled study visits
* Unable to perform pulmonary function tests
* Creatinine levels greater than 2.5 mg/dl
* Chylous ascites severe enough to affect diaphragmatic function
* Pleural effusion severe enough to affect pulmonary function, as determined by the study physician
* History of acute pneumothorax within the 2 months prior to study entry
* History of malignancy within the 2 years prior to study entry (except for squamous or basal cell skin cancer)
* Use of estrogen containing medication within the thirty days prior to randomization
* Unable or unwilling to use adequate contraception
* Pregnant, breastfeeding, or plans to become pregnant within the next 2 years

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