| Exclusion Criteria: | 1) Target Disease Exceptions a) Subjects with known or suspected central nervous system (CNS) leukemia or lymphoma. Evaluation of CSF is not required if there are no suggestive signs or symptoms
2) Medical History and Concurrent Diseases a) Evidence of uncontrolled, active infection</= 7 days prior to administration of study medication b) Current or recent (within 3 months of study drug administration) gastrointestinal disease such as chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease. Non-chronic conditions (e.g. infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting study treatment are not exclusionary c) Conditions requiring chronic systemic (not inhaled) glucocorticoid use, such as autoimmune disease or severe asthma d) Active (symptomatic or requiring current medical treatment) graft versus host disease (GVHD)
3) Medical History and Concurrent Diseases (continued): e) Uncontrolled or significant cardiovascular disease including: i) Uncontrolled hypertension despite optimal medical management ii) Congestive heart failure NYHA (New York Heart Association) class 3 or greater within 3 months iii) Left ventricular ejection fraction (LVEF) < 45% as determined by MUGA or quantitative echocardiogram iv) Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction in the past 6 months v) History of congenital long QT syndrome or clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsade de Pointes). Controlled atrial fibrillation is not an exclusion criterion
4) Medical History and Concurrent Diseases (continued): f) History of medically significant thromboembolic events (excluding events associated with venous access devices) or bleeding diathesis (other than bleeding associated with thrombocytopenia) within the past 6 months, such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, pulmonary hemorrhage > 2 teaspoonfuls/24hrs or repeated pulmonary hemorrhage or gastrointestinal hemorrhage requiring transfusion or procedural intervention. Subjects may receive prophylactic platelet transfusions in accordance with institutional policy
5) Medical History and Concurrent Diseases (continued): g) Required anticoagulation therapy with an agent such as warfarin or heparin i) Prophylactic anticoagulation for venous access devices with low-dose heparin or similar (e.g. heparin catheter flush) will be permitted. If warfarin or other vitamin K antagonists are used, the prothrombin time must be </= 1.2 times the institutional upper limit of normal (ULN) or INR < 2 ii) For antiplatelet agents, prophylactic doses are permitted (e.g. aspirin </= 100 mg daily) but must be discussed in advance with the Sponsor/Medical Monitor. Anti-platelet agents should be interrupted during periods of thrombocytopenia < 50,000 cells/mm^3
6) Medical History and Concurrent Diseases (continued): h) Subjects with concomitant second malignancies (except adequately treated non-melanomatous skin cancers or in situ bladder, breast or cervical cancers) are excluded unless a complete remission was achieved and no additional therapy is required or anticipated to be required during the study period i) A serious uncontrolled medical disorder which would impair the ability of the subject to receive protocol therapy j) Inability to be venipunctured and/or tolerate venous access k) Any other sound medical, psychiatric and/or social reason as determined by the Investigator
7) Physical and Laboratory Test Findings: a) Inadequate hepatic function defined as: i) Total bilirubin > 1.5 times the institutional ULN (except known Gilbert's Syndrome); ii) Alanine transaminase (ALT) or aspartate transaminase (AST) > 3 times the institutional ULN b) Uncontrolled (>/= Grade 2) hypertriglyceridemia defined as fasting triglycerides > 300 mg/dL (3.42 mmol/L) c) Inadequate renal function defined as: i) Blood creatinine > 1.5 times the institutional ULN d) Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration, confirmed by repeat: i) QRS > 120 msec, except right bundle branch block ii) QTcF > 450 msec e) Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody 4) Allergies and Adverse Drug Reaction a) History of allergy to BMS-906024-related compounds b) History of Grade 3 or 4 infusion-related reaction to CremophorŽ-containing compounds despite premedication with H1- and H2-blockers
8) Physical and Laboratory Test Findings (continued): 5) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product b) WOCBP using a prohibited contraceptive method (e.g. hormonal methods). Hormonal contraceptives may be used for other indications (e.g. menstrual bleeding) provided it is not the primary method of contraception c) Women who are pregnant or breastfeeding d) Women with a positive pregnancy test on enrollment or prior to investigational product administration
9) Physical and Laboratory Test Findings (continued): 6) Prohibited Treatments and/or Therapies a) Prior exposure to BMS-906024 or other Notch inhibitors b) Use of any herbal supplements within 1 week prior to study drug administration c) Use of medications causing Torsades de Pointes within 1 week or 5 half-lives (whichever is longer) d) Use of strong inhibitors of CYP3A4 within 1 week or 5 half-lives (whichever is longer) or strong inducers of CYP3A4 within 2 weeks or 5 half-lives (whichever is longer)
10) Physical and Laboratory Test Findings (continued): 7) Concomitant Therapies a) Concurrent chemotherapy, hormonal therapy, immunotherapy regimens, or radiation therapy, standard or investigational, with the following exceptions: i) Glucocorticoids may be administered for treatment of infusion reaction and as premedication to prevent further infusion reaction, and for treatment of severe diarrhea ii) Palliative radiation therapy to a limited field (e.g. painful bone metastasis, painful lumps), if it is not the sole site of measurable and/or assessable disease, is allowed any time during study participation with prior approval of the Sponsor/Medical Monitor iii) Other permitted use of concomitant anticancer therapy 8) Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness |