Evaluating the Long-term Safety and Tolerability of Imatinib in Patients With Lymphangioleiomyomatosis (LAM)

ConditionsLymphangioleiomyomatosis (LAM)Lymphangioleiomyomatosis

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexFemale

Age18-64

SponsorColumbia University

About this trial

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that appears to behave like a slowly growing cancer. Since clinical progression is very slow, new blood tests have been used to speed the time required to find safe and effective medications. A large National Institute of Health study called MILES showed that sirolimus (also known as Rapamycin) improved lung function in individuals with LAM. Since most individuals with LAM and impaired lung function are now on sirolimus, future studies may prove more difficult. Laboratory studies suggested that Imatinib mesylate (imatinib), an FDA-approved drug for leukemia, initiates LAM cell death. A pilot trial with imatinib titled "Imatinib Mesylate for the treatment of Lymphangioleiomyomatosis" - (LAMP-1) was funded by the Department of Defense in 2016, and documented (1) the safety of use of tyrosine kinase inhibitors in patients with LAM; (2) the safety of concurrent use of tyrosine kinase and mTOR inhibitors; and, (3) short term variability in vascular endothelial growth factor D (VEGF-D) - a LAM biomarker, as a response to therapies. Due to the short-term LAMP-1 trial, LAMP-2 will be a longer-term 6-month clinical study evaluating the safety and tolerability of imatinib in patients with LAM. Patients that participate in the trial will come in for 5 office visits and check-up phone calls every 2 weeks over the course of 6 months.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Women 18 through 64 years of age (inclusive)

DLCO >20% predicted and FVC <90% OR

Post bronchodilator FEV1 between 30% and 90% predicted.

Confirmed or possible diagnosis of LAM

Disqualifiers

Women who have or will undergo a transplant

Women who will undergo surgery

Women who are currently pregnant or plan on a pregnancy

Women who are currently breast feeding or lactating

Trial design

Design model

Parallel

Treatments tested in this trial

Imatimib Mesylate
Drug
Participants will take Imatinib mesylate (imatinib), an FDA approved drug for leukemia, orally 400 mg (twice daily)
Placebo
Drug
Placebo will be administered in the same dosage and manner as the study drug. The placebo looks like the study drug but contains no active ingredients.

Treatment groups

20 Participants

are divided into 2 treatment groups

Group A: Imatinib Mesylate GroupActive comparator 1 intervention

Group B: Placebo GroupPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

Incidence of Adverse Events

To observe and compare the occurrence of adverse events experienced by participants receiving imatinib mesylate compared to placebo throughout the duration of the study.

Time frame

1 year

Secondary outcomes

Change in VEGF-D between study groups

To compare the change in the log-transformed level of VEGF-D from baseline to 6 months between imatinib mesylate and placebo groups.

Time frame

Baseline, 6 months

Change in Forced Vital Capacity (FVC) between study groups

To compare the change in Forced Vital Capacity (FVC) from baseline to 6 months between imatinib mesylate and placebo groups.

Time frame

Baseline, 6 months

Change in percent Forced Expiratory Volume in One Second (FEV1) between study groups

To compare the change in the percent predicted FEV1 (Forced expiratory volume in one second) using "GLI other" standards from baseline to 6 months between imatinib mesylate and placebo groups.

Time frame

Baseline, 6 months

Change in St. George Respiratory Questionnaire (SGRQ) score between study groups

To compare the change in the total score of the St. George Respiratory Questionnaire (SGRQ) from baseline to 6 months between imatinib mesylate and placebo groups. Scores range from 0 to 100, with 0 representing no health impairment and 100 representing maximum health impairment.

Time frame

Baseline, 6 months

Other outcomes

Change in High Mobility Group AT-Hook2 (HMGA2) between study groups

To compare the change in expression of the neural crest biomarker HMGA2 (High Mobility Group AT-Hook2) between imatinib and placebo groups in the entire group, and in those not on sirolimus.

Time frame

1 year

Change in percent Forced Expiratory Volume in One Second (FEV1)

To compare the change in the percent predicted FEV1 between imatinib and placebo groups in those not on sirolimus.

Time frame

1 year

Change in Modified Medical Research Council (mMRC) Dyspnea Score

To compare the change in mMRC (Modified Medical Research Council) Dyspnea score between imatinib and placebo groups in the entire group and in those not on sirolimus. The mMRC scale is a self-rating tool to measure the degree of disability that breathlessness poses on day-to-day activities on a scale from 0 to 4. A higher score indicates a higher degree of disability due to breathlessness.

Time frame

1 year

Change in 6 Minute Walk Test (6MWT)

To compare the change in the 6MWT (6 Minute Walk Test) distance between imatinib and placebo groups in the entire group and in those not on sirolimus. The 6MWT measures how far a participant can walk in 6 minutes.

Time frame

1 year

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Columbia University

Lead sponsor

United States Department of Defense

Collaborator

Medical University of South Carolina

Collaborator

Source ClinicalTrials.gov

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