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

NCT06889168 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAT1955
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Lymphangioleiomyomatosis; Lymphangioleiomyomatosis (LAM)

Keywords

LAM; LAMP-2; Imatinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in VEGF-D between study groups

  Baseline, 6 months

• Change in Forced Vital Capacity (FVC) between study groups

  Baseline, 6 months

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

  Baseline, 6 months

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

  Baseline, 6 months

Other Outcomes (5)

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

  1 year

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

  1 year

• Change in Modified Medical Research Council (mMRC) Dyspnea Score

  1 year

Study Arms (2)

Imatinib Mesylate Group

ACTIVE COMPARATOR

This group will receive imatinib mesylate over the course of the trial.

Drug: Imatimib Mesylate

Placebo Group

PLACEBO COMPARATOR

This group will receive placebo over the course of the trial.

Drug: Placebo

Interventions

Imatimib Mesylate DRUG

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

Also known as: Gleevec®, imatinib

Imatinib Mesylate Group

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.

Placebo Group

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• United States Department of Defense: collaborator
• Medical University of South Carolina: collaborator
• Columbia University: lead

Study Sites (2)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Lymphangiomyoma; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Perivascular Epithelioid Cell Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Jeanine D'Armiento, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katarina Koumbourlis, BS

CONTACT

212-305-3745; kk3922@cumc.columbia.edu

Sabrina Palumbo, BS

CONTACT

212-305-3745; sp4461@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is double-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine in Anesthesiology

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: March 21, 2025
• Study Start: October 20, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

US (2)