PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Total bilirubin =< . x institutional upper limit of normal (ULN) =<  x ULN for subjects with Gilberts 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 . mg/dL, within  weeks prior to enrollment
ELIGIBILITY CRITERIA - PHASE II (ARM D): Adequate liver function with AST/ALT less than  X upper limit of normal and total bilirubin less than  mg/dL within  days prior to first dose of study agent
Adequate liver function as demonstrated by: Total bilirubin of < upper limit of normal (ULN), Aspartate transaminase (AST) and alanine aminotransferase (ALT) ?.  ULN, Alkaline phosphatase (ALP) ?.x ULN or <x ULN if bone metastases are present, Normal serum albumin
Patients must exhibit adequate bone marrow, liver, and renal function, within \r\ndays prior to registration, defined as: \r\n* Absolute neutrophil count (ANC) >= ,/mm^ (growth factor support is permitted)\r\n* Platelets >= ,/mm^ (may be reached by transfusion)\r\n* Hemoglobin >=  gm/dl (may be reached by transfusion)\r\n* Glutamate pyruvate transaminase (GPT)/glutamate oxaloacetate transaminase (GOT) <  x upper limit of normal (ULN) (or <  x ULN in case of liver metastasis)\r\n* Bilirubin <  x ULN (or <  x ULN in case of liver metastasis)\r\n* Creatinine < . x ULN
Patients must have adequate organ and marrow function (documented within  days prior to registration) as outlined below:\r\n* Absolute neutrophil count (ANC) >= /mcl\r\n* Hemoglobin >=  g/dl\r\n* Platelets >= ,/mcl\r\n* Total bilirubin =<  x upper limit normal (ULN)\r\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum pyruvate glutamate transaminase [SPGT]) =<  x ULN\r\n* Creatinine =<  x ULN
Inlcusion criteria:\n\n        - Adult patients with histologically or cytologically confirmed cholangiocarcinoma at the\n        time of diagnosis.\n\n        Patients with cancers of the gallbladder or ampulla of Vater are not eligible.\n\n        - Patients must have received at least one prior regimen containing gemcitabine with or\n        without cisplatin for advanced/ metastatic disease. Patient should have evidence of\n        progressive disease following prior regimen, or if prior treatment discontinued due to\n        toxicity must have continued evidence of measurable or evaluable disease.\n\n        Exclusion criteria:\n\n          -  Prior or current treatment with a MEK or selective FGFR inhibitor\n\n          -  insufficient organ function\n\n               -  ANC < ,/mm [. x /L]\n\n               -  Platelets < ,/mm [ x /L]\n\n               -  Hemoglobin < . g/dL\n\n               -  Total bilirubin > .x ULN\n\n               -  AST/SGOT and ALT/SGPT > .x ULN (AST and ALT > x ULN in the presence of liver\n                  metastases)\n\n               -  Serum creatinine > .x ULN and a calculated or measured creatinine clearance <\n                   mL/min\n\n               -  Inorganic phosphorus outside of normal limits\n\n               -  Total and ionized serum calcium outside of normal limits\n\n        Other protocol-defined inclusion/exclusion criteria may apply.
Serum AST/ALT < X the upper limit of normal (ULN) for the reference lab (< X the ULN for patients with known hepatic metastases)
Evidence of significant renal, hepatic, hematologic, or immunologic disease determined by any one of the following: Estimated creatinine clearance < mL/min; ALT or AST level greater than -fold the upper limit of normal or total bilirubin greater than -fold the upper limit of normal; Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy; Thrombocytopenia; or CD+ T cell count below  cells per ?L
Clinically-significant inadequate hematological, hepatic and renal function, defined as: Neutrophil count < . x  /L and platelet count <  x ^/L; bilirubin > . x upper limit of normal (ULN); aspartate transaminase (AST) and/or alanine aminotransferase (ALT) > . x ULN or >  x ULN if patient has documented liver metastases; and serum creatinine > . x ULN
Hepatic status: Serum total bilirubin ?  x upper limit of normal (ULN; in the case of known Gilbert's syndrome, a higher serum total bilirubin [< . x ULN] is allowed), aspartate aminotransferase and alanine aminotransferase ? . x ULN, and alkaline phosphatase ? . x ULN;
Clinically significant (as determined by the investigator) hematological, hepatic and renal dysfunction, defined as: Neutrophil count < . x ^/L and platelet count <  x ^/L; bilirubin > . x ULN; AST and/or ALT > . x ULN or >  x ULN if patient has documented liver metastases; and serum creatinine > . x ULN
Adequate hepatic function, with total bilirubin ?. x upper limit of normal (ULN) (except for Gilbert Syndrome: total bilirubin < . x ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?. x ULN.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =<  x upper limit of normal (ULN) for patients receiving MAC or ALT and AST =<  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
Total bilirubin =< . x upper limit of normal (ULN) for age; participants with biliary or hepatic primaries with bilirubin values greater than . x ULN may be enrolled on study if all other eligibility criteria are met
Meet the following laboratory parameters, per the reference range, at least once during the screening period: ANC of at least /?L (Subjects may use growth factor support to achieve ANC eligibility criteria), AST and ALT not higher than  x ULN, Calculated creatinine clearance of at least  mL/min using a modified Cockcroft-Gault calculation, platelet count of at least , mm (independent of transfusion for  weeks), hemoglobin of at least . g/dL (subjects may receive blood transfusion to achieve hemoglobin eligibility criteria), and total bilirubin not higher than . x ULN (subjects with Gilbert's Syndrome may have bilirubin higher . x ULN).
