PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) =< 3 x ULN for subjects with Gilbert’s disease or with atazanavir- or indinavir-induced unconjugated hyperbilirubinemia without aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation and must have a total bilirubin less than 3.0 mg/dL, within 2 weeks prior to enrollment
Hepatic: bilirubin <1.5 X Upper Limit of Normal (ULN); alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C): Adequate liver function with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 3 X upper limit of normal and total bilirubin less than 2 mg/dL within 7 days prior to first dose of study agent
ELIGIBILITY CRITERIA - PHASE II (ARM D): Adequate liver function with AST/ALT less than 3 X upper limit of normal and total bilirubin less than 2 mg/dL within 7 days prior to first dose of study agent
Obtained =< 21 days prior to registration: Total Bilirubin =< 1.5 x upper limit of normal (ULN)\r\n* NOTE: For bilirubin elevation 1 to 1.5 x ULN, alanine aminotransferase (ALT) above 1.5 x ULN (upper limit of normal) is not permitted\r\n* NOTE: For bilirubin elevation 1 to 1.5 x ULN, aspartate aminotransferase (AST) above 1.5 x ULN (upper limit of normal) is not permitted
Liver function tests above the following limits at Screening: total bilirubin >1.5 x upper limit of normal (ULN) unless related to Gilbert's syndrome or hemolysis; aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x ULN; for subjects with liver involvement, AST and/or ALT >5 x ULN;
Adequate liver function as demonstrated by: Total bilirubin of < upper limit of normal (ULN), Aspartate transaminase (AST) and alanine aminotransferase (ALT) ?1.5 × ULN, Alkaline phosphatase (ALP) ?2.5x ULN or <5x ULN if bone metastases are present, Normal serum albumin
Meets laboratory criteria for the following parameters: ANC, platelets, hemoglobin, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, BUN and creatinine.
Clinically-significant inadequate hematological, hepatic and renal function, defined as: Neutrophil count < 1.5 x 10 9/L and platelet count < 100 x 10^9/L; bilirubin > 1.5 x upper limit of normal (ULN); aspartate transaminase (AST) and/or alanine aminotransferase (ALT) > 2.5 x ULN or > 5 x ULN if patient has documented liver metastases; and serum creatinine > 1.5 x ULN
Hepatic status: Serum total bilirubin ? 1 x upper limit of normal (ULN; in the case of known Gilbert's syndrome, a higher serum total bilirubin [< 1.5 x ULN] is allowed), aspartate aminotransferase and alanine aminotransferase ? 1.5 x ULN, and alkaline phosphatase ? 1.5 x ULN;
Adequate hepatic function, with total bilirubin ?1.5 x upper limit of normal (ULN) (except for Gilbert Syndrome: total bilirubin < 3.0 x ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?3.0 x ULN.
Hepatic: Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5.0 x ULN for age.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal (ULN) for patients receiving MAC or ALT and AST =< 10 x ULN for patients receiving RIC, RIC-MMF, or IOC; patients who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC, RIC-MMF or IOC arms if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially reversible with bone marrow transplant
ALT (alanine aminotransferase; SGPT), AST (aspartate aminotransferase; SGPT), alkaline phosphatase (ALP) >2.5 upper limit of normal (ULN), unless attributed to GVHD.
Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN.
Adequate bone marrow and major organ function to undergo a PBSC transplant determined within 30-60 days prior to enrollment using standard phase 1 criteria for organ function defined as:\r\n* Absolute neutrophil count (ANC) >= 1.5 x 10^9 cells/L\r\n* Platelets >= 75 x 10^9/L\r\n* Hemoglobin >= 8 g/dL\r\n* Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal (ULN) (=< 5 x ULN, if documented liver metastases are present)\r\n* Total bilirubin =< 2 x ULN (except patients with documented Gilbert’s syndrome)\r\n* Creatinine < 2 mg/dl (or a glomerular filtration rate > 60)\r\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Severely impaired renal or hepatic function (eg, serum creatinine level > 2 mg/dL [176.8 ?mol/L], blood urea nitrogen level >50 mg/dL [17.9 mmol/L], serum aspartate aminotransferase [AST] level >3 times the upper limit of normal [ULN], or serum alanine aminotransferase [ALT] level > 3 times ULN).
