RecruitingPhase 1NCT06889168

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

A Phase 1, Randomized, Double-blinded, Placebo Controlled, Trial Evaluating the Long-term Safety and Tolerability of Imatinib for the Treatment of Lymphangioleiomyomatosis [LAMP-2 Trial]

Sponsor

Columbia University

Enrollment

20 participants

Start Date

Oct 20, 2025

Study Type

INTERVENTIONAL

Conditions

Lymphangioleiomyomatosis Lymphangioleiomyomatosis (LAM)

Summary

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

Sex: FEMALEMin Age: 18 YearsMax Age: 64 Years

Inclusion Criteria7

Women 18 through 64 years of age (inclusive)
Pulmonary Function Test (PFT) with following criteria:
DLCO >20% predicted and FVC <90% OR
Post bronchodilator FEV1 between 30% and 90% predicted.
Confirmed or possible diagnosis of LAM
Willing to avoid grapefruit juice and St. John's wort while in the study
Able and willing to comply with the study procedures

Exclusion Criteria16

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
Dementia or other cognitive dysfunction that, in the opinion of the investigator, would prevent the participant from consenting to the study or completing study procedures
Currently taking any of the following medications:
Antifungal Medications: Ketoconazole; Itraconazole ; Voriconazole.
Antibiotics for bacterial infections: Clarithromycin.
Analgesics to treat headaches/migraines: Dihydroergotamine; Dihydroergotamine intranasal
Antiretroviral protease inhibitors used in human immunodeficiency virus (HIV) infections: Atazanavir ; Nelfinavir; Indinavir; Ritonavir; Saquinavir
Anti-epileptic or seizure medications: Carbamazepine, Fosphenytoin; Oxcarbamazepine; Phenobarbital ; Phenytoin; Primidone
Anti-depressant medications: Nefazodone; St. John's wort
Targeted cancer drugs: Regorafenib; Venetoclax ; Cobimetinib
Ivabradine (used to treat chronic heart failure); Telithromycin (used to treat community acquired pneumonia); Lomitapide (treatment of familial hypercholesterolemia); Lonafarnib (Hutchinson-Gilford progeria syndrome); conivaptan (treat low sodium levels); flibanserin (management of hypoactive sexual desire disorder (HSDD)); Naloxegol (opioid-induced constipation); Warfarin (prevent blood clots); Lurasidone (schizophrenia and bipolar depression); Eliglustat (treatment of Gaucher's disease).
Non English speaking, illiterate, or other vulnerable persons will not be included among study subjects.
Any condition that in the opinion of the investigator might adversely influence the study outcome.

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Interventions

DRUGImatimib Mesylate

Participants will take Imatinib mesylate (imatinib), an FDA approved drug for leukemia, orally 400 mg (twice daily)

DRUGPlacebo

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.