LAM Pilot Study With Imatinib Mesylate

This is a double blind, adjusted parallel design, randomized clinical trial comparing
imatinib mesylate 400 mg daily or matching placebo on the primary outcome of log transformed
serum VEGF-D level in patients with LAM.

Sirolimus using patients will have co-administration of Imatinib mesylate or placebo for 28
days prior to sirolimus discontinuation.

The duration of 400 mg imatinib mesylate or placebo will be 56 days, a dose reduction is
allowed for toxicity.

The primary endpoint will be the change in the log transformed VEGF-D one month after
monotherapy imatinib mesylate or placebo.

Total trial duration is 2 months of drug administration.

Inclusion Criteria:

- Definite or Probable LAM

- FVC or Postbronchodilator FEV1 <90% predicted

Exclusion Criteria:

- Current or planned pregnancy or lactation

- Unwillingness to discontinue sirolimus

- Change in the dose or use of sirolimus within the past month

- Inability to perform spirometry

- Allergy or intolerance of albuterol and/or ipratropium

- Other serious illness that would impact the outcome of the study including cancer that
has not received curative therapy, Grade III/IV cardiac problems as defined by the New
York Heart Association Criteria. (i.e., congestive heart failure, myocardial
infarction within 6 months of study), uncontrolled diabetes, chronic renal disease,
chronic liver disease, or active uncontrolled infection

- Current lung transplant

- Known diagnosis of human immunodeficiency virus (HIV) infection

- Current cigarette smoking

- Required use of warfarin, ketoconazole, itraconazole, clarithromycin, or rifampin
during the 2 months of the study.

- Unwillingness to avoid grapefruit juice or St. Johns Wort during the study.

- Planned surgery during the 2 months of the study.

- Patient with any significant history of non-compliance to medical regimens or with
inability to grant reliable informed consent.

- Patient has received and other investigational agents within 28 days of first day of
study drug dosing.