Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial

• Register: ClinicalTrials.gov
• Last refreshed on: 6 November 2023
• Main ID: NCT03150914
• Date of registration: 10/05/2017
• Prospective Registration: Yes
• Primary sponsor: University of Cincinnati
• Public title: Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial MILED
• Scientific title: Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial
• Date of first enrolment: January 1, 2018
• Target sample size: 60
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03150914
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Francis X. McCormack, M.D.
• Affiliation: University of Cincinnati

• Name: Susan McMahan Sellers, BSN, RN

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Female, age 18 or over

2. Signed and dated informed consent

3. Diagnosis of LAM as determined by compatible lung CT and one of the following

1. biopsy (lung, abdominal mass, lymph node or kidney) or cytology from thoracic or
abdominal sources revealing LAM, or

2. tuberous sclerosis, angiomyolipomata (diagnosed by CT, MRI by the site
radiologist or biopsy) or chylous pleural effusion (verified by tap), or

3. VEGF-D level = 800 pg/ml.

4. Post-bronchodilator forced expiratory volume in one second of > 70%

5. Presence of markers of non-trivial burden of LAM or likely progression based on one of
the following:

1. pretrial FEV 1 rate of decline of >60cc/yr, comparing enrollment FEV1 to any
prior measurement in the past 3 years, or

2. baseline supplemental oxygen requirement with exercise, or

3. 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

Exclusion Criteria:

1. Existing or imminent (within 12-18 months) clinical indication for treatment with mTOR
inhibitors, based on judgment of site investigator

2. DLCO <60% predicted

3. Resting room air saturation <90%

4. Exercise induced desaturation nadir on room air < 85%

5. History of myocardial infarction, angina or stroke related to atherosclerosis

6. Pregnant, breast feeding, or plan to become pregnant in the next 2.5 years

7. Inadequate contraception

8. 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

9. Acute or chronic infection, such as (nontuberculous mucobacteria or active hepatitis B
or C infections)

10. Recent surgery (involving entry into a body cavity or requiring 3 or more sutures)
within three weeks of initiation of study drug

11. Use of sirolimus, everolimus or investigational treatment for LAM within the 30 days
prior to randomization

12. Previous lung transplantation or active on transplant list

13. Inability to attend scheduled clinic visits, or perform pulmonary function testing

14. Pleural effusion or chylous ascites sufficient to affect pulmonary function based on
the opinion of the Site Investigator

15. Acute pneumothorax within the past month

16. History of malignancy in the past two years, other than squamous or basal cell skin
cancer.

17. Use of estrogen containing medications within the 30 days prior to randomization.

18. Known allergy to sirolimus



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

LAM

Lymphangioleiomyomatosis

Intervention(s)

Drug: Sirolimus

Primary Outcome(s)

Forced Expiratory Volume in 1 Second (FEV1 slope) [Time Frame: 2 years]

Secondary Outcome(s)

Total Lung Capacity (TLC) [Time Frame: 2 years]

Diffusing Capacity for Carbon Monoxide (DLCO) [Time Frame: 2 years]

Secondary ID(s)

RLDC5713

U01HL131755-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Heart, Lung, and Blood Institute (NHLBI)

The LAM Foundation

National Center for Advancing Translational Sciences (NCATS)