LAM Pilot Study With Imatinib Mesylate

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

Detailed Description
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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.

Official Title
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LAM Pilot Study With Imatinib Mesylate

Conditions
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Lymphangioleiomyomatosis

Intervention / Treatment
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* Drug: Imatinib Mesylate 400Mg Capsule
* Drug: Placebo - Capsule


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib Mesylate 400mg capsule<br>56 days of Imatinib mesylate 400 mg oral daily with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction to 200 mg daily is allowed for toxicity. | Drug: Imatinib Mesylate 400Mg Capsule<br>* Sirolimus or everolimus will be withdrawn after 28 days if used at baseline<br>* Other names: Gleevec;|
| Placebo Comparator: Placebo Capsule<br>56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity. | Drug: Placebo - Capsule<br>* Sirolimus or everolimus will be withdrawn after 28 days if used at baseline<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum VEGF-D | Change in the square root of the intrasubject plasma VEGF-D | Before and 1 month after initiation of monotherapy imatinib mesylate or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Adverse event and Serious Adverse Event numbers using the CTCAE Version 4.03 definitions | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VEGF-D, Imatinib mesylate, Sirolimus