LAM Pilot Study With Imatinib Mesylate (LAMP-1)

• ClinicalTrials.gov Identifier: NCT03131999
• Recruitment Status: Completed
• First Posted: April 27, 2017
• Results First Posted: March 26, 2020
• Last Update Posted: June 16, 2020
• Sponsor: Medical University of South Carolina
• Collaborator: Columbia University
• Information provided by (Responsible Party): Charlie Strange, Medical University of South Carolina

Tracking Information

• First Submitted Date: April 24, 2017
• First Posted Date: April 27, 2017
• Results First Submitted Date: February 25, 2020
• Results First Posted Date: March 26, 2020
• Last Update Posted Date: June 16, 2020
• Actual Study Start Date: January 23, 2018
• Actual Primary Completion Date: March 7, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2017)

Serum VEGF-D [ Time Frame: Before and 1 month after initiation of monotherapy imatinib mesylate or placebo ]

Change in the square root of the intrasubject plasma VEGF-D

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 25, 2020)

Adverse Events [ Time Frame: 3 months ]

Adverse event and Serious Adverse Event numbers using the CTCAE Version 4.03 definitions

Original Secondary Outcome Measures (submitted: April 24, 2017)

Adverse events [ Time Frame: 3 months ]

Adverse event and Serious Adverse Event numbers using the CTCAE Version 4.03 definitions

Current Other Pre-specified Outcome Measures (submitted: February 25, 2020)

• Lung Function [ Time Frame: 2 months ]
  FEV1 % predicted change
• SGRQ [ Time Frame: 2 months ]
  Saint Georges Respiratory Questionnaire change

Original Other Pre-specified Outcome Measures (submitted: April 24, 2017)

• Lung function [ Time Frame: 2 months ]
  FEV1 % predicted change
• SGRQ [ Time Frame: 2 months ]
  Saint Georges Respiratory Questionnaire change

Descriptive Information

• Brief Title: LAM Pilot Study With Imatinib Mesylate
• Official Title: LAM Pilot Study With Imatinib Mesylate
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Lymphangioleiomyomatosis

Intervention

• Drug: Imatinib Mesylate 400Mg Capsule
  Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
  Other Name: Gleevec
• Drug: Placebo - Capsule
  Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
  Other Name: Placebo

Study Arms

• Experimental: 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.
  Intervention: Drug: Imatinib Mesylate 400Mg Capsule
• Placebo Comparator: 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.
  Intervention: Drug: Placebo - Capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 16, 2019): 18
• Original Estimated Enrollment (submitted: April 24, 2017): 20
• Actual Study Completion Date: March 7, 2019
• Actual Primary Completion Date: March 7, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03131999
• Other Study ID Numbers: PRO00044389
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Charlie Strange, Medical University of South Carolina
• Original Responsible Party: Same as current
• Current Study Sponsor: Medical University of South Carolina
• Original Study Sponsor: Same as current
• Collaborators: Columbia University

Investigators

• Study Director: Christopher Meinberg; Congressionally Directed Medical Research Programs

• PRS Account: Medical University of South Carolina
• Verification Date: June 2020