Adequate hepatic function as evidenced by: serum total bilirubin ?1.5 × ULN unless considered due to Gilbert's disease, a gene mutation in UGT1A1 (only for patients who will be receiving AG-221), or leukemic involvement following approval by the study Sponsor; aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ?3.0 × ULN, unless considered due to leukemic involvement following approval by the study Sponsor
Normal organ and marrow function: Leukocytes ? 3000/?L, Absolute neutrophil count ? 1500/?L, Platelets ? 100,000/?L, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ? 2.0 x ULN, AST(SGOT)/ALT (SGPT) ? 1.5 x institutional ULN, creatinine < 1.5 x institutional ULN
Adequate renal and liver function as indicated by: i. Creatinine ? 1.5 x upper-normal limit (ULN) ii. Total bilirubin ? 1.5 x upper-normal limit (ULN) iii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 x ULN iv. Alkaline phosphatase ? 2.5 x ULN
Clinically significant kidney (e.g. glomerular filtration rate [GFR] =< 45ml/minute or creatinine of >= 2 mg/dl) or liver dysfunction (e.g. aspartate aminotransferase [AST]/alanine aminotransferase (ALT) and/or bilirubin >= 2 times upper limit of normal [ULN]) at the time of enrollment that may prevent from safely using chemotherapy; such patients may be allowed to receive low-intensity chemotherapy; patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded; discussion with the principal investigator is encouraged if further clarification is required
Liver function tests meeting one of the following criteria:\r\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) with alkaline phosphatase < 2.5 x ULN OR\r\n* AST and ALT < 1.5 x ULN, with alkaline phosphatase > 2.5 x ULN
have adequate hepatic function, defined as having a serum total bilirubin concentration ?1.5mg/d, or ?2 x the upper limit of normal (ULN) if associated with hepatobiliary metastases or Gilbert syndrome, and having serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations ?2.5 × ULN, or ?5 x ULN for patients with known hepatic metastases;
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN and total bilirubin < 2.0 mg/dL unless due to malignancy or Gilbert’s syndrome in the opinion of the PI or designee
Have serum aspartate aminotransferase (AST) >5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) >5 times ULN at screening, or total bilirubin >=3.0 x ULN at screening (except for documented Gilbert's syndrome), as analyzed by local or central lab.
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x the institutional upper limit of normal (unless demonstrated Hodgkin lymphoma involvement of the liver); estimated creatinine clearance >= 30 ml/min (Cockcroft-Gault) and/or 24 urine analysis as needed
Bilirubin =< 1.5 mg/dl (unless Gilbert's syndrome), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 200 IU/ml for adults; conjugated (direct) bilirubin < 2 x upper limit of normal
Liver function (total bilirubin <2mg/dL and aspartate aminotransferase and/or alanine aminotransferase <3 × upper limit of normal (ULN) or <5 × ULN if related to leukemic involvement)
Liver function (total bilirubin <2mg/dL and aspartate aminotransferase and/or alanine aminotransferase <3 × upper limit of normal (ULN) or <5 × ULN if related to leukemic involvement)
Adequate organ function as indicated by the following laboratory values. All laboratory tests must be obtained within 7 days prior to the first dose of ARQ 751: a. Hematological i. Absolute neutrophil count (ANC) ? 1.5 x 109/L ii. Platelet count (Plt) ? 100 x 109/L iii. Hemoglobin (Hb) ? 9 g/dL iv. International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or ? 3 for subjects receiving anticoagulant therapy such as Coumadin or heparin b. Renal i. Serum creatinine ? 1.5 x ULN or calculated creatinine clearance ? 60 mL/min/1.73 m2 for subjects with serum creatinine levels > 1.5 x institutional ULN c. Hepatic i. Total bilirubin ? 1.5 x ULN ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 3 x ULN or ? 5 x ULN for subjects with known liver metastases d. Metabolic i. Glycated hemoglobin (HbA1c) ? 8%
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (unless demonstrated Hodgkin lymphoma involvement of the liver); estimated creatinine clearance >= 30 ml/min (Cockcroft-Gault) and/or 24 urine analysis as needed
Adequate organ function =< 21 days prior to registration:\r\n* Aspartate transaminase (AST) level =< 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) =< 3 x upper limit of normal (ULN)\r\n* Total bilirubin level of =< 1.5 x ULN\r\n* Creatinine level =< 1.2 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above or below the institutional normal\r\n* Hemoglobin (Hgb) >= 9 g/dl without transfusion or epoetin dependency (=< 7 days prior to assessment)\r\n* Absolute neutrophil count >= 1.5 x 10^9/L\r\n* Platelets >= 100 x 10^9/L\r\n* Albumin >= 2.5 g/dl
Patient must meet the following laboratory values at the screening visit: Absolute Neutrophil Count ?1.5 x 109/L. Platelets ?75 x 109/L. Hemoglobin (Hgb) ?9 g/dL. Serum creatinine <1.5 mg/dL. Total bilirubin ?1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Aspartate transaminase (AST) ? 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ?5.0 x ULN. Alanine transaminase (ALT) ? 3.0 x ULN, except for patients with liver metastasis or tumor infiltration, who may only be included if ALT ?5.0 x ULN. Prothrombin time (PT)/International normalized ratio (INR) and Partial thromboplastin time (PTT) ?1.5xULN. Note: patients receiving therapeutic anticoagulation agents prior screening are permitted. Albumin 2.5 g/dL.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × ULN (>= 5 × ULN for patients with concurrent liver metastasis); OR impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices; OR acute viral or active autoimmune, alcoholic, or other types of hepatitis
Hepatic: Serum/plasma total bilirubin ?1.5 x upper limit of normal (ULN) with the exception of <2.9 mg/dL for patients with Gilbert's disease, ALT (SGPT) and AST (SGOT) ?2.5 x ULN.
