PQR309 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

Inclusion Criteria: 1. ≥18 years of age. 2. Patient with histologically/cytologically confirmed Primary Central Nervous System Lymphoma (PCNSL) 3. Relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) demonstrated by cranial MRI. 4. Presence of at least one lesion of bi-dimensionally measurable disease on baseline 5. MRI with a contrast-enhancing tumor of at least 1 cm (10 mm) in the longest diameter. 6. Maximum one prior systemic therapy regimen. 7. If receiving corticosteroids, patients must have been on a stable or decreasing dose of corticosteroids and no more than 8 mg dexamethasone (or equivalent) for at least 5 days prior to date of enrollment. 8. Karnofsky Performance Score (KPS) ≥ 70%. 9. More than 4 weeks from any investigational agent. 10. Adequate haematological, liver and renal function 11. Able and willing to swallow and retain oral medication. 12. Female and male patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment. 13. Willing and able to sign the informed consent and to comply with the protocol for the duration of the study. Exclusion Criteria: 1. Central Nervous System (CNS) Lymphoma or chronic immunosuppression-associated central nervous system (CNS) lymphoma. 2. Previous allogeneic hematopoietic stem cell transplant (HSCT transplant). 3. Previous whole brain radiotherapy (WBRT) 4. Other concomitant anti-tumor therapy as determined by the study team. 5. Patients unable to undergo contrast-enhanced MRI. 6. Prior treatment with a phosphoinositide -3 kinase (PI3K) inhibitor, Protein Kinase B Inhibitor is known as AKT inhibitor, or mammalian target of rapamycin (mTOR) inhibitor. 7. Patient taking enzyme-inducing anti-epileptic drug (EIAED) \< 7 days of the first dose of PQR309. 8. Patient is taking a drug with a risk to promote QT prolongation and Torsades de Pointes. 9. Patient is currently using herbal preparations or medications. Patient should stop using herbal medications 7 days prior to the first dose of the study drug. 10. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders. 11. Anxiety ≥ Common Terminology Criteria (CTC) of adverse events (AE) grade 3. 12. Patient has an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, HIV infection, chronic liver disease. chronic renal disease, pancreatitis, chronic pulmonary disease, active cardiac disease or cardiac dysfunction, interstitial lung disease, active autoimmune disease, uncontrolled diabetes, neuropsychiatric or social situations that would limit compliance with the study requirements. 13. Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug. 14. Concomitant treatment with medicinal products that increase the potential hydrogen (pH), reduce acidity of the upper gastrointestinal tract, including, but not limited to, proton-pump inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids. Patients may be enrolled in the study after a washout period sufficient to terminate their effect. 15. Patient has a history of invasive malignancy other than Primary Central Nervous System Lymphoma (PCNSL). Patients are eligible, if they are disease-free for at least 3 years and deemed to be at low risk for recurrence by the investigator. Patients diagnosed with cervical cancer in situ, basal cell or squamous cell carcinoma of the skin and treated within the past 3 years are eligible. 16. Women who are pregnant or breast feeding. 17. Women able to conceive and unwilling to practice an effective method of birth control from screening until 90 days after discontinuing study treatment (women of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of PQR309). 18. Fasting glucose \> 7.0 mmol/L (126 mg/dL). or HbA1c \> 6.4%.