Clinical trial NCT03131999: LAM Pilot Study With Imatinib Mesylate
Official title: LAM Pilot Study With Imatinib Mesylate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphangioleiomyomatosis
Keywords: VEGF-D
Imatinib mesylate
Sirolimus
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Columbia University
First posted: 2017-04-27
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Serum VEGF-D
timeFrame: Before and 1 month after initiation of monotherapy imatinib mesylate or placebo
Secondary outcomes:
measure: Adverse Events
timeFrame: 3 months
Other outcomes:
measure: Lung Function
timeFrame: 2 months
measure: SGRQ
timeFrame: 2 months
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Congressionally Directed Medical Research Programs
name: Christopher Meinberg
role: STUDY_DIRECTOR
References: