Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Sclerosis

Lymphangioleiomyomatosis

Tuberous Sclerosis

Hamartoma

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Lymphangiomyoma

Neoplasms by Histologic Type

Perivascular Epithelioid Cell Neoplasms

Neoplasms, Connective and Soft Tissue

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Tuberous Sclerosis Complex

Molly S Griffith, BA

Adrienne Victory

David M Ritter, MD, PhD

This study is an observational registry designed to gather information about Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) in pregnant women and their child.

Tuberous sclerosis complex (TSC) is caused by mutations in tuberous sclerosis complex 1 (TSC 1) and tuberous sclerosis complex 2 (TSC 2) leading to overactivation of the mammilian target of rapamycin (mTOR) pathway resulting in multiorgan disease. Specifically, patients are at risk for autism, epilepsy, intellectual disability, renal cysts, tuberous sclerosis associated neuropsychiatric disorder (TAND), lymphangioleiomyomatosis (LAM), and benign tumors throughout the body including subependymal giant cell astrocytomas (SEGAs), renal and liver angiomyolipomas (AMLs), and cardiac rhabdomyomas (rhabdomyomas).

Sporadic LAM occurs mostly in women and many patients with LAM have TSC gene mutations.

The purpose of this study is to gather information to help clinicians develop evidence-based guidance for the care of TSC and LAM patients during pregnancy and to provide screening recommendations for fetal TSC.

Participants will be asked to complete monthly online surveys screening for changes in the pregnancy, maternal health/medication changes, and other care. For infants enrolled after birth, clinical data will be collected and reviewed for up to 5 years of age.

Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)

Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry

Assess number of days participant takes mTOR inhibitor in relation to number of days participant was supposed to take mTOR inhibitor.

Review mTOR inhibitor dosing for each participant.

Monitor side effects of mTOR inhibitor experienced by participant.

Screening for changes in pregnancy, maternal health/medication changes and other care by using a study-developed monthly questionnaire inquiring about pregnancy status, maternal and/or fetal testing, changes to maternal and fetal care clinical providers, addition or removal of medications, changes in medication doses, and addition of new complications to mother and/or fetus using a list of common gestational complications within prior month.

Participant will complete Tuberous Sclerosis Complex associated Neuropsychiatric Disorders (TAND) questionnaire.

Participant will complete the Edinburgh Postnatal Depression Scale (EPDS).

Compare fetal imaging to imaging and clinical data including echocardiograms, electrocardiograms, genetic testing results, magnetic resonance images of the brain and abdomen, ultrasounds.

David M. Ritter

Sponsor/Principal Investigator

Anti-Infective Agents

Antirheumatic Agents

All Drugs and Chemicals

Antineoplastic Agents

Hydroxychloroquine

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Subjects will take Sirolimus at an initial dose of 2mg followed by dose adjustment to keep Sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to Sirolimus subjects will receive Hydroxychloroquine at 200 mg daily for 6 months. Once safety is established at the lower dose ("Sirolimus" and "Hydroxychloroquine" 200 mg), subjects enrolled henceforth will receive Sirolimus and Hydroxychloroquine 400 mg (200 mg twice a day) for 6 months.

This will be a phase I dose escalation study of the combination of "Sirolimus" (2 mg adjusted to keep trough levels between 5-15 ng/ml) and "Hydroxychloroquine" 200 mg taken orally daily.

"Sirolimus" and "Hydroxychloroquine" 200 mg

Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day.

"Sirolimus" and "Hydroxychloroquine" 400 mg

Elizabeth P Henske, MD

Joel Moss, MD, PhD

Specific Aim 1: To investigate whether, in Lymphangioleiomyomatosis (LAM) patients, the combination of sirolimus and hydroxychloroquine is safe and well tolerated

Specific Aim 2: To investigate whether, in LAM patients, 6 months of combination therapy with sirolimus and hydroxychloroquine results in improvement of indicators of disease, and whether the gains are sustained after stopping therapy.

Specific Aim 3: To investigate the potential role of a LAM-specific peripheral blood signature to predict rates of disease progression and determine responsiveness to combination therapy.

This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily. Up to 18 adult women with LAM will be enrolled.

This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily for 6 months. The study is to be conducted at 2 sites. Up to 18 adult women with LAM will be enrolled, and each recruiting site will recruit between 8-12 subjects. The protocol will use the following eligibility criteria.

Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis

Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus

The Primary endpoint of this study was safety. Safety was assessed based on the adverse events and serious adverse events that occurred in these patients when they were on this combination therapy. Percentage of adverse events in each system at a dose was calculated from the total adverse events at that dose. Subjects were closely monitored and adverse events were classified and graded according to the "Common Terminology Criteria for Adverse Events, (CTCAE) Version 4.0".

National Heart, Lung, and Blood Institute (NHLBI)

Brigham and Women's Hospital

Overall Principal Investigator

This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily.

Sirolimus and Hydroxychloroquine 200 mg

Sirolimus and Hydroxychloroquine 400 mg

Subjects will take sirolimus at an initial dose of 2mg followed by dose adjustment to keep sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to sirolimus subjects will receive hydroxychloroquine at 200 mg daily or twice a day for 6 months, depending on time of enrollment into the study, following a standard phase I dose escalation.

sirolimus and hydroxychloroquine: This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily.

Sirolimus and Hydroxychloroquine

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Post-Menopause

Pneumothorax

Angiomyolipoma

Tuberous Sclerois (TSC)- Lymphangioleiomyomatosis (LAM)

Lung Biopsy

Chylothorax

6 minute walk distance (6MWD) (m)

The Saint George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.

St. George's Respiratory Questionnaire (SGRQ)

Log VEGF-D (Veascular Endothelial Growth factor)

FEV1

FEV1 (%)

FVC (L)

FVC (%)

DLCO (ml/min/mmhg)

DLCO (%)

1 subject failed to qualify for the study at the screening visit. Since the subject had signed consent, we considered the participant to be enrolled on the study.

Elizabeth P. Henske, MD

Cardiac Disorders

Eye Disorders

GI Disorders

General Disorders, Administration site condistions

Immune System disorders

Infections and infestations

Injury, poisoning, procedural complications

Investigations

Metabolism and nutrition disorders

Musculoskeletal, connective tissue disorders

Nervous system disorders

Psychiatric disorders

Renal and urinary disorders

Reproductive system and breast disorder

Respiratory, thoracic, mediastinal disorders

Skin and Subcutaneous disorders

Vascular disorders

This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily. Safety of the drug combination was assessed by the occurrence of adverse events in these 3 patients.

Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day. Safety of this dose was assessed by the occurrence of adverse events in these 10 patients.

Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients

Sirolimus and HydroxyChloroquine 400 mg

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Lung Diseases

Everolimus

women over age 18 who have LAM and are currently taking, have previously failed or been intolerant of, or who are considering taking everolimus as part of their clinical care

women over age 18 who have LAM and are currently taking, have previously failed or been intolerant of, or who are considering taking sirolimus as part of their clinical care

Sirolimus treatment will be part of a participant's clinical care and will be managed by their physician.

Everolimus treatment will be part of a participant's clinical care and will be managed by their physician.

Susan McMahan Sellers, BSN, RN

Francis X McCormack, MD

Stephen Ruoss, MD

Gregory Downey, MD

Charles Burger, MD

Sirhari Veeraraghavan, MD

Elizabeth Henske, MD

Mei Lan Han, MD

Adrian Shifren, MD

MaryAnne Morgan, MD

The MIDAS study aims to follow male and female LAM patients who are currently taking, have previously failed or been intolerant of, or may (at some time in the future) take mTOR inhibitors (sirolimus or everolimus) as part of their clinical care. Adult female TSC patients may also enroll, with or without lung cysts.

