LAM Clinical Trials

Well-conducted clinical trials are the fastest and safest way to find improved treatments and preventions for diseases like LAM. Several LAM trials are underway. Click on the links below to learn more about LAM trials in progress.

The MILES Trial (US)
TESSTAL Study (UK)
TSC Multicenter Clinical Trial (US)

Click here for additional patient information on Clinical Trials

MlLES Trial Interim Results

The Data Safety Monitoring Board (DSMB) recently completed their review of an early interim analysis of study data for the MlLES Trial. The review included study data from the first forty MlLES Trial participants who have completed their first year in the study.

The DSMB recommends that the MlLES Trial continue through August, 2010 until all
actively-enrolled study participants have completed their 12-month study visit.

During this time, the MlLES study staff and participants will remain "blinded" to their treatment group (that is, they will not know who is on placebo and who is on sirolimus).

After August, 2010, the final analysis will be conducted. At that time more information will be available regarding the effectiveness and safety of sirolimus in treating LAM. All study staff and participants will then be "unblinded" to individual participant treatment assignments.

To look at some FAQ on the Miles Trial Interim Results click here.

The MILES Trial

Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus

A randomized controlled study supported by the NIH Rare Lung Diseases Consortium

Principal Investigator: Francis X. McCormack, MD

Trial Coordinators: milestrial@cchmc.org

LAM Foundation Contact: Sally Lamb, (513) 777-6889

Primary Site: Cincinnati Children's Hospital Medical Center/University of Cincinnati. for other site locations click here.

Objectives: The objectives of this study are to assess the efficacy and safety of sirolimus in patients with LAM.

Rationale: Sirolimus blocks signaling through the Akt cell growth and survival pathway that is dysregulated in patients with LAM.

Study Design: The trial will be randomized, double-blind, placebo-controlled. Up to 120 study subjects (60 per arm) will be treated with placebo or sirolimus (2 mg) orally for a period of 12 months, then studied off therapy for 12 months. Pulmonary function, exercise tolerance and quality of life will be measured. There will be an interim analysis when 50 patients reach the one year point. The total duration of the study will be three years. If, at the time of the interim analysis, it is determined by the Data Safety Monitoring Board (DSMB) that sirolimus has a beneficial effect on lung function, then all subjects will receive sirolimus and the study will continue "open label" through the two-year point. The DSMB may interrupt or stop the study at any time if the treatment causes unacceptable side effects or worsens lung function.

Inclusion Criteria:

Age 18 or over
Signed and dated informed consent
Diagnosis of LAM as determined by biopsy; or chest CT scan findings compatible with LAM in the setting of tuberous sclerosis, angiomyolipoma or chylous pleural effusion
Abnormal lung function ( i.e., postbronchodilator FEV1 less than or equal to 70percent of predicted)

Exclusion Criteria:

History of myocardial infarction or stroke related to atherosclerosis
Pregnancy or breast feeding
Inadequate contraception
Significant hematologic or hepatic abnormality
Intercurrent infection at initiation of sirolimus
Recent surgery (involving entry into a body cavity) within two months of initiation of sirolimus
Use of an investigational drug within the last 30 days
Uncontrolled hyperlipidemia
Previous lung transplantation
Inability to attend scheduled clinic visits
Inability to give informed consent
Inability to perform pulmonary function testing
Creatinine >2.5 mg/dl
Chylous ascites sufficient to affect diaphragmatic function
Pleural effusion sufficient to affect pulmonary function
Acute pneumothorax within the past two months
Allergy to sirolimus
Malignancy other than uncomplicated skin cancer in the past two years

Study Visit: Baseline, three weeks, three months, six months, nine months, 12 months, 18 months and 24 months. Travel expenses are funded.

Primary Endpoint: FEV1 response

Secondary Endpoints: Six minute walk, FVC response, lung volumes, diffusing capacity

To learn more about the trial go to http://www.rarediseasesnetwork.org/ and sign the contact registry.
To inquire about travel funding for the trial, email Sally Lamb.

TESSTAL STUDY

A Trial of the Efficacy and Safety of Sirolimus (Rapamycin) therapy for renal angiomyolipomas in patients with Tuberous Sclerosis Complex And Sporadic Lymphangioleiomyomatosis

The study started in October 2005 and is expected to complete in August 2009. All patients have now been enrolled in the study which has now completed recruiting.

Lay summary

This study examines the effect of Rapamycin on the size of renal angiomyolipomas in patients with either tuberous sclerosis or sporadic LAM. All patients receive Rapamycin for two years. Size angiomyolipoma is examined by renal MRI at the start and throughout the study. All patients have tests of their cognitive function and those with sporadic LAM have regular pulmonary function tests. All patients have regular monitoring of blood tests and Rapamycin levels.

Study details

Inherited mutations of the TSC1 or TSC2 gene cause tuberous sclerosis while acquired (somatic) mutations of either gene are associated with sporadic lymphangioleiomyomatosis (LAM). Renal angiomyolipomas are a feature of both disorders. TSC1 and TSC2 regulate signalling through the mammalian target of rapamycin (mTOR) pathway. Inhibition of mTOR may result in a decrease in size of TSC 1/2 associated lesions. We are treating patients with tuberous sclerosis or sporadic LAM with the mTOR inhibitor Rapamycin in a non-randomised, open label pilot study of safety and efficacy. Change in size of renal angiomyolipomas is the primary end point

Primary Outcome Measure:

Size of renal angiomyolipomas assessed by MRI scan over 24 months

Secondary Outcome Measures:

Respiratory function tests (FEV₁, FVC, DLCO)
Cognitive function (memory, executive skills)
Adverse events and safety

Eligibility

Ages Eligible for Study: 18 Years - 65 Years,

Inclusion Criteria:

If female, documentation of negative pregnancy test prior to enrolment.
Participants, including males, must use an effective form of contraception, whilst taking sirolimus and for twelve weeks after stopping the drug
One or more renal angiomyolipomata of at least two centimetres or greater in largest diameter
Adequate renal function :glomerular filtration rate > 40 ml/min
Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria) or sporadic LAM (biopsy-proven or compatible high resolution chest CT scan and respiratory function tests.)
Signed and dated informed consent

Exclusion Criteria:

History of non-compliance or inability to give informed consent
Significant haematological or hepatic abnormality (i.e. transaminase levels > 150 i.u./L serum albumin < 30 g/L, haematocrit< 30%, platelets < 100,000/ mm3, adjusted absolute neutrophil count < 1,500/mm3, total WBC < 3,000/ mm3)
Greater than 1 g proteinuria daily
Multiple bilateral AMLs, where individual lesions cannot be distinguished
Renal haemorrhage within preceding year
In those who have had a renal haemorrhage, known conservatively managed renal aneurysm(s) greater than 10mm
Patients who have had embolisation for AML(s) within the preceding 6 months
Patients who are unable to walk 100 metres on the flat
Continuous requirement for supplemental oxygen
Patients who have had or are being considered for organ transplant
Uncontrolled hyperlipidaemia
Intercurrent infection at initiation of Sirolimus
Surgery within last 2 months
Pregnant or lactating women
Use of an investigational drug within the last 30 days
Change in anti epileptic drug medication within the last 3 months
Likely to need vaccination e.g. for travel during the course of the trial (except for influenza vaccine in patients with LAM)
Current usage of strong inhibitors of CYP3AE ( such as ketoconazole, voriconazole, itraconazole, tilithromycin or clarithromycin) or strong inducers (such as rifampicin or rifabutin)

Location and Contact Information

There are study centres in Cardiff, Nottingham and Brighton UK

Cardiff

Julian Sampson Principal Investigator sampson@cf.ac.uk
Mark Davies Trial Coordinator daviesdm@cf.ac.uk

Nottingham
Simon Johnson simon.johnson@nottingham.ac.uk

Anne Tattersfield anne.tattersfield@nottingham.ac.uk

Brighton

Chris Kingswood chris.kingswood@bsuh.nhs.uk

Zurich

Andreas Serra andreas.serra@usz.ch

ClinicalTrials.gov Identifier: NCT00490789

We are currently open for enrollment at the following sites:

Doctor	Clinical Site	City	Telephone
Dr. Elizabeth Thiele	Mass.General Hospital	Boston, MA	617-726-6540
Dr. Daniel Miles	New York University	New York, NY	212-263-8318
Dr. David Franz	Cincinnati Children's Hosp.	Cincinnati, OH	513-636-4222
Dr. Arthur Sagalowsky	Univ. of Texas, Southwestern	Dallas, TX	214-645-8797
Dr. Francis DiMario	Conn. Children's Med. Ctr.	Hartford, CT	860-545-9460
Dr. Peter Crino	Univ. PA Medical Center	Philadelphia, PA	215-349-5312
Dr. Stephen Ashwal	Loma Linda University	Loma Linda, CA	909-835-1825

SOME ADDITIONAL INFORMATION IS INCLUDED BELOW

If you have any questions about this study, please contact Dr. Sandra Dabora (study organizer) at sdabora@partners.org or 617-355-9004.

YOU CAN FIND GENERAL INFORMATION ABOUT CLINICAL TRIALS AT: http://www.clinicaltrials.gov/
YOU CAN FIND MORE DETAILS ABOUT THIS TRIAL AT: http://clinicaltrials.gov/show/NCT00126672

Sirolimus in Treating Patients With Angiomyolipoma of the Kidney

RATIONALE: Drugs used in chemotherapy, such as sirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well sirolimus works in treating patients with angiomyolipoma of the kidney.

Official Title: Phase II Study of Sirolimus in Patients With Angiomyolipoma of the Kidney Secondary to Tuberous Sclerosis or Lymphangioleiomyomatosis (Further study details as provided by National Cancer Institute (NCI):

Primary Objectives:

Determine the efficacy of sirolimus, in terms of objective response rate, in patients with angiomyolipoma of the kidney secondary to tuberous sclerosis (TSC) or lymphangioleiomyomatosis (LAM).
Determine the toxicity of this drug in these patients.

Secondary Objectives:

Determine changes in other TSC lesions (e.g., tubers, subependymal giant cell astrocytomas, facial angiofibromas, or kidney cysts) in patients with TSC treated with this drug.

Determine changes in pulmonary disease in patients with LAM treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral sirolimus once daily for 12 months in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed at 6 months and 1 year.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

ELIGIBILITY

Ages Eligible for Study: 16 Years - 65 Years, Genders Eligible for Study: Both

CRITERIA

DISEASE CHARACTERISTICS:

Diagnosis of angiomyolipoma of the kidney secondary to tuberous sclerosis (TSC) or lymphangioleiomyomatosis (LAM)
Tumor ≥ 2 cm by MRI
No evidence of severe LAM, defined as either of the following:
Dependent on continuous oxygen

PATIENT CHARACTERISTICS:

Age 16 to 65
Adequate renal and liver function

OTHER:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No unstable seizures, defined as a recent change in seizure pattern or change in antiepileptic drug regimen
No active infection
No significant bleed associated with kidney angiomyolipoma within 30 days
No untreated renal cancer
More than 30 days since prior investigational agents
More than 6 months since prior vascular embolization therapy for treatment of kidney angiomyolipomas
No concurrent chronic use of diltiazem, ketoconazole, or rifampin

No other concurrent investigational agents

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