LAM Pilot Study With Imatinib Mesylate

Phase 1

Completed

• Conditions: Lymphangioleiomyomatosis
• Interventions: Drug: Imatinib Mesylate 400Mg Capsule; Drug: Placebo - Capsule

• Registration Number: NCT03131999
• Lead Sponsor: Medical University of South Carolina

Brief Summary

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

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-04-24
• Study First Submitted QC: 2017-04-24
• Study First Posted: 2017-04-27
• Study Start: 2018-01-23
• Primary Completion: 2019-03-07
• Study Completion: 2019-03-07
• Results First Submitted: 2020-02-25
• Results First Submitted QC: 2020-03-13
• Results First Posted: 2020-03-26
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-04
• Last Update Posted: 2020-06-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Definite or Probable LAM
• FVC or Postbronchodilator FEV1 <90% predicted

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Imatinib Mesylate 400mg capsule	Imatinib Mesylate 400Mg Capsule	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.
Placebo Capsule	Placebo - Capsule	56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.

Primary Outcome Measures

Name	Time	Method
Serum VEGF-D	Before and 1 month after initiation of monotherapy imatinib mesylate or placebo	Change in the square root of the intrasubject plasma VEGF-D

Secondary Outcome Measures

Name	Time	Method
Adverse Events	3 months	Adverse event and Serious Adverse Event numbers using the CTCAE Version 4.03 definitions

Trial Locations

Locations (2)

Columbia University; 🇺🇸 New York, New York, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States