Lymphangioleiomyomatosis (LAM) is an uncommon disease affecting women. It is associated with cystic lung destruction and progressive respiratory failure. The Multicenter International LAM Efficacy of Sirolimus (MILES) Trial, led by the investigators' research team, demonstrated that mTOR (mammalian target of rapamycin) inhibition with sirolimus was an effective therapy that stabilized decline in FEV1 (forced expiratory volume). However, lung function decline resumed when the drug was stopped at the one year point in MILES, suggesting that therapy is suppressive rather than remission-inducing, and may need to be lifelong. There is therefore a need to understand whether long-term therapy with sirolimus is safe and effective. To accomplish this goal, the investigators will conduct the Multicenter International Durability and Safety of Sirolimus in LAM Trial (MIDAS). This is an observational, real world registry. The investigators propose to enroll 600 LAM patients who are on, have previously failed or been intolerant of or are considering taking sirolimus or everolimus for clinical reasons in a longitudinal observational study. This registry will follow lung function tests and adverse events that are obtained for clinical purposes over periods of at least 2 years. The decision to treat with mTOR inhibitor therapy is made by the clinician and the patient, and will be managed by the participant's clinician. This study will help us to refine treatment for patients with LAM and determine if long term suppressive therapy with sirolimus can prevent progression to later stages of disease. This research will be accomplished as part of the NIH/NCATS Rare Lung Disease Consortium, with data stored and analyzed by the Database Management Coordinating Center (DMCC) at the University of South Florida.

Safety and Durability of Sirolimus for Treatment of LAM

Multicenter International Durability and Safety of Sirolimus in LAM Trial (MIDAS)

Symptoms and adverse events will be recorded

time from enrollment to 10% or greater reduction in FEV1(forced expiratory volume) in months

Evaluate ATAQ-LAM QOL responses over time

Rare Diseases Clinical Research Network

National Institutes of Health (NIH)

The LAM Foundation

University of Cincinnati

Professor

Patients will perform a comprehensive, inpatient pulmonary rehabilitation program for 4 weeks duration

Pulmonary Rehabilitation

Rembert A Koczulla, MD

Data from patients with the orphan disease of lymphangioleiomyomatosis (LAM) which performed a pulmonary Rehabilitation program will be analyzed retrospectively. Data will be taken from the internal data base of the reference Center (Schoen Klinik Berchtesgadener Land, Schoenau, Germany) where These data were collected during clinical routine. Data will be included from the year 2000 until now. A retrospectively matched COPD cohort will be included for comparison.

Benefits of Pulmonary Rehabilitation in Patients With Severe Lymphangioleiomyomatosis (LAM)

Benefits of Pulmonary Rehabilitation in Patients With Severe Lymphangioleiomyomatosis (LAM) - a Retrospective Analysis

the walked distance in meter will be the Primary outcome of the 6 Minute walk test

the physical and mental health component summary score from the Short Form 36 Health Questionnaire will be recorded. Score range from 0 to 100 with lower scores indicating worse impairment

forced expiratory volume in 1 second and inspiratory vital capacity will be provided in Liter and percent predicted

Schön Klinik Berchtesgadener Land

Prof. Dr.

Hematinics

Liver Extracts

Saracatinib

Saracatinib will be given orally at a dose of 125 milligrams once daily for 9 months. Saracatinib is provided as a pink tablet.

Subjects will receive enough tablets for 90 days +/- 14 days at each visit. Subject will have visits every 90 days for drug accountability as well as safety and efficacy testing to include pulmonary function testing, laboratory testing to include liver and kidney profile, urine pregnancy testing at each visit, vital signs, physical examination - any medically significant changes from baseline visit will be recorded, all adverse events will be monitored until resolution.

saracatinib

Tony Eissa, MD

Nicola A Hanania, MD

Daniel Dilling, MD

Joel Moss, MD

This study is being done to determine if there is a potential benefit of saracatinib in LAM subjects. Based on the information of this trial, additional clinical development trials will be needed. The study will also test the tolerability of 125 mg of saracatinib given once daily over a 9 month period.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in tuberous sclerosis complex 1 (TSC1) or TSC2 tumor suppressor genes. TSC is characterized by tumors in a wide range of tissues, seizures, mental retardation, autism, and organ failure. Lymphangioleiomyomatosis (LAM), the major pulmonary manifestation in women with TSC, is a progressive lung disease characterized by infiltration of atypical smooth muscle like cells (TSC-/- LAM cells) and formation of parenchymal cysts. Sporadic LAM can develop in women who do not meet the criteria for the diagnosis of TSC, owing to somatic mutations in the TSC2 gene.

