Imatinib for LAM

(LAMP-2 Trial)

Recruiting at 1 trial location

Overseen By Sabrina Palumbo, BS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Columbia University

Must not be taking: Antifungals, Antibiotics, Analgesics, others

Disqualifiers: Transplant, Surgery, Pregnancy, others

Compensation: Varies

Number of Visits: 5

Duration: 6 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of imatinib mesylate, a drug approved for leukemia, to determine its potential in treating lymphangioleiomyomatosis (LAM), a rare lung disease. Researchers aim to understand how imatinib might kill LAM cells. Participants will receive either the drug or a placebo (a non-active treatment) over six months. This trial suits women aged 18-64 diagnosed with LAM who meet specific lung function criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to participate in this trial. Specifically, if you are taking any antifungal medications, certain antibiotics, migraine treatments, HIV medications, anti-seizure drugs, some antidepressants, targeted cancer drugs, or other specified medications, you will not be eligible to join the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that imatinib mesylate, a drug approved for treating leukemia, might also benefit those with Lymphangioleiomyomatosis (LAM), a rare lung disease. A previous small study, funded by the Department of Defense, assessed the safety of imatinib in LAM patients. This study found that imatinib was safe, even when combined with other treatments like mTOR inhibitors.

Although the earlier study was brief, it did not identify any major safety issues with imatinib. It is important to note that the current trial is in an early stage, focusing primarily on ensuring the treatment's safety for participants. This stage typically involves a small number of participants, allowing researchers to observe how well individuals tolerate the treatment and identify potential side effects. If imatinib had not already been used safely for another condition like leukemia, it might not have reached this trial stage.

For those considering joining the trial, this information may provide reassurance that imatinib has been used safely before, although each new study aims to gather more insights. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Imatinib Mesylate is unique because it targets a specific protein called PDGF receptor, which is thought to play a role in the growth of abnormal lung cells in Lymphangioleiomyomatosis (LAM). Unlike the standard treatments for LAM, such as sirolimus, which primarily work by inhibiting a different protein pathway called mTOR, imatinib offers a novel approach by directly interfering with another key pathway involved in the disease progression. Researchers are excited about imatinib because it has the potential to provide an alternative or complementary option to current therapies, possibly improving outcomes for patients who do not fully respond to existing treatments.

What evidence suggests that imatinib mesylate might be an effective treatment for LAM?

Research has shown that imatinib mesylate might help treat Lymphangioleiomyomatosis (LAM) by inducing the death of LAM cells. This is encouraging because LAM behaves like a slow-growing cancer in the lungs. Imatinib is already approved for certain types of leukemia, demonstrating its effectiveness in other conditions. A small study, LAMP-1, found that using imatinib in LAM patients was safe and influenced an important LAM marker called VEGF-D. In this trial, participants will receive either imatinib mesylate or a placebo. These early results suggest that imatinib could be a helpful treatment for LAM. ^{1 2 5 6 7}

Who Is on the Research Team?

Jeanine D'Armiento, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for individuals with a rare lung disease called Lymphangioleiomyomatosis (LAM). Participants must have been previously treated with sirolimus, as the study examines the effects of Imatinib Mesylate, a drug used in leukemia treatment that may cause LAM cell death. The trial involves office visits and bi-weekly phone check-ups over 6 months.

Inclusion Criteria

Able and willing to comply with the study procedures

I am a woman aged between 18 and 64.

My lung function tests show specific levels of breathing capacity.

Exclusion Criteria

I am a woman scheduled for surgery.

Dementia or other cognitive dysfunction that would prevent the participant from consenting to the study or completing study procedures

Non English speaking, illiterate, or other vulnerable persons

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive imatinib mesylate or placebo over the course of the trial

6 months

5 visits (in-person), check-up phone calls every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for long-term safety and changes in biomarkers

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Imatinib Mesylate

Trial Overview The study tests the long-term safety and tolerability of Imatinib Mesylate compared to a placebo in treating LAM. It follows up on earlier research suggesting benefits from this medication. Over six months, participants will receive either Imatinib or a placebo while their health is closely monitored.

How Is the Trial Designed?

Group I: Imatinib Mesylate Group Active Control 1 Intervention

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

Group II: Placebo Group Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

Imatinib mesylate, a tyrosine kinase inhibitor used for treating chronic myeloid leukemia and gastrointestinal stromal tumors, is generally well-tolerated, with most patients experiencing only mild side effects (grade 1 or 2).

Approximately 30% of patients on imatinib develop skin toxicity, with 5% experiencing high-grade reactions, including cases of extensive skin hyperpigmentation, which is linked to the drug's effect on melanocytes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpigmentation due to imatinib: A rare case of cutaneous involvement. Rehman, H., Hakim, N., Sugarman, R., et al.[2020]

In a study of 310 chronic myeloid leukemia (CML) patients treated with imatinib mesylate (400 mg/day), the most common adverse drug reactions (ADRs) were mild to moderate, with anemia being the most frequent hematological ADR and hyperpigmentation and nausea as the most common non-hematological ADRs.

The findings suggest that imatinib mesylate is a well-tolerated treatment for CML, with very few severe ADRs reported among patients in the chronic stable phase of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of adverse drug reactions of imatinib in chronic myeloid leukemia patients: An Eastern Indian experience. Swain, TR., Goutam, S., Jena, RK., et al.[2023]

Imatinib mesylate (IM) is an effective first-line treatment for chronic myeloid leukemia (CML) that works by inhibiting the bcr-abl fusion protein, but it can cause mild side effects like nausea and muscle cramps.

In some patients, IM can lead to significant skin reactions, such as photoinduced dermatitis and oral lichenoid reactions, which may require discontinuation of the drug or treatment with steroids, highlighting the need for monitoring skin changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate. Brazzelli, V., Muzio, F., Manna, G., et al.[2017]

In a study of 6 children with chronic myelogenous leukemia (CML) treated with imatinib mesylate for a median of 78.5 months, growth velocity was initially suppressed but improved over time, indicating a potential long-term recovery in growth despite early treatment effects.

The study found that 33.3% of patients had decreased bone mineral density (BMD), which was associated with longer imatinib exposure, and highlighted a high prevalence of vitamin D insufficiency, suggesting that vitamin D supplementation could be beneficial for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of imatinib in children with chronic myelogenous leukemia. Choeyprasert, W., Yansomdet, T., Natesirinilkul, R., et al.[2017]

Imatinib mesylate, a drug used to treat chronic myeloid leukemia, may be linked to ischemic maculopathy, which can lead to significant vision problems, as demonstrated in a case study of a 62-year-old woman.

The patient developed severe visual impairment and retinal abnormalities after starting imatinib therapy, highlighting the need for careful monitoring of patients for visual symptoms while on this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macular ischemia associated with imatinib mesylate therapy for chronic myeloid leukemia. Roth, DB., Akbari, S., Rothstein, A.[2014]

In a study of 92 children and adolescents with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the addition of imatinib to intensive chemotherapy significantly improved 3-year event-free survival (EFS) to 80%, compared to historical controls at 35%.

The study found that adding imatinib did not increase toxicity compared to chemotherapy alone, and that the combination treatment was as effective as blood and marrow transplantation (BMT) in terms of EFS, suggesting a potential alternative to BMT for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. Schultz, KR., Bowman, WP., Aledo, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06889168

Evaluating the Long-term Safety and Tolerability of Imatinib ... A large National Institute of Health study called MILES showed that sirolimus (also known as Rapamycin) improved lung function in individuals with LAM. Since ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06889168/evaluating-the-long-term-safety-and-tolerability-of-imatinib-in-patients-with-lymphangioleiomyomatosis-lam

Evaluating the Long-term Safety and Tolerability of Imatinib ... Recently, imatinib mesylate has been shown to induce LAM cell apoptosis, raising the possibility of more lasting therapy for LAM. Currently, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10713282/

Lymphangioleiomyomatosis and mTOR inhibitors in real ... We searched multiple reports and investigational studies regarding LAM, especially the therapeutic achievement won by mTOR inhibitors.

4. withpower.com withpower.com/trial/phase-1-lymphangioleiomyomatosis-3-2025-49b48

Imatinib for LAM (LAMP-2 Trial) Imatinib Mesylate is known to be effective in treating certain types of leukemia, such as chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), ...

5. trials.tscalliance.org trials.tscalliance.org/trials/NCT06889168

Evaluating the Long-term Safety and Tolerability of Imatinib in ... Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

6. trialx.com trialx.com/clinical-trials/listings/296038/evaluating-the-long-term-safety-and-tolerability-of-imatinib-in-patients-with-lymphangioleiomyomatosis-lam/

Evaluating the Long-term Safety and Tolerability of Imatinib ... Laboratory studies suggested that Imatinib mesylate (imatinib), an FDA-approved drug for leukemia, initiates LAM cell death. A pilot trial with ...

7. apps.dtic.mil apps.dtic.mil/sti/citations/AD1031112

LAM Pilot Study with Imatinib Mesylate (LAMP 1) - DTIC This pilot trial employs a dual agent design intended to generate safety and efficacy data sufficient to power and design a phase 3 study of imatinib vs placebo ...