Laboratory values: Screening serum creatinine >1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) >3×ULN or >5×ULN if liver metastases are present, total bilirubin >2×ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <100,000/mm3, hemoglobin <9 g/dL, albumin <2 gm/dL.
Adequate hepatic function as defined by the following criteria:\r\n* Total serum bilirubin =< 1.5 x upper normal limit (ULN), unless due to Gilbert’s syndrome\r\n* Alanine aminotransferase (ALT) =< 2.5 x ULN\r\n* Aspartate aminotransferase (AST) =< 2.5 x ULN
Patients must have adequate hepatic function as evidenced by total serum bilirubin ? 1.5 x the upper limit of normal (ULN) and a prothrombin time (PT) within 2 seconds of the upper normal limit. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) must be ? 2.5 x ULN.
Severe major organ toxicity; renal, cardiac, hepatic, pulmonary, gastrointestinal and neurologic toxicity should all be grade 1 or less (per National Cancer Institute [NCI] Common Toxicity Criteria [CTC] version 3 criteria) with the following exceptions:\r\n* Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase should be =< 5 x upper limit of normal (ULN)\r\n* Serum bilirubin =< 3 x ULN and nausea and vomiting should be =< grade 2\r\n* Patients with myelosuppression are not excluded if absolute neutrophil count (ANC) >= 500/uL
Patients with organ dysfunction will not be excluded from the study; for patients with evidence of organ dysfunction (creatinine >= 1.5, cardiac ejection fraction =< 50%, total bilirubin >=2 and aspartate aminotransferase [AST]/alanine aminotransferase [ALT] >= 3 times upper limit of normal [ULN]), dose adjustments/omissions will be made
Adequate liver function (total bilirubin ?1.5 X ULN (or ?3 X ULN in patients with documented Gilbert's syndrome or for patients with hyperbilirubinemia considered due to myeloid disease), alanine aminotransferase [ALT] and aspartate aminotransferase [AST] ?3 X ULN (or ?5 X ULN for patients with liver involvement of their myeloid disease)
Adequate baseline laboratory data: hemoglobin >9 g/dL, absolute neutrophil count (ANC) ?1,000/µL, CD4+ T-cells ?200/µL, platelets ?50,000/µL, bilirubin ?1.5 X upper limit of normal (ULN) or ?3 X ULN for patients with Gilbert's disease, serum creatinine ?1.5 X ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ?3 X ULN.
Have adequate organ function, confirmed by the following laboratory values obtained ? 3 days prior to the first treatment: absolute neutrophil count ? 1.5 × 10^9/L; hemoglobin ? 9 g/dL; platelets ? 100 × 10^9/L; aspartate transaminase and alanine transaminase ? 2.5 × upper limit of normal (ULN); serum total bilirubin ? 2.0 × ULN; serum creatinine ? 1.5 × ULN, or estimated or measured creatinine clearance ? 60 mL/min; prothrombin time, activated partial thromboplastin time ? 1.5 × ULN if not on anticoagulation therapy
Patients with serum aspartate aminotransferase, alanine aminotransferase > 2.5 X the upper limit of normal (ULN) and bilirubin >1.5 ULN
Laboratory values: Screening serum creatinine > upper limits of normal (ULN); total bilirubin > ULN: alanine aminotransferase (ALT) and AST >/= 2.5 ULN or >/= 5.0 x ULN if liver metastases are present; absolute neutrophil count < 1,500/mm3, platelet concentration < 100,00/mm3, hematocrit level < 27% for females or < 30% for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) > 1.5 x ULN unless on therapeutic doses of warfarin.
Adequate hepatocellular function: aspartate aminotransferase (AST) and alanine transaminase (ALT) ? 3x upper limit of normal within institutional limits; bilirubin ? 1.5 mg/dl
Hepatic function: total bilirubin ? 1.5 x ULN (Common Terminology Criteria for AEs [CTCAE] v4.0 grade 1) except patients with Gilbert's disease (up to 5.0 mg/dL). Aspartate aminotransferase (AST) and alkaline phosphatase ? 2.5 x ULN.
Subjects with adequate organ system functions as defined follows: Absolute neutrophil count (ANC) >=1.0 X 10^9/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 10^9/L; Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); Alanine aminotransferase (ALT) <=2.5X ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 meter square (mL/min/m^2); Spot urine (albumin/creatinine ratios [spot urine]) < 500 milligram per gram (mg/g) (56 mg per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) >= 45 percent.
109 Laboratory parameters (completed within 14 days prior to enrollment): Hematology: Absolute neutrophil count (ANC) ? 1.0 x 10^9/L, Platelets ? 75 x 10^9/L. Chemistry: Creatinine clearance ? 50 mL/min (calculated using Cockcroft Gault equation). Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of normal (ULN), Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 3 times the upper limit of normal (x ULN); patients with values > 3 x ULN and < 5 x ULN are eligible if the value is acute and directly related to the infectious process being treated
Must have adequate organ function as defined by the following values: white blood cells >3 x 10^9/liter(L); absolute neutrophil count (ANC) >= 1.5 x 10^9/L; hemoglobin >= 9 grams per decilitre (g/dL) subjects that required transfusion or growth factor need to demonstrate stable hemoglobin for 7 days of 9 g/dL; platelets >=100 x 10^9/L; prothrombin time (PT)/International normalized ration (INR) and partial thromboplastin time (PTT) <= 1.5 x upper limit of normal (ULN); albumin >=2.5 g/dL; total bilirubin <=1.5 x ULN; aspartate transaminase (AST) <=2.5 x ULN; alanine transaminase (ALT) <=2.5 x ULN OR <5 x ULN; creatinine <=1.5 x ULN is acceptable for subjects with documented liver metastases/tumor infiltration; creatinine clearance >= 50 mL/min; ejection fraction>= lower limit of normal (LLN) by echocardiogram or multigated acquisition (MUGA) and minimum of 50% left ventricular ejection fraction (LVEF); testosterone <=50 nanograms per deciliter (ng/dL)
Subject has a total bilirubin ? 1.5 x upper limit of normal (ULN), albumin ? 2.5 g/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 x ULN
Adequate bone marrow function (absolute neutrophil count > 1,500/mm3 and platelet count of > 100,000/mm3), adequate liver function [ALT and AST <3 x upper limit normal (ULN), alkaline phosphatase <2 x ULN, and total bilirubin <1.5 mg/dL], & adequate renal function (BUN and creatinine <1.5 x ULN)
Patients with severe hepatic disease (direct bilirubin greater than 3 mg/dl or aspartate aminotransferase [AST] greater than 500 IU/L)
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal; NOTE: adult values will be used for calculating hepatic toxicity and determining eligibility, as is standard on POB phase I trials
Patient with severe hepatic disease (direct bilirubin greater than 3 mg/dl or aspartate aminotransferase [AST] greater than 500 IU/L)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x institutional ULN; note: patients who have both bilirubin > ULN and AST/ALT > ULN are not eligible (unless they have Gilbert's syndrome and elevations of indirect bilirubin)
Subject has adequate liver function, which is defined as: • Total bilirubin is ? 2 mg/dL unless the increase in bilirubin is attributable to Gilbert's Syndrome • AST is ? 3.0 x upper normal limit (ULN) for age. For the purpose of this study, the ULN for AST is 50 U/L. • ALT is ? 3.0 x upper normal limit (ULN) for age. For the purpose of this study, the ULN for ALT is 45 U/L.
Subjects must have adequate hepatic function as evidenced by: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ?3.0 × ULN, unless considered due to leukemic disease and serum total bilirubin ?1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic disease
Patient must have adequate hepatic function as evidenced by: Serum total bilirubin ?1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement; Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ?2.5 × ULN. For patients with bone metastases and/or suspected disease-related liver or biliary involvement, AST, ALT and ALP must be ?5 × ULN
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x ULN, total serum bilirubin > 1.5 x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ?3.0 mg/dL)
Inadequate organ function immediate prior to randomization including: Hemoglobin <10g/dL (100g/L); ANC < 2000/mm³ (< 2.0 x 109/L); Platelets <100,000/mm³ (< 100 x 109/L); AST or ALT >1.5 x upper limit of normal (ULN); alkaline phosphatase > 2.5 x ULN, total serum bilirubin > 1.25 x ULN; serum creatinine >1.25 x ULN or estimated creatinine clearance < 60 mL/min as calculated using the method standard for the institution; severe and relevant co-morbidity that would interact with the participation in the study
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x ULN, total serum bilirubin > 1.5 x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ? 3.0 mg/dL).
Subject has total bilirubin (TBL) ? 1.5 x the upper limit of normal (ULN) (except subjects with documented Gilbert's disease), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ? 2.5 x the ULN .
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x Upper Limit of Normal (ULN), total serum bilirubin > 1.5 x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ?3.0 mg/dL)
Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ? 2.5 x upper limit of normal (ULN), total bilirubin ? 1.5 x ULN, creatinine ? 2.0 x ULN.
Hepatic: Aspartate aminotransferase/Alanine aminotransferase <3X upper limit of normal (ULN); Total bilirubin <2X ULN (unless Gilbert's Disease or if liver involvement with lymphoma)
Screening chemistry values of the following: alanine aminotransferase (ALT) and aspartate transaminase (AST) ? 3.0 × upper limit of the normal reference range (ULN), total bilirubin ? 2 × ULN, creatinine ? 1.5 × ULN, fasting blood glucose < 140 mg/dL, hemoglobin A1C ? ULN, albumin ? 2.8 g/dL.