The long term goal of this research is to devise novel therapeutic strategies for patients with LAM. The observed behavior of LAM cells with respect to their infiltrative growth pattern, metastatic potential, and altered cell differentiation is reminiscent of cells undergoing epithelial-mesenchymal transition (EMT). Src kinases are key regulators of cellular proliferation, motility, invasiveness and EMT. Recent results have shown that autophagy promotes degradation of active Src. Thereby, decreased autophagy due to mTOR activation known to occur in LAM cells, may play a significant role in accumulation of active Src in these cells. Src suppresses transcription of E-cadherin by upregulating its transcriptional repressors. The preliminary data reveal an increase in active Src in lung tissues of patients with LAM as well as in cultured TSC2-/- cells. Further, in TSC2-/- cells, E-cadherin is considerably reduced and does not localize to the plasma membrane, as it does in wild-type cells.

The focus of this study is to examine if Src inhibition represents a potential therapeutic strategy in LAM. It is proposed that Src activation in TSC2-/- cells results in the reduction of E-cadherin, loss of cell-cell adhesion and elevation of oncogenic and metastatic potential of these cells. The increased Src activity in TSC2-/- cells is likely caused by inhibition of autophagy associated with hyper-activation of mTOR. Therefore, the use of Src inhibitors may lead to a reduction in tumor growth and prevent dissemination of TSC2-/- cells. In this study, the investigators will evaluate the safety and efficacy of Src inhibition in subjects with LAM.

A number of inhibitors of Src are now in clinical trials in patients with a range of different tumors. Dasatinib, an oral adenosine triphosphate (ATP)-competitive Src inhibitor, is now approved for clinical use in patients with chronic myeloid leukemia or acute lymphoblastic leukemia. However, dasatinib has wider 'off target' inhibitory activity than saracatinib including potent activity against Abl, ephrin receptor kinases, platelet-derived growth factor receptor and c-KIT (type of receptor tyrosine kinase and a type of tumor marker. Also called CD117 and stem cell factor receptor.) In contrast, saracatinib has a \>10-fold preference for Src over Abl kinases and has very little activity against other tyrosine and serine/threonine kinases. Saracatinib has been already characterized in multiple clinical trials in terms of safety and pharmacokinetics.

The investigators have conducted a Phase1b study to test the safety of various doses of Saracatinib in LAM subjects. The purpose of the Phase1b trial was to determine the optimal dose in terms of safety and tolerability in LAM population. Three escalating doses of saracatinib; 50, 125 and 175 mg were studied. Saracatinib was given orally once a day. Overall, subjects tolerated Saracatinib well. The investigators chose the dose of 125 mg to conduct further testing of both safety and efficacy in this Phase 2a trial.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)	NCT06160310	Tuberous Sclero... Lymphangioleiom...		-	Children's Hospital Medical Center, Cincinnati
Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)	NCT06160310	Tuberous Sclero... Lymphangioleiom...		-	Children's Hospital Medical Center, Cincinnati
Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis	NCT01687179	Lymphangioleiom...	"Sirolimus" and... "Sirolimus" and...	18 Years - 85 Years	Brigham and Women's Hospital
Safety and Durability of Sirolimus for Treatment of LAM	NCT02432560	Lymphangioleiom...	Sirolimus Everolimus	18 Years -	University of Cincinnati
Benefits of Pulmonary Rehabilitation in Patients With Severe Lymphangioleiomyomatosis (LAM)	NCT04184193	Lymphangioleiom... LAM Pulmonary Rehab...	Pulmonary Rehab...	18 Years -	Schön Klinik Berchtesgadener Land
Safety and Efficacy of Saracatinib In Subjects With Lymphangioleiomyomatosis	NCT02737202	Pulmonary Lymph...	saracatinib	18 Years - 65 Years	Baylor College of Medicine

Spots Global Cancer Trial Database for lam

Every month we try and update this database with for lam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lam

Every month we try and update this database with for lam cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.