A Study of Nintedanib for LymphAngioleioMyomatosis (LAM)

Inclusion Criteria:

* Written Informed Consent for participating to trial.
* Patient aged ≥ 18 years at visit 1.
* Sporadic or TSC associated LAM, classified as ''definite'' by the European Respiratory Society criteria and /or serum VEGFD level \>/= 800 mg/ml, and evidence of a 10% deterioration in FEV1 and /or loss of 80 ml of FEV1 or more in the last year (post bronchodilator). Also LAM patients with proven side effects and/or toxicities/ contraindications to sirolimus therapy will be eligible for this study.

Exclusion Criteria:

Laboratory parameters have to satisfy entry criteria as shown below:

* Laboratory parameters (screening)

  * AST, ALT \> 1.5 x ULN
  * Bilirubin \> 1.5 x ULN
* Positivity for HIV or Hepatitis.
* Chylous effusions.
* Relapsing pneumothorax.
* Angiomyolipoma \> 5 cm.
* Treatment with mTOR inhibitors in the last month.
* Patient eligible for Lung Transplantation.
* Hormone therapy.
* Patients are excluded if they are post lung transplant or had previously been diagnosed with a pneumothorax, chylous effusion, bleeding angiomyolipoma within the previous 6 months.
* Current smokers.
* Other diseases:

  * Cardiac disease.
  * Myocardial infarction within 6 months of visit 2.
  * Unstable angina within 1 month of visit 2.
* Bleeding Risk:

  * Known genetic predisposition to bleeding.
* Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, heparin, NOA) or high dose antiplatelet therapy2.
* History of haemorrhagic central nervous system (CNS) event within 12 months prior to visit 1.
* History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1.
* International normalised ratio (INR) \> 2 at visit 1.
* Prothrombin time (PT) and partial thromboplastin time (PTT) \> 150% of institutional ULN at visit 1.
* Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery.
* History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1.
* History of end-stage renal disease requiring dialysis.
* Alcohol or drug abuse which in the opinion of the treating physician would interfere with treatment.
* Pts that cannot perform PFT and cannot give informed consent.
* Known hypersensitivity to the trial drug or its components.
* Other disease that may interfere with testing procedures or in the judgement of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial.

General Exclusion Criteria:

* Previous treatment with nintedanib.
* Other investigational therapy (participation in research trial) received within 8 weeks of visit.
* Thoracic, abdominal, gynecological, neurologic surgical procedures planned to occur during trial period.
* Pregnant women or women who are breast feeding or of child bearing potential not using two effective methods of birth control (one barrier and one highly effective non-barrier) for at least 1 month prior to enrolment (and until 3 months after treatment end).
* Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or postmenopausal for at least two years.