Hepatic function: serum albumin >3.0 g/dL; aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <3x the upper limits of normal (ULN); alkaline phosphatase <2x the ULN
Total bilirubin =< 1.5 x upper limit of normal (ULN); patients with known history of Gilbert syndrome and total bilirubin < 2 x ULN and normal aspartate aminotransferase (AST)/alanine aminotransferase (ALT) are eligible, obtained =< 7 days prior to registration
Hepatic: total bilirubin ? 2.5 mg/dL, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) < 5 x upper limit of (ULN) (unless disease related)
Adequate bone marrow, hepatic, renal and coagulation function as defined by the following: Absolute neutrophil count ?1.5 x 10^9/L, Hemoglobin ?9.0 g/dL (90 g/L), Platelets ?100 x 10^9/L, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?2.5 x upper limit of normal (ULN) (if no hepatic metastases). If hepatic tumor involvement, AST and ALT ?5 x ULN, Bilirubin ?1.5 x ULN, Prothrombin time (PT) / international normalized ratio (INR) ?1.5 x ULN, Calculated creatinine clearance >50 mL/min using the Cockcroft and Gault equation
Absolute neutrophil count (ANC) >=1.5 X 10^9/liter (L), Hemoglobin >=9 grams (g)/deciliter (dL) (subjects that required transfusion or growth factor need to demonstrate stable hemoglobin for 7 days of 9 g/dL), Platelets >=100 X 10^9/L, prothrombin time (PT)/ international normalized ratio (INR) and partial thromboplastin time (PTT) - <=1.5 X upper limit of normal (ULN); Hepatic - Albumin >=2.5 g/dL, Total bilirubin <=1.5 X ULN (isolated bilirubin >1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin <35% or subject has a diagnosis of Gilbert's syndrome), Alanine aminotransferase (ALT) <=2.5 x ULN OR <5 x ULN is acceptable for subjects with documented liver metastases/tumor infiltration; Renal - Creatinine <=1.5 X ULN OR Creatinine clearance [either directly measured or calculated by Cockcroft-Gault formula] >=40 milliliter (mL)/minute (min); Cardiac - Ejection fraction >=50% by echocardiogram or multigated acquisition scan (MUGA), Troponin (T) <=ULN, Potassium >=Lower limit of normal (LLN) and <=ULN, Magnesium >=LLN
Hepatic: Serum total bilirubin <=1.5 x upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if their total bilirubin is <= 3.0 mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <= 2.5 x ULN. If the patient has known liver metastases, an ALT and/or AST <= 5 x ULN are allowed.
Has adequate hepatic function defined as total bilirubin ?1.5 mg/dL, unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin or ? 2 ULN. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 × upper limit of normal (ULN) or ? 5 x ULN for subjects with known hepatic metastases.
Major Inclusion Criteria:\n\n          1. Signed written informed consent must be obtained and documented according to the\n             International Conference on Harmonisation (ICH) and be in accordance with local\n             regulatory requirements\n\n          2. A histologically confirmed hematologic malignancy that is advanced, relapsed, or\n             refractory to standard, currently available anti-cancer treatment options\n\n          3. ? 18 years of age\n\n          4. Eastern Cooperative Oncology Group (ECOG) performance status of ? 1 at dose escalation\n             phase and of ? 2 at dose expansion phase\n\n          5. Male or female patients of child-producing potential must agree to use contraception\n             or avoidance of pregnancy measures during the study and for 30 days after their last\n             dose\n\n          6. Females of childbearing potential must have a negative serum pregnancy test\n\n          7. Aspartate transaminase (AST) ? 2.5 x upper limit of normal (ULN) and alanine\n             transaminase (ALT) ? 2.5 × upper limit of normal (ULN). Patients whose disease\n             involves the liver and who have laboratory values of AST ? 3.5 ULN, AST ? 3.5 ULN, and\n             albumin ? 35g/L may be enrolled if agreed upon by the Principal Investigator and\n             Medical Monitor for the Sponsor\n\n          8. Total bilirubin < 1.5 x ULN, except for cases in which elevation of total bilirubin is\n             due to elevated levels of unconjugated bilirubin consistent with a diagnosis of\n             Gilbert's Syndrome\n\n          9. Life expectancy ? 3 months
Adequate bone marrow, liver, and renal function defined as: 1) Absolute neutrophil count (ANC) greater than equal to (>=) 1.5* 10^9cells/litre (L); 2) Platelets >=75 x 109cells/L without transfusion support within 7 days prior to test; 3) Hemoglobin >= 8 gram/deciliter (g/dL) without transfusion support within 7 days prior to test 4) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than equal to (<=) 2.5 * upper limit of normal (ULN) 5) Total bilirubin less than (<) 2 milligram/deciliter (mg/dL) 6) Creatinine determined by serum creatinine levels <=1.5 * ULN or a calculated creatinine clearance of >= 50 mL/min/1.73 m^2
Inadequate liver function: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3 liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >5× upper limit of normal [ULN] for >2 weeks; bilirubin >3× ULN) unless due to underlying disease
The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: total bilirubin must be less than or equal to upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and alkaline phosphatase must be must be less than or equal to 1.5 x ULN for the lab; and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than or equal to 1.5 x ULN for the lab.