Adequate bone marrow and major organ function to undergo a PBSC transplant determined within - days prior to enrollment using standard phase  criteria for organ function defined as:\r\n* Absolute neutrophil count (ANC) >= . x ^ cells/L\r\n* Platelets >=  x ^/L\r\n* Hemoglobin >=  g/dL\r\n* Aspartate and alanine aminotransferases (AST, ALT) =< . x upper limit of normal (ULN) (=<  x ULN, if documented liver metastases are present)\r\n* Total bilirubin =<  x ULN (except patients with documented Gilberts syndrome)\r\n* Creatinine <  mg/dl (or a glomerular filtration rate > )\r\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS)  or 
Adequate hepatic function as evidenced by: serum total bilirubin ?.  ULN unless considered due to Gilbert's disease, a gene mutation in UGTA (only for patients who will be receiving AG-), or leukemic involvement following approval by the study Sponsor; aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ?.  ULN, unless considered due to leukemic involvement following approval by the study Sponsor
Normal organ and marrow function: Leukocytes ? /?L, Absolute neutrophil count ? /?L, Platelets ? ,/?L, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ? . x ULN, AST(SGOT)/ALT (SGPT) ? . x institutional ULN, creatinine < . x institutional ULN
Adequate bone marrow and major organ function to undergo a PBSC transplant determined within - days prior to enrollment using standard phase  criteria for organ function defined as:\r\n* Absolute neutrophil count (ANC) >= . x ^ cells/L\r\n* Platelets >=  x ^/L\r\n* Hemoglobin >=  g/dL\r\n* Aspartate and alanine aminotransferases (AST, ALT) =< . x ULN (=<  x ULN, if documented liver metastases are present)\r\n* Total bilirubin =<  x ULN (except patients with documented Gilberts syndrome)\r\n* Creatinine <  mg/dl (or a glomerular filtration rate > )
Clinically significant kidney (e.g. glomerular filtration rate [GFR] =< ml/minute or creatinine of >=  mg/dl) or liver dysfunction (e.g. aspartate aminotransferase [AST]/alanine aminotransferase (ALT) and/or bilirubin >=  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
have adequate hepatic function, defined as having a serum total bilirubin concentration ?.mg/d, or ? 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 ?.  ULN, or ? x ULN for patients with known hepatic metastases;
For patients with Hodgkin lymphoma (HL) involvement of the liver, AST/ALT =< . x institutional ULN; total bilirubin within . x institutional ULN
Liver function: ALT and AST ? .  ULN; Total bilirubin ? .  ULN (or ?  times ULN for subjects with documented Gilbert's syndrome or for whom indirect bilirubin concentrations suggest an extra-hepatic source of elevation)
Adequate baseline organ function defined by: International Normalization Ratio (INR) and activated partial thromboplastin time (aPTT) <=.xupper limit of normal (ULN); platelet count (PLT) >=, (transfusions permitted to bring PLT to >,); total bilirubin <=.xULN (Isolated bilirubin >.xULN is acceptable if bilirubin is fractionated and direct bilirubin <% or subject has a diagnosis of Gilbert's syndrome); Alanine transaminase (ALT) <=.xULN; creatinine <=.xULN OR calculated creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or measured from  hour urine >= milliliters (mL)/minute (min); and Ejection fraction >=lower limit of normal (LLN) by Echocardiogram (ECHO) or multigated acquisition scan (MUGA)
For LY + abemaciclib only: No participants with liver metastases. Participants must have normal aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP).
