Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial

NCT03150914 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: RLDC5713U01HL131755-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 8

Brief Summary

This is a study to determine if early, long-term low dose sirolimus is effective for preventing progression to more advanced stages.

Conditions

LAM; Lymphangioleiomyomatosis

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in 1 Second (FEV1 slope)

  Rate of lung function decline

  2 years

Secondary Outcomes (2)

• Diffusing Capacity for Carbon Monoxide (DLCO)

  2 years

• Total Lung Capacity (TLC)

  2 years

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Overencapsulated matrix

Drug: Sirolimus

Treatment

ACTIVE COMPARATOR

Over-encapsulated 1 mg sirolimus tablet

Drug: Sirolimus

Interventions

Sirolimus DRUG

mTOR inhibitor or placebo

Also known as: Rapamycin

Placebo; Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, age 18 or over
• Signed and dated informed consent
• Diagnosis of LAM as determined by compatible lung CT and one of the following
• biopsy (lung, abdominal mass, lymph node or kidney) or cytology from thoracic or abdominal sources revealing LAM, or
• tuberous sclerosis, angiomyolipomata (diagnosed by CT, MRI by the site radiologist or biopsy) or chylous pleural effusion (verified by tap), or
• VEGF-D level ≥ 800 pg/ml.
• Post-bronchodilator forced expiratory volume in one second of \> 70%
• Presence of markers of non-trivial burden of LAM or likely progression based on one of the following:
• pretrial FEV 1 rate of decline of \>60cc/yr, comparing enrollment FEV1 to any prior measurement in the past 3 years, or
• baseline supplemental oxygen requirement with exercise, or
• pre-menopausal and one of the following (if post-menopausal, must have a VEGF-D level ≥ 600 pg/ml and one of the following) baseline diffusing capacity for carbon monoxide ≤80% predicted,
• a) baseline residual volume ≥120% predicted, b) baseline desaturation by 4% or more on six minute walk testing on room air c) more than 20 cysts on the carinal cut of the CT

You may not qualify if:

• Existing or imminent (within 12-18 months) clinical indication for treatment with mTOR inhibitors, based on judgment of site investigator
• DLCO \<60% predicted
• Resting room air saturation \<90%
• Exercise induced desaturation nadir on room air \< 85%
• History of myocardial infarction, angina or stroke related to atherosclerosis
• Pregnant, breast feeding, or plan to become pregnant in the next 2.5 years
• Inadequate contraception
• Significant hematologic, renal, metabolic or hepatic abnormality (i.e. transaminase levels \> three times the UL of normal range, HCT \< 30%, platelets \< 80,000/mm3, adjusted absolute neutrophil count \< 1,000/ mm3, total WBC \< 3,000/ mm3), creatinine \>2.5 mg/dl, uncontrolled hyperlipidemia
• Acute or chronic infection, such as (nontuberculous mucobacteria or active hepatitis B or C infections)
• Recent surgery (involving entry into a body cavity or requiring 3 or more sutures) within three weeks of initiation of study drug
• Use of sirolimus, everolimus or investigational treatment for LAM within the 30 days prior to randomization
• Previous lung transplantation or active on transplant list
• Inability to attend scheduled clinic visits, or perform pulmonary function testing
• Pleural effusion or chylous ascites sufficient to affect pulmonary function based on the opinion of the Site Investigator
• Acute pneumothorax within the past month

Sponsors & Collaborators

• University of Cincinnati: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• The LAM Foundation: collaborator

Study Sites (8)

Stanford University

Palo Alto, California, 94305, United States

Location

National Jewish Hospital

Denver, Colorado, 80206-2761, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Loyola University

Chicago, Illinois, 60153, United States

Location

Brigham and Woman's Hospital

Boston, Massachusetts, 20892, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45174, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Swedish Health

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Sirolimus

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)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Francis X. McCormack, M.D.

  University of Cincinnati

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Tablets are over-encapsulated. Both participant and care givers are blinded to treatment assignment. Dose adjustments for out of range sirolimus levels are made by a medical monitor at the Data Center. Sham dose adjustments are made in the placebo group
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Intention to treat, randomized, placebo controlled, double blind

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 12, 2017
• Study Start: January 1, 2018
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Estimated Spring 2026
• Access Criteria: After study completion and publication, deidentified data may be requested by an email to the PI, Frank McCormack, with a data use agreement between the University of Cincinnati and the requesting entity.

Locations

US (8)