LAM Pilot Study With Imatinib Mesylate (LAMP-1)
Primary Purpose
Lymphangioleiomyomatosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Imatinib Mesylate 400Mg Capsule
Placebo - Capsule
Sponsored by
About this trial
This is an interventional treatment trial for Lymphangioleiomyomatosis focused on measuring VEGF-D, Imatinib mesylate, Sirolimus
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.
Sites / Locations
- Columbia University
- Medical University of South Carolina
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Imatinib Mesylate 400mg capsule
Placebo Capsule
Arm 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.
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Outcomes
Primary Outcome Measures
Serum VEGF-D
Change in the square root of the intrasubject plasma VEGF-D
Secondary Outcome Measures
Adverse Events
Adverse event and Serious Adverse Event numbers using the CTCAE Version 4.03 definitions
Full Information
NCT ID
NCT03131999
First Posted
April 24, 2017
Last Updated
June 4, 2020
Sponsor
Medical University of South Carolina
Collaborators
Columbia University
1. Study Identification
Unique Protocol Identification Number
NCT03131999
Brief Title
LAM Pilot Study With Imatinib Mesylate
Acronym
LAMP-1
Official Title
LAM Pilot Study With Imatinib Mesylate
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
January 23, 2018 (Actual)
Primary Completion Date
March 7, 2019 (Actual)
Study Completion Date
March 7, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of South Carolina
Collaborators
Columbia University
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphangioleiomyomatosis
Keywords
VEGF-D, Imatinib mesylate, Sirolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imatinib Mesylate 400mg capsule
Arm Type
Experimental
Arm 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.
Arm Title
Placebo Capsule
Arm Type
Placebo Comparator
Arm Description
56 days of Placebo with or without co-administration of an mTOR inhibitor for 28 days. A dose reduction is allowed for toxicity.
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate 400Mg Capsule
Other Intervention Name(s)
Gleevec
Intervention Description
Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
Intervention Type
Drug
Intervention Name(s)
Placebo - Capsule
Other Intervention Name(s)
Placebo
Intervention Description
Sirolimus or everolimus will be withdrawn after 28 days if used at baseline
Primary Outcome Measure Information:
Title
Serum VEGF-D
Description
Change in the square root of the intrasubject plasma VEGF-D
Time Frame
Before and 1 month after initiation of monotherapy imatinib mesylate or placebo
Secondary Outcome Measure Information:
Title
Adverse Events
Description
Adverse event and Serious Adverse Event numbers using the CTCAE Version 4.03 definitions
Time Frame
3 months
Other Pre-specified Outcome Measures:
Title
Lung Function
Description
FEV1 % predicted change
Time Frame
2 months
Title
SGRQ
Description
Saint Georges Respiratory Questionnaire change
Time Frame
2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Meinberg
Organizational Affiliation
Congressionally Directed Medical Research Programs
Official's Role
Study Director
Facility Information:
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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LAM Pilot Study With Imatinib Mesylate
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