LAM Pilot Study With Imatinib Mesylate

LAM Pilot Study With Imatinib Mesylate

This is a phase 1 clinical trial comparing imatinib mesylate to placebo for individuals with lymphangioleiomyomatosis (LAM).

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.