Have AST, ALT, GGT, and AP that are ?.*upper limit of normal (ULN) and normal bilirubin (total and direct) regardless of liver involvement.
Adequate organ function as indicated by the following laboratory values. All laboratory tests must be obtained within  days prior to the first dose of ARQ : a. Hematological i. Absolute neutrophil count (ANC) ? . x /L ii. Platelet count (Plt) ?  x /L iii. Hemoglobin (Hb) ?  g/dL iv. International normalized ratio (INR) . to upper limit of normal (ULN) or ?  for subjects receiving anticoagulant therapy such as Coumadin or heparin b. Renal i. Serum creatinine ? . x ULN or calculated creatinine clearance ?  mL/min/. m for subjects with serum creatinine levels > . x institutional ULN c. Hepatic i. Total bilirubin ? . x ULN ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?  x ULN or ?  x ULN for subjects with known liver metastases d. Metabolic i. Glycated hemoglobin (HbAc) ? %
Adequate organ function =<  days prior to registration:\r\n* Aspartate transaminase (AST) level =< . x upper limit of normal (ULN) and alanine transaminase (ALT) =<  x upper limit of normal (ULN)\r\n* Total bilirubin level of =< . x ULN\r\n* Creatinine level =< . x ULN or creatinine clearance >  mL/min/. m^ for patients with creatinine levels above or below the institutional normal\r\n* Hemoglobin (Hgb) >=  g/dl without transfusion or epoetin dependency (=<  days prior to assessment)\r\n* Absolute neutrophil count >= . x ^/L\r\n* Platelets >=  x ^/L\r\n* Albumin >= . g/dl
Patient must meet the following laboratory values at the screening visit: Absolute Neutrophil Count ?. x /L. Platelets ? x /L. Hemoglobin (Hgb) ? g/dL. Serum creatinine <. mg/dL. Total bilirubin ?. x upper limit of normal (ULN) (isolated bilirubin >.x ULN is acceptable if bilirubin is fractionated and direct bilirubin <%). Aspartate transaminase (AST) ? . x ULN, except for patients with liver metastasis, who may only be included if AST ?. x ULN. Alanine transaminase (ALT) ? . x ULN, except for patients with liver metastasis or tumor infiltration, who may only be included if ALT ?. x ULN. Prothrombin time (PT)/International normalized ratio (INR) and Partial thromboplastin time (PTT) ?.xULN. Note: patients receiving therapeutic anticoagulation agents prior screening are permitted. Albumin . g/dL.
Adequate hepatic function, with bilirubin < . x the ULN, and AST and ALT < . x ULN
Demonstrate adequate organ function as defined: Absolute neutrophil count (ANC) ?, /mcL Platelets ?, / mcL Hemoglobin ? g/dL or ?. mmol/L without transfusion or EPO dependency (within  days of assessment) Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ?. X upper limit of normal (ULN) OR ? mL/min for subject with creatinine levels > . X institutional ULN Serum total bilirubin ? . X ULN OR Direct bilirubin ? ULN for subjects with total bilirubin levels > . ULN AST (SGOT) and ALT (SGPT) ? . X ULN OR ?  X ULN for subjects with liver metastases Albumin >. mg/dL
Adequate hepatic function with total bilirubin and ALT < .X the upper limit of normal (ULN), except in patients with Gilbert's Syndrome must have a total bilirubin < X ULN and ALT < X ULN. In cases of known liver metastases, ALT ? X ULN is acceptable (total bilirubin must be < .X ULN).
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >   ULN (>=   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
Patients with abnormal hepatic function will be eligible and will be grouped according to criteria summarized below:\r\n* Group A: Normal hepatic function\r\n** Bilirubin =< ULN\r\n** Aspartate aminotransferase (AST) =< ULN\r\n* Group B: Mild hepatic dysfunction\r\n** B: bilirubin =< ULN and AST > ULN\r\n** B: ULN < bilirubin =< . x ULN and any AST\r\n* Group C: Moderate hepatic dysfunction\r\n** . x ULN < bilirubin =<  x ULN and any AST\r\n* Group D: Severe hepatic dysfunction\r\n**  x ULN < bilirubin =<  x ULN and any AST; hepatic function tests should be repeated within  hours prior to starting initial therapy and may result in patients group assignment being altered if different to registration test results
Adequate liver function as defined below: \r\n Serum Bilirubin < . x upper limit of normal (ULN) for institution [Exception: Patients who have elevated serum bilirubin due to underlying Gilberts Syndrome or familial benign unconjugated hyperbilirubinemia are allowed.] \r\n AST (SGOT) < . x upper limit of normal (ULN) for institution (or < . x ULN in presence of liver metastases) \r\n ALT (SGPT) < . x upper limit of normal (ULN) for institution (or < . x ULN in presence of liver metastases)
Patients with adequate organ function, reflected by the following parameters: WBC ? /mcl Absolute neutrophil count (ANC) ? /mcl Platelet count ? ,/mcl SGOT, SGPT, and alkaline phosphatase ? . X upper limit of normal (ULN) Bilirubin ? . X ULN Creatinine ? institutional ULN
Hepatic: Serum/plasma total bilirubin ?. x upper limit of normal (ULN) with the exception of <. mg/dL for patients with Gilbert's disease, ALT (SGPT) and AST (SGOT) ?. x ULN.
Adequate liver function: Alanine transaminase (ALT) <  x ULN and bilirubin < . x Upper Limit of Normal (ULN), (or if bilirubin is between . -  x ULN, they must have a normal conjugated bilirubin).
Adequate liver function with serum AST, ALT and bilirubin within the normal range at the time of crenolanib commencement
Total bilirubin <  the upper limit of normal (ULN), except patients who are assigned to receive docetaxel must have liver function tests (serum transaminases, bilirubin) that are within . x the ULN
Has total bilirubin < . mg/dL, serum albumin > . gm/dL, AST and ALT < . ULN or <  x ULN for subjects with known hepatic metastases
Laboratory values: Screening serum creatinine >.upper limit of normal (ULN), alanine aminotransferase (ALT) >ULN or >ULN if liver metastases are present, total bilirubin >ULN, absolute neutrophil count (ANC) <,/mm, platelet concentration <,/mm, hemoglobin < g/dL, albumin < gm/dL.
Patients must have adequate hepatic function as evidenced by AST and ALT values ?  X ULN (?  X ULN if the liver is known to be involved by metastatic disease) and serum total bilirubin values of ? . X ULN for the reference laboratory.
Adequate organ function defined as: bilirubin <x upper limit of normal (ULN) (unless associated with Gilbert's syndrome), and ALT or AST <.x ULN.
Have serum creatinine <. mg/dL, INR < . U, absolute neutrophil count (ANC) >  x /L , platelets ?  x /L , hemoglobin ?  mg/dL, ALT and AST ?  x ULN, bilirubin ? . x ULN
Patients must have adequate Hematologic function(ANC ? ,/mcl and platelets ? ,/mcl), Renal function(serum creatinine ? ULN or calculated creatinine clearance ?  mL/min), Hepatic function(serum bilirubin ? . x ULN and AST ? . x ULN and ALT? . x ULN)
Hepatic Parameters: Total Bilirubin </= ULN; Alkaline Phosphatase </=  x ULN; AST and ALT </=  x ULN If the patient has a history of Gilbert's Syndrome, check direct and indirect bilirubin. If in the judgment of the attending medical oncologist it is safe to treat the patient, the patient will be considered eligible for this criteria.
Adequate liver function defined as total bilirubin or direct bilirubin equal to or less than . x ULN; alanine aminotransferase (ALT or SGPT) equal to or less than . x ULN ( x ULN if tumor has affected the liver)
Liver function: bilirubin > .x upper limit of normal (ULN) and SGOT (AST) > .x ULN.
Adequate baseline laboratory data: hemoglobin > g/dL, absolute neutrophil count (ANC) ?,/L, CD+ T-cells ?/L, platelets ?,/L, bilirubin ?. X upper limit of normal (ULN) or ? X ULN for patients with Gilbert's disease, serum creatinine ?. X ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ? X ULN.
Have adequate organ function, confirmed by the following laboratory values obtained ?  days prior to the first treatment: absolute neutrophil count ? .  ^/L; hemoglobin ?  g/dL; platelets ?   ^/L; aspartate transaminase and alanine transaminase ? .  upper limit of normal (ULN); serum total bilirubin ? .  ULN; serum creatinine ? .  ULN, or estimated or measured creatinine clearance ?  mL/min; prothrombin time, activated partial thromboplastin time ? .  ULN if not on anticoagulation therapy
Laboratory values: Screening serum creatinine > upper limits of normal (ULN); total bilirubin > ULN: alanine aminotransferase (ALT) and AST >/= . ULN or >/= . x ULN if liver metastases are present; absolute neutrophil count < ,/mm, platelet concentration < ,/mm, hematocrit level < % for females or < % for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) > . x ULN unless on therapeutic doses of warfarin.
Hepatic function: total bilirubin ? . x ULN (Common Terminology Criteria for AEs [CTCAE] v. grade ) except patients with Gilbert's disease (up to . mg/dL). Aspartate aminotransferase (AST) and alkaline phosphatase ? . x ULN.
Subjects with adequate organ system functions as defined follows: Absolute neutrophil count (ANC) >=. X ^/L; Hemoglobin >=. g/dL; Platelets>=  X ^/L; Total bilirubin <=.X Upper limit of normal (ULN). Isolated bilirubin >=.xULN is acceptable if bilirubin is fractionated and direct bilirubin < percent); Alanine aminotransferase (ALT) <=.X ULN; Estimated glomerular filtration rate (eGFR) >= milliliter per minute per . meter square (mL/min/m^); Spot urine (albumin/creatinine ratios [spot urine]) <  milligram per gram (mg/g) ( mg per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) >=  percent.
 Laboratory parameters (completed within  days prior to enrollment): Hematology: Absolute neutrophil count (ANC) ? . x ^/L, Platelets ?  x ^/L. Chemistry: Creatinine clearance ?  mL/min (calculated using Cockcroft Gault equation). Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < X upper limit of normal (ULN), Total bilirubin (TBL) < x ULN (unless Gilbert's disease or if liver involvement with lymphoma)
Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) < . x upper limit of normal (ULN), and total bilirubin ? . x ULN except Gilbert's Syndrome where a direct bilirubin ? . ULN will be used.
Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is =< . x ULN and ALT/AST are =< . x ULN
Must have adequate organ function as defined by the following values: white blood cells > x ^/liter(L); absolute neutrophil count (ANC) >= . x ^/L; hemoglobin >=  grams per decilitre (g/dL) subjects that required transfusion or growth factor need to demonstrate stable hemoglobin for  days of  g/dL; platelets >= x ^/L; prothrombin time (PT)/International normalized ration (INR) and partial thromboplastin time (PTT) <= . x upper limit of normal (ULN); albumin >=. g/dL; total bilirubin <=. x ULN; aspartate transaminase (AST) <=. x ULN; alanine transaminase (ALT) <=. x ULN OR < x ULN; creatinine <=. x ULN is acceptable for subjects with documented liver metastases/tumor infiltration; creatinine clearance >=  mL/min; ejection fraction>= lower limit of normal (LLN) by echocardiogram or multigated acquisition (MUGA) and minimum of % left ventricular ejection fraction (LVEF); testosterone <= nanograms per deciliter (ng/dL)
Adequate hepatic function, with bilirubin < . x the ULN, and AST and ALT < . x ULN.
Adequate bone marrow function (absolute neutrophil count > ,/mm and platelet count of > ,/mm), adequate liver function [ALT and AST < x upper limit normal (ULN), alkaline phosphatase < x ULN, and total bilirubin <. mg/dL], & adequate renal function (BUN and creatinine <. x ULN)
Participants must have adequate organ function including:\n\n               . Bone Marrow Reserve:\n\n                    . Absolute neutrophil count (ANC) ? .x^/L prior to treatment.\n                       Participants on maintenance doses of granulocyte colony stimulating factor\n                       (G-CSF) are eligible.\n\n                    . Platelets ? x^/L\n\n                    . Hemoglobin ?  g/dL\n\n                    . Use of supportive care measures (eg, use of white blood cell [WBC] growth\n                       factors, antiemetics, epoetin) should follow the ASCO guidelines as listed\n                       at www.asco.org.  Participants should receive full supportive care,\n                       including transfusion of blood as mandated by clinical need; however,\n                       transfusions administered for the sole purpose of meeting the study\n                       inclusion criteria between the time informed consent is signed and first\n                       dose of EC/placebo/PLD is administered are not allowed.\n\n               . Hepatic: Total bilirubin level < . x ULN and ALT, AST, GGT, and alkaline\n                  phosphatase levels < . x ULN.\n\n               . Renal: Serum creatinine level ? . x ULN or for participants with serum\n                  creatinine levels above . x ULN, creatinine clearance ?  mL/min/.m^\n\n               . Cardiac: Left ventricular ejection fraction (LVEF) equal to or greater than the\n                  institutional lower limit of normal.
Subjects must have adequate organ and marrow function as defined below:\n\n               . hemoglobin ?. g/dL (?. mmol/L)\n\n               . white blood cells ?,/mm(??/L)\n\n               . absolute neutrophil count ?,/mm (?.?/L)\n\n               . platelets ?,/?L (??/L)\n\n               . total bilirubin ?. upper limit of normal(ULN)\n\n               . AST/ALT/AP ?. ULN (ALT/AST ?.x ULN in case of documented liver metastases\n\n               . creatinine ?. ULN\n\n               . albumin ?. g/dL (? g/L)\n\n               . INR ?.
Subject has adequate liver function, which is defined as:  Total bilirubin is ?  mg/dL unless the increase in bilirubin is attributable to Gilbert's Syndrome  AST is ? . x upper normal limit (ULN) for age. For the purpose of this study, the ULN for AST is  U/L.  ALT is ? . x upper normal limit (ULN) for age. For the purpose of this study, the ULN for ALT is  U/L.
Subjects must have adequate hepatic function as evidenced by: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ?.  ULN, unless considered due to leukemic disease and serum total bilirubin ?. 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 ?.  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) ?.  ULN. For patients with bone metastases and/or suspected disease-related liver or biliary involvement, AST, ALT and ALP must be ?  ULN
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > . x ULN, total serum bilirubin > . x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ?. mg/dL)
Adequate liver function, defined as normal total bilirubin, ALT ?.x ULN, and AST ?.x ULN measured within  hours prior to crenolanib commencement
Inadequate organ function immediate prior to randomization including: Hemoglobin <g/dL (g/L); ANC < /mm (< . x /L); Platelets <,/mm (<  x /L); AST or ALT >. x upper limit of normal (ULN); alkaline phosphatase > . x ULN, total serum bilirubin > . x ULN; serum creatinine >. x ULN or estimated creatinine clearance <  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
S. Creat. > . x ULN.
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > . x ULN, total serum bilirubin > . x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ? . mg/dL).
Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > . x Upper Limit of Normal (ULN), total serum bilirubin > . x ULN (patients with Gilbert's Disease may be included if their total bilirubin is ?. mg/dL)
Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ? . x upper limit of normal (ULN), total bilirubin ? . x ULN, creatinine ? . x ULN.
Hepatic function: Conjugated bilirubin <.  ULN and ALT and AST <  ULN
Adequate liver function as assessed by total bilirubin ? .x upper limit of normal (ULN), and alanine transaminase (ALT) and aspartate transaminase (AST) ? .x ULN (? .x ULN in the case of liver metastases). Patients with known Gilbert's syndrome may be enrolled with total bilirubin ? . mg/dL.
total serum bilirubin ?.  ULN or ?  ULN in cases of Glibert's Syndrome or liver involvement by lymphoma
Patients must have adequate organ function: a) Bone marrow reserve: ANC ? . x /L, platelets ?  x /L, hemoglobin ?  g/dL b) Cardiac: i) QTcF <  msec on at least  of  screening ECGs. On site determination of QTcF may be used for screening purposes ii) LVEF equal to or greater than the institutional lower limit of normal. LVEF must be evaluated within  to  days prior to beginning study therapy iii) Cardiac Troponin I within normal limit (as per local institution) c) Hepatic: Total bilirubin ? . x ULN, ALT, AST ? . x ULN OR ? . x ULN for patients with liver metastases d) Renal: Serum/plasma creatinine ? . x ULN, or for patients with serum/plasma creatinine > . ULN, creatinine clearance ?  mL/min Exclusion Criteria for Part B: The presence of any of the following will exclude the patient from the study:
Screening chemistry values of the following: alanine aminotransferase (ALT) and aspartate transaminase (AST) ? .  upper limit of the normal reference range (ULN), total bilirubin ?   ULN, creatinine ? .  ULN, fasting blood glucose <  mg/dL, hemoglobin AC ? ULN, albumin ? . g/dL.
Serum direct bilirubin =< . x ULN; if considered related to ASM/MCL =<  x ULN
Patients must have adequate organ and marrow function defined as: absolute neutrophil count (ANC) >/= ,/mL, platelets >/=,/mL; creatinine clearance >/=  ml/min; total bilirubin </=  X ULN (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome); ALT (SGPT) and or AST (SGOT) </=  X ULN Exception for patients with liver metastasis: total bilirubin </=  x ULN; ALT (SGPT) </=  X ULN; Fasting lipid profile: cholesterol </=  mg/dL; triglycerides </=  mg/dL Corrected calcium >/= . mg/dL; phosphorus >/= . mg/dL for denosumab
Prior to cyclophosphamide and T cell infusions: bilirubin >= x ULN
Required Initial Laboratory Values: Leukocytes ?/ l Hemoglobin >. g/dL Platelets ?,/ l ANC ?,/mcL Serum creatinine ? . x ULN or creatinine clearance (CrCl) ?  mL/min (if using the Cockcroft-Gault formula below): Female CrCl = ( - age in years) x weight in kg x .  x serum creatinine in mg/dL Male CrCl = ( - age in years) x weight in kg x . Total Bilirubin <. mg/dl (except for subjects with Gilbert Syndrome, who can have total bilirubin < . mg/dl) SGOT (AST) <. x ULN ALP <. x ULN in absence of liver metastases (< x ULN if liver metastases present PTT <. x ULN
Adequate bone marrow, hepatic, renal and coagulation function as defined by the following: Absolute neutrophil count ?. x ^/L, Hemoglobin ?. g/dL ( g/L), Platelets ? x ^/L, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?. x upper limit of normal (ULN) (if no hepatic metastases). If hepatic tumor involvement, AST and ALT ? x ULN, Bilirubin ?. x ULN, Prothrombin time (PT) / international normalized ratio (INR) ?. x ULN, Calculated creatinine clearance > mL/min using the Cockcroft and Gault equation
Absolute neutrophil count (ANC) >=. X ^/liter (L), Hemoglobin >= grams (g)/deciliter (dL) (subjects that required transfusion or growth factor need to demonstrate stable hemoglobin for  days of  g/dL), Platelets >= X ^/L, prothrombin time (PT)/ international normalized ratio (INR) and partial thromboplastin time (PTT) - <=. X upper limit of normal (ULN); Hepatic - Albumin >=. g/dL, Total bilirubin <=. X ULN (isolated bilirubin >. X ULN is acceptable if bilirubin is fractionated and direct bilirubin <% or subject has a diagnosis of Gilbert's syndrome), Alanine aminotransferase (ALT) <=. x ULN OR < x ULN is acceptable for subjects with documented liver metastases/tumor infiltration; Renal - Creatinine <=. X ULN OR Creatinine clearance [either directly measured or calculated by Cockcroft-Gault formula] >= milliliter (mL)/minute (min); Cardiac - Ejection fraction >=% by echocardiogram or multigated acquisition scan (MUGA), Troponin (T) <=ULN, Potassium >=Lower limit of normal (LLN) and <=ULN, Magnesium >=LLN
Patients must have adequate: i. Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to ,/mcl. This ANC cannot have been induced or supported by granulocyte colony stimulating factors. Platelets greater than or equal to ,/mcl. ii. Renal function: Creatinine ? . x institutional upper limit normal (ULN). iii. Hepatic function: Bilirubin ? . x ULN. SGOT (AST) and SGPT (ALT) ? . x ULN and alkaline phosphatase ? . x ULN. iv. Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade .
Has adequate hepatic function defined as total bilirubin ?. mg/dL, unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin or ?  ULN. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? .  upper limit of normal (ULN) or ?  x ULN for subjects with known hepatic metastases.
Adequate liver function: Alanine transaminase (ALT) <  x Upper Limit of Normal (ULN) and bilirubin < . x ULN, (or if bilirubin is between .- x ULN, they must have a normal conjugated bilirubin). If liver metastases are present ALT must be <  x ULN
Major Inclusion Criteria:\n\n          . 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          . A histologically confirmed hematologic malignancy that is advanced, relapsed, or\n             refractory to standard, currently available anti-cancer treatment options\n\n          . ?  years of age\n\n          . Eastern Cooperative Oncology Group (ECOG) performance status of ?  at dose escalation\n             phase and of ?  at dose expansion phase\n\n          . Male or female patients of child-producing potential must agree to use contraception\n             or avoidance of pregnancy measures during the study and for  days after their last\n             dose\n\n          . Females of childbearing potential must have a negative serum pregnancy test\n\n          . Aspartate transaminase (AST) ? . x upper limit of normal (ULN) and alanine\n             transaminase (ALT) ? .  upper limit of normal (ULN). Patients whose disease\n             involves the liver and who have laboratory values of AST ? . ULN, AST ? . ULN, and\n             albumin ? g/L may be enrolled if agreed upon by the Principal Investigator and\n             Medical Monitor for the Sponsor\n\n          . Total bilirubin < . 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          . Life expectancy ?  months
Adequate bone marrow, liver, and renal function defined as: ) Absolute neutrophil count (ANC) greater than equal to (>=) .* ^cells/litre (L); ) Platelets >= x cells/L without transfusion support within  days prior to test; ) Hemoglobin >=  gram/deciliter (g/dL) without transfusion support within  days prior to test ) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than equal to (<=) . * upper limit of normal (ULN) ) Total bilirubin less than (<)  milligram/deciliter (mg/dL) ) Creatinine determined by serum creatinine levels <=. * ULN or a calculated creatinine clearance of >=  mL/min/. m^
The following criteria for evidence of adequate hepatic function performed within  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 . 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 . x ULN for the lab; and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than or equal to . x ULN for the lab.
