|Exclusion Criteria:||1) Treatment with the following therapies within the specified time period: For Dose escalation/MTD confirmation Phase only: Any prior treatment with a PI3K inhibitor. • For Expansion Phase only: Prior PI3K inhibitor within 4 weeks of the start of IPI-145 administration • Tyrosine kinase inhibitor within 7 days of the start of IPI-145 administration. • Any chemotherapy with the exception of hydroxyurea and intrathecal (IT) prophylactic chemotherapy, radiation therapy (other than whole brain irradiation [WBI]), surgery or ablative therapy within 3 weeks of the start of IPI-145 administration. • Investigational therapy within 3 weeks of the start of IPI-145 administration. Investigational agents with a half-life of greater than 3 days, or with a half-life that is unknown, should be discussed with the medical monitor on a case-by-case basis. • Nitrosoureas or mitomycin C within 6 weeks of the start of IPI-145 administration.|
2) Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine following transplant or systemic steroids). For Expansion Phase Cohorts: systemic steroids are allowed at study treatment initiation with the intent to wean to physiologic replacement (< 10 mg prednisone QD) by end of treatment Cycle 1.
3) Patients with overt leptomeningeal leukemia or CNS lymphoma. Patients must be free of CNS disease for a minimum of 2 months. Patients with symptoms of CNS disease must have a negative diagnostic lumbar puncture prior to study enrollment.
4) Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN); direct bilirubin >1.5 x ULN.
5) For Dose escalation/MTD confirmation Phase Only: Inadequate bone marrow function defined by ANC < 750 cells/mm3, platelet count < 75,000 mm3, and a hemoglobin < 8 g/dL without transfusion or cytokine support for > 2 weeks prior to the start of study treatment. Patients who require transfusions or growth factor support are eligible.
6) Inadequate renal function defined by serum creatinine > 1.5 x ULN.
7) For Dose escalation/MTD confirmation Phase Only: Baseline QTcF > 450 ms. NOTE: This criterion does not apply to patients with a left bundle branch block. For Expansion Phase Cohorts: Baseline QTcF > 480 ms. NOTE: This criterion does not apply to patients with a left bundle branch block.
8) Concurrent treatment with any agent known to prolong the QTc interval.
9) Prior surgery affecting drug absorption or any gastrointestinal dysfunction that could alter drug absorption (e.g., gastric bypass surgery, gastrectomy).
10) Patients with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
11) Patients with a history of tuberculosis within the preceding two years.
12) Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation and who meet any of the following criteria: • Have been on a stable dose of anticoagulation for < 1 month • Have had a Grade 2, 3 or 4 hemorrhage in the last 30 days • Are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement) NOTE: Patients who have had a venous thromboembolic event but do not meet any of the above three criteria are eligible for participation.
13) Patients with a history of alcohol abuse, chronic hepatitis, or other chronic liver disease (other than metastatic disease to the liver): NOTE: Chronic hepatitis includes active infection with hepatitis B or C. All patients will be tested for hepatitis C virus antibodies (HCV Ab) and hepatitis B surface antigen (HBsAg) at screening. Patients with a positive result for HBsAg or HCV Ab will be excluded from enrolling in this study.
14) Concurrent administration of medications or foods that are strong or moderate inhibitors or inducers of CYP3A.
15) Presence of active infection within 72 hours of treatment. Patients with ongoing use of prophylactic antibiotics are eligible as long as there is no evidence of active infection and the antibiotic is not included on the list of prohibited medications.
16) Significant co-morbid condition or disease which in the judgment of the Investigator would place the patient at undue risk or interfere with the study. Examples include, but are not limited to cirrhotic liver disease, sepsis, recent significant traumatic injury and other conditions.
17) Known human immunodeficiency virus (HIV) positivity.
18) Pregnant or lactating women.
19) Unable to receive prophylactic treatment for pneumocystis.