Demonstrate adequate organ function as defined below, all screening labs should be performed within 28 days of treatment initiation\r\n* Absolute neutrophil count (ANC) >= 1,000/mcL\r\n* Platelets >= 75,000/mcL\r\n* Hemoglobin >= 9 g/dL\r\n* Serum creatinine =< 2 mg/dl OR creatinine clearance (if creatinine [Cr] > 2 mg/dL) >= 60 mL/min; creatinine clearance should be calculated per institutional standard\r\n* Serum total bilirubin =< 1.5 X upper limit of normal (ULN)\r\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN\r\n* International normalized ratio (INR) =< 1.5 X ULN; activated partial thromboplastin time (aPTT) >= 1.5 X ULN; if on anticoagulant therapy (prothrombin time [PT] or PTT should be therapeutic)
Adequate organ function as determined by: i. Absolute neutrophil count ? 1.5 x 109/L (1,500/mm3) ii.Platelet count ? 100 x 109/L (100,000/mm3) iii.Hemoglobin ? 9.0 g/dL within first 2 weeks prior to first dose of investigational product iv.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/min v.Total bilirubin ? 1.5× ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ? 3× ULN vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ? 2.5× ULN vii.Serum Electrolytes within normal limits
Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN unless disease related.
Total bilirubin level ?1.5 times institutional upper limit of normal (ULN), alanine aminotransferase or aspartate aminotransferase ?2 x ULN
Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN unless disease related.
Subject's total bilirubin is ? 1.5 x upper limit of normal (ULN) (except for subjects with documented Gilbert's disease) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is ? 2.5x upper limit of normal (ULN) at Screening.
The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: Total bilirubin must be less than or equal to 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and ALT must be less than or equal to 2.5 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis;
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) ?3.0 × ULN (Upper limit of normal), unless considered due to leukemic organ involvement.
Acceptable hematology and serum biochemistry screening values: White Blood Cell Count (WBC) >= 1500/mm3; Absolute Neutrophil Count (ANC) >= 1,000/mm3; Platelet (PLT) count >= 75,000/mm3; Hemoglobin (HGB) >= 8 g/dl; Total bilirubin level <= 1.5 x institutional upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN; Creatinine <= 1.5 x ULN; Albumin > 25 g/L
Patients must have WBC >/= 3.5 x 10^9/L, ANC >/= 1.5 x 10^9/L, platelets >/= 100 x 10^9/L, Hb >/= 9.0 g/dL); total bilirubin </= 1.5 x ULN, AST and ALT </= 1.5 x the upper limit of normal; serum potassium of >/= 3.5 mEq/L, serum albumin of >/= 3.0 g/dL, serum creatinine </= 1.5 x ULN
Hepatic: Serum total bilirubin ?1.5 x upper limit of normal (ULN) with the exception of <2.9 mg/dL for patients with Gilbert's disease, alanine aminotransferase (ALT/SGPT) and aspartate aminotransferase (AST/SGOT) ?2.5 x ULN.
Patients must have the following clinical laboratory values unless considered due to leukemic organ involvement: 1. Serum creatinine </= 2.0 mg/dl. 2. Total bilirubin </= 1.5x the upper limit of normal unless considered due to Gilbert's syndrome. 3. Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) </= 3x the upper limit of normal.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?3 × the upper limit of normal (ULN) and total bilirubin ?1.5 × ULN. If the total bilirubin is elevated between 1.5 x and 3 x ULN, patients with a direct bilirubin ? 1.5 X ULN are eligible during the Phase II portion.
Adequate liver function as evidenced by bilirubin less than 1.5 times the upper limits of normal (ULN) and alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than 3 x ULN.
Aspartate aminotransferase and alanine aminotransferase values 3.0 x ULN (or 5x ULN in the case of patients with MF accompanied by hepatic extramedullary hematopoiesis, as manifested by any degree of hepatomegaly).
Subjects must have adequate liver function assessed by: total bilirubin <= 1.0 x upper limit of normal (ULN), aspartate aminotransferase (ALT) <= 3.0 x ULN (CTCAE Grade <=1) or, if receiving BAY1143269 in combination with IV docetaxel, AST and ALT <=1.5 x ULN if concomitant with alkaline phosphatase increase >2.5 x ULN
Hepatic function: Total bilirubin < 1.5 × upper limit of normal (ULN) (except in the case of subjects with known Gilbert's disease: < 5 × ULN) and transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) < 3 × ULN based on age- and institution specific laboratory-specific normal ranges
Serum total Bilirubin ? 1.5 x ULN (upper limit of normal) or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ? 2.5 x ULN
Adequate baseline organ function defined by the criteria below: total bilirubin =< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect [haemolytic] bilirubin in the absence of alanine aminotransferase [ALT] abnormality); ALT =< 2.5xULN; creatinine =< 2.5xULN
Adequate bone marrow function [absolute neutrophil count (ANC) > 1,500/mm3 & platelet count of > 100,000/mm3], adequate liver function [alanine aminotransferase (ALT) & aspartate aminotransferase (AST) <3 x upper limit normal (ULN), alkaline phosphatase <2 x ULN, & total bilirubin <1.5 mg/dL], & adequate renal function (BUN & creatinine <1.5 x ULN)
Elevated serum aspartate aminotransferase, alanine aminotransferase, or bilirubin (unless there is medical justification for bilirubin elevation, and aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase are normal)
Bilirubin =< 1.5 mg/dL AND alkaline phosphatase =< 3 x the upper limit of normal (ULN) for the reference lab (=< 5x the ULN for patients with known hepatic metastases and no limit for patients with known bone metastases) AND aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3x the ULN ( =< 5x the ULN for patients with known hepatic metastases)
Liver dysfunction: aspartate transaminase, alanine aminotransferase increase ?2-fold above the upper-limit of local lab normal ranges.
Have adequate marrow and organ function as defined in Table 2. Table 2 Laboratory Values SYSTEM LABORATORY VALUES Hematologic ANC ?1.5 x 109/L Hemoglobin ?9 g/dL (after transfusion if needed) Platelets ?100 x 109/L Hepatic Albumin ?2.5 g/dL Serum bilirubin ?1.5 x ULN unless due to Gilbert's syndrome AST and ALT ?3 x ULN Renal Calculated creatinine clearance* ? 40 mL/min Serum Creatinine ?1.5 mg/dL or 132.6?mol/L *Calculated by the Cockcroft-Gault Equation (Refer to protocol for details) Abbreviations: ANC, absolute neutrophil count; ULN, upper limit of normal; AST, aspartate aminotransferase; ALT, alanine aminotransferase
Participants with normal major organ functions as defined by hemoglobin (HgB) >= 8.5 gram/decilitre (dL), absolute neutrophil count (ANC) >= 1000/microliter (mcL), platelet >= 60,000/micL, aspartate aminotransferase/alanine transaminase (AST/ALT) <= 3 x Upper Limit of Normal (ULN), total Bilirubin <= 2 x ULN, creatinine <= 2 x ULN.
Participants with normal hepatic function: Total bilirubin and alanine aminotransferase (ALT) must be ? upper limit of the normal range (ULN).
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) <=2.5*ULN • For participants to be treated with MLN4924 + docetaxel in Part B, AST and ALT must be <=1.5*ULN, and total bilirubin should be within the normal range.
Adequate baseline organ function defined as: absolute neutrophil count >= 1.2 x 10^9/Liter (L); hemoglobin>=9 gram per deciliter (g/dL); platelets >= 75 x 10^9/L; prothrombin time /international normalized ratio and partial thromboplastin time =<1.3 x ULN; serum bilirubin=<1.5 times upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase =<2.5 times ULN; serum creatinine=<1.5 mg/dL or calculate creatinine clearance >= 50 milliliter per minute; Left ventricular ejection fraction>= lower limit of normal by echocardiography.
Laboratory values: Screening serum creatinine >1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) >3×ULN or >5×ULN if liver metastases are present, total bilirubin >2×ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <100,000/mm3, hemoglobin <9g/dL.
Adequate hepatic parameters as defined by total bilirubin ? 1.5 x upper limit of normal (ULN) and aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ? 3 x ULN
Total bilirubin level ?1.5 times institutional upper limit of normal (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ?2.0 x ULN except in subjects with known hepatic metastasis, where AST or ALT can be ?5.0 x ULN.
Have adequate baseline organ function defined by the following criteria: Total bilirubin <=1.5 x upper limit of normal (ULN) except for Gilbert's syndrome, or other conditions that are not indicative of inadequate liver function (i.e. elevation of indirect bilirubin (haemolytic) in the absence of alanine aminotransferase [ALT] abnormality). ALT <=3 x ULN. Serum Creatinine <=2.5 x ULN.
Must have adequate organ function as defined by the following baseline values: Absolute neutrophil count >=1.5 x 10^9/Liter, Hemoglobin >=9 gram (g)/decilitre(dL), Platelets >=100 x 10^9/L, Partial thromboplastin time (PTT) <=1.25 x upper limit of normal (ULN), Albumin >=2.5 g/dL, Serum total bilirubin <=1.25 times ULN (for Arm B: <=ULN ), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <=2.5 times ULN (for Arm B: <=1.5 times ULN), Serum Creatinine <=1.5 x ULN, Or Measured or Calculated Creatinine Clearance >=45 mL/min (Arm A or B), >=65 mL/min (Arm C), Left ventricular ejection fraction >=50% by ECHO.
Adequate baseline organ function as defined by: absolute neutrophil count (ANC) >= 1.2 × 109/L; Hemoglobin >= 9 g/dL; Platelet count >= 100 x 109/L; prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) <= 1.5 x upper limit of normal (ULN); Albumin >= 2.5 g/dL; Total bilirubin <= 1.5 x ULN; aspartate aminotransferase (AST) and alanine transaminase (ALT) <= 2.0 x ULN; Creatinine <=1.5 mg/mL; Left Ventricular Ejection fraction (LVEF) >= lower limit of normal (LLN) by ECHO
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBILI) each < 3 x the upper limit of normal (ULN); however, ALT, AST, and TBILI each ? 5 x ULN is acceptable if the elevation is considered by the investigator to be due to PTLD involvement of the liver
Elevated liver function tests (LFTs): Serum bilirubin >upper limit of normal (ULN), alanine (ALT) or aspartate (AST) aminotransferase > 1.5 ULN concomitant with alkaline phosphatase > 2.5 ULN
Documentation of inclusion criteria adequate organ function as evidenced by the following peripheral blood counts or serum chemistry values: hemoglobin 9 gram per deciliters (g/dL), absolute neutrophil count (ANC) 1,500/L, platelet count 100,000/L, serum creatinine 1.5*the upper limit of normal (ULN), creatine phosphokinase (CPK) 2.5*ULN and adequate hepatic function as evidenced by the following serum chemistry values: total bilirubin, ULN. If total bilirubin is greater than (>) ULN, measure indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin is within normal range, participant may be eligible) ALP <= 2.5*ULN; Trabectedin: if the ALP is >2.5*ULN, then an ALP liver fraction or 5-nucleotidase must be obtained and ULN, AST and ALT 2.5 ULN will be reviewed by the Sponsor before enrollment in the OEP may occur
Patient has adequate hepatic function (serum bilirubin values <2.0 mg/dL and ALT and/or AST values <3 × the upper limit of normal ULN).
Patients enrolled with hepatic dysfunction must have laboratory test results for total bilirubin of >1.5x to <=3x the upper limit of normal (ULN) and liver function tests (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) of <8x the ULN
Alanine aminotransferase (ALT) and aspartate transaminase (AST) ?2.5*upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal (ULN) and total bilirubin < 1.5 x institutional ULN
Hepatic: total bilirubin less than or equal to (<=) 1.5 times the upper limit of the normal range (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5*ULN.
Hepatic: total bilirubin less than or equal to (<=) 1.5*the upper limit of the normal range (ULN); alanine aminotransferase (ALT) and AST <=2.5*ULN.
Screening chemistry values of the following: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ? 3.0 × upper limit of the normal (ULN), total bilirubin ? 1.5 × ULN, Creatinine ? 1.5 × ULN;
Total bilirubin =< 1.5 x upper limit of normal (ULN) except for Gilbert syndrome or cases clearly not indicative of inadequate organ function, i.e., elevation of indirect (hemolytic) bilirubin in the absence of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormality
Liver dysfunction manifested by SGTP (ALT) > 5X Upper limit of normal (ULN) and/or Aspartate aminotransferase (AST) >5 X ULN and/or direct (conjugated) bilirubin > 2X ULN
Liver function: total bilirubin < 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) < 2.5x the upper limit of normal.
Adequate organ system functions as defined below Absolute neutrophil count>=1.0x10^9/L, hemoglobin>=8.0 g/dL, platelet>=50x10^9/L, international normalized ration (INR) <=1.5, Partial thromboplastin time <=1.5xupper limit of normal (ULN), total bilirubin <=1.25xULN, alanine aminotransferase and aspartate aminotransferase<=1.5 X ULN, serum creatinine or calculated creatinine clearance<1.2XULN >=60 mL/min for Part 1;>=50 mL/minute (min) for Part 2 if data supports loosening criteria, Albuminuria<=500 mg/24h, left ventricular ejection fraction >=50%, Troponin<=1xULN, Calcium<=1.1xULN
Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin.
Elevated liver function tests (LFTs) (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP] or bilirubin levels greater than 2.5 times the normal limit) from laboratory tests conducted within 30 days prior to surgery
Patients with liver dysfunction: total bilirubin > 2.5 mg/dl; albumin < 2.5 mg/dl; alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 5 times upper limits of normal
Patients with depressed liver function, as assessed with a screening liver function test (LFT) yielding serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than the institutional upper limit of normal; or total bilirubin greater than 2 mg/dL
Have adequate organ function, including: Hepatic: Bilirubin ?1.5 × the upper limit of normal (ULN), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ?3.0 × ULN. For participants with tumor involvement of the liver, AST and ALT ?5.0 × ULN are acceptable. For participants with tumor involvement of the bone, alkaline phosphatase ?5.0 × ULN is acceptable. Renal: Serum creatinine ?2.0 × ULN. Absolute neutrophil count (ANC) ?1.0 × 109/liter (L). Hemoglobin ?9 grams per deciliter (5.58 millimoles per liter). Platelets ?90 × 109/L.
Laboratory values for hemoglobin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum creatinine or calculated/measured creatinine clearance.
Patients must have adequate hepatic and renal function as evidenced by bilirubin 2.0 times the upper limit of the normal range (ULN) or lower, alanine aminotransferase (ALT) and asparate aminotransferase (AST) 3 times the ULN or lower, serum creatinine 1.5 times the ULN or lower. Patients with nonclinically significant elevations of bilirubin up to 5.0 g/dL (85500 ?mol/L) due to known or suspected Gilbert's disease are eligible; this must be documented on the medical history page of the case report form (CRF).
Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin.
Cohort 2 (mild): Bilirubin > 1-1.5 × upper limit of the normal range (ULN) or aspartate aminotransferase (AST) > ULN, but bilirubin ? ULN
Hepatic: total bilirubin less than or equal to (<=) 1.5*the upper limit of the normal range (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5*ULN.