Evaluating the Long-term Safety and Tolerability of Imatinib in Patients With Lymphangioleiomyomatosis (LAM) (LAMP-2)

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]

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphangioleiomyomatosis (LAM); Lymphangioleiomyomatosis
• Intervention / Treatment: Drug: Imatimib Mesylate; Drug: Placebo

Detailed Description

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that is due to a very slow growing cancer that proliferates via unopposed activity of the mTOR pathway. A large NIH study (MILES) found that sirolimus (Rapamycin) that inhibits the mTOR pathway improved lung function and quality of life compared to placebo in LAM. Sirolimus has been shown to cause growth suppression but not apoptosis of LAM cells in culture. Additionally, not all patients with LAM have a clinical effect with sirolimus. Recently, imatinib mesylate has been shown to induce LAM cell apoptosis, raising the possibility of more lasting therapy for LAM. Currently, most LAM patients are on sirolimus and attempts to find sirolimus naive patients have not been successful for other studies. LAM cells use the mesenchymal PDGF receptor pathway for proliferation, similar to certain leukemias and slow growing neoplasms. Laboratory studies suggested that Imatinib mesylate (imatinib), an FDA approved drug for leukemia, initiates LAM cell death. A pilot trial with imatinib (LAMP-1) was funded by the DOD 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 VEGF-D as a response to therapies. Concurrent cell-based research studies during this time showed equally efficacious tumoricidal activity of nilotinib in vitro. Due to the short-term LAMP-1 trial, the investigators propose a longer-term clinical study evaluating the safety and tolerability of imatinib in patients with LAM.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sabrina Palumbo, BS; Phone Number: 212-305-3745; Email: sp4461@cumc.columbia.edu
• Study Contact Backup: Name: Katarina Koumbourlis, BS; Phone Number: 212-305-3745; Email: kk3922@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Principal Investigator: Jeanine D'Armiento, MD, PhD
      • Sub-Investigator: Monica Goldklang, MD
      • Contact: Sabrina Palumbo, BS; Phone Number: 212-305-3745; Email: sp4461@cumc.columbia.edu
      • Contact: Katarina Koumbourlis; Phone Number: 212-305-3745; Email: kk3922@cumc.columbia.edu
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Charlie Strange, MD
      • Contact: Seth Polk; Phone Number: 7573341517; Email: polkse@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women 18 through 64 years of age (inclusive)

• Pulmonary Function Test (PFT) with following criteria:

  1. DLCO >20% predicted and FVC <90% OR
  2. 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 Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Imatinib Mesylate Group; This group will receive imatinib mesylate over the course of the trial.	Drug: Imatimib Mesylate; Participants will take Imatinib mesylate (imatinib), an FDA approved drug for leukemia, orally 400 mg (twice daily); Other Names: Gleevec®; imatinib
Placebo Comparator: Placebo Group; This group will receive placebo over the course of the trial.	Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Baseline, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	1 year
Change in EuroQol 5 Dimension (EQ5D)	To compare the change in EQ5D scores between imatinib and placebo groups in the entire group and in those not on sirolimus. The EQ-5D (EuroQol 5 Dimension) is a questionnaire designed to measure a person's health-related quality of life by assessing their self-reported experiences across five key dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scoring is based on a scale of 0-100, 0 being the worst imaginable health state and 100 being the best imaginable health state.	1 year

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Medical University of South Carolina; United States Department of Defense
• Investigators: Principal Investigator: Jeanine D'Armiento, MD, PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 15, 2025
• First Submitted That Met QC Criteria: March 15, 2025
• First Posted (Actual): March 21, 2025

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Imatinib; LAM; LAMP-2
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Connective and Soft Tissue; Lymphangiomyoma; Perivascular Epithelioid Cell Neoplasms; Hemic and Lymphatic Diseases; Neoplasm, Lymphatic Tissue; Lymphangioleiomyomatosis; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Pyrimidines; Benzene Derivatives; Acids, Carbocyclic; Benzoates; Benzamides; Piperazines; Imatinib Mesylate
• Other Study ID Numbers: AAAT1955

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.: No