LAM Pilot Study With Imatinib Mesylate (LAMP-1)

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

Study Overview

• Status: Completed
• Conditions: Lymphangioleiomyomatosis
• Intervention / Treatment: Drug: Imatinib Mesylate 400Mg Capsule; Drug: Placebo - Capsule

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
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Imatinib Mesylate 400Mg Capsule; Sirolimus or everolimus will be withdrawn after 28 days if used at baseline; Other Names: Gleevec
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.	Drug: Placebo - Capsule; Sirolimus or everolimus will be withdrawn after 28 days if used at baseline; Other Names: Placebo

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Function	FEV1 % predicted change	2 months
SGRQ	Saint Georges Respiratory Questionnaire change	2 months

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Columbia University
• Investigators: Study Director: Christopher Meinberg, Congressionally Directed Medical Research Programs

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2018
• Primary Completion (Actual): March 7, 2019
• Study Completion (Actual): March 7, 2019

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Sirolimus; Imatinib mesylate; VEGF-D
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphangiomyoma; Lymphatic Vessel Tumors; Perivascular Epithelioid Cell Neoplasms; Lymphangioleiomyomatosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: PRO00044389

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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