Evaluating the Long-term Safety and Tolerability of Imatinib in Patients With Lymphangioleiomyomatosis (LAM)
Study Purpose
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.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
No
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
Interventional
Eligible Ages
18 Years - 64 Years
Gender
Female
More Inclusion & Exclusion Criteria
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-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.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Phase 1
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
Columbia University
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study.
Jeanine D'Armiento, MD, PhD
Principal Investigator Affiliation
Columbia University
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
Other, U.S. Fed
Overall Status
Recruiting
Countries
United States
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied.
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.
Arms & Interventions
Arms
Active Comparator: Imatinib Mesylate Group
This group will receive imatinib mesylate over the course of the trial.
Placebo Comparator: Placebo Group
This group will receive placebo over the course of the trial.
Interventions
Drug: - Imatimib Mesylate
Participants will take Imatinib mesylate (imatinib), an FDA approved drug for leukemia,
orally 400 mg (twice daily)
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.
Contact a Trial Team
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