LAM Pilot Study With Imatinib Mesylate (LAMP-1)

Medical University of South Carolina (MUSC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lymphangioleiomyomatosis

Treatments: Drug: Placebo - Capsule; Drug: Imatinib Mesylate 400Mg Capsule

Study type: Interventional

Funder types: Other

Identifiers

NCT03131999

PRO00044389

Details and patient eligibility

About

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

Full description

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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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18 participants in 2 patient groups, including a placebo group

Imatinib Mesylate 400mg capsule

Experimental group

Description:

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.

Treatment:

Drug: Imatinib Mesylate 400Mg Capsule

Placebo Capsule

Placebo Comparator group

Description:

56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.

Treatment:

Drug: Placebo - Capsule