Demonstrate adequate organ function as defined below, all screening labs should be performed within  days of treatment initiation\r\n* Absolute neutrophil count (ANC) >= ,/mcL\r\n* Platelets >= ,/mcL\r\n* Hemoglobin >=  g/dL\r\n* Serum creatinine =<  mg/dl OR creatinine clearance (if creatinine [Cr] >  mg/dL) >=  mL/min; creatinine clearance should be calculated per institutional standard\r\n* Serum total bilirubin =< . 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]) =< . X ULN\r\n* International normalized ratio (INR) =< . X ULN; activated partial thromboplastin time (aPTT) >= . X ULN; if on anticoagulant therapy (prothrombin time [PT] or PTT should be therapeutic)
Adequate organ function as determined by: i. Absolute neutrophil count ? . x /L (,/mm) ii.Platelet count ?  x /L (,/mm) iii.Hemoglobin ? . g/dL within first  weeks prior to first dose of investigational product iv.Calculated creatinine clearance* (CrCl) or  hour urine CrCl >  mL/min v.Total bilirubin ? . ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ?  ULN vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ? . ULN vii.Serum Electrolytes within normal limits
The following criteria for evidence of adequate hepatic function performed within  weeks prior to study entry must be met: Total bilirubin must be less than or equal to . x upper limit of normal (ULN); aspartate aminotransferase (AST) and ALT must be less than or equal to . x ULN for the lab or less than or equal to  x ULN if liver metastasis;
Hepatic and renal function meeting the strata below:\r\n* Group N: Hepatic: normal function (bilirubin =< ULN; AST =< ULN); renal: normal function (creatinine clearance [CrCl] >=  mL/min as estimated by the Cockcroft and Gault equation)\r\n* Group R: Hepatic: normal function (bilirubin =< ULN; AST =< ULN); renal: severe dysfunction (CrCl >=  and <  mL/min as estimated by the Cockcroft and Gault equation)\r\n* Group R: Hepatic: normal function (bilirubin =< ULN; AST =< ULN; renal: renal failure (hemodialysis)\r\n* Group H: Hepatic: mild dysfunction (bilirubin =< ULN; AST > ULN); renal: acceptable function (CrCl >=  mL/min as estimated by the Cockcroft and Gault equation)\r\n* Group H: Hepatic: moderate dysfunction (bilirubin > ULN and =<  x ULN; AST > ULN); renal: acceptable function (CrCl>=?  mL/min as estimated by the Cockcroft and Gault equation)\r\n* Group H: Hepatic: severe dysfunction (bilirubin >  x ULN and up to investigators discretion; AST > ULN); renal: acceptable function (CrCl >=  mL/min as estimated by the Cockcroft and Gault equation)
Adequate liver function, as evidenced by a serum bilirubin </=x the ULN (except for patients with a confirmed diagnosis of Gilbert's Disease) and an ALT or AST </=x the laboratory ULN.
Hepatic: serum total bilirubin ? . mg/dL, ALT (SGPT) and AST (SGOT) ? x upper limit of normal (ULN) at time of enrollment. If a patient has elevated liver function tests at the time of initial presentation or develops them during work-up and they are the result of a mechanical obstruction of biliary drainage by tumor compression or invasion, a biliary drain may be placed as described in NCCN Practice Guidelines in Oncology V.. If drainage allows for the liver function tests to come within inclusion criteria, the patient may be enrolled.
Acceptable hematology and serum biochemistry screening values: White Blood Cell Count (WBC) >= /mm; Absolute Neutrophil Count (ANC) >= ,/mm; Platelet (PLT) count >= ,/mm; Hemoglobin (HGB) >=  g/dl; Total bilirubin level <= . x institutional upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= . x ULN; Creatinine <= . x ULN; Albumin >  g/L
Patients must have WBC >/= . x ^/L, ANC >/= . x ^/L, platelets >/=  x ^/L, Hb >/= . g/dL); total bilirubin </= . x ULN, AST and ALT </= . x the upper limit of normal; serum potassium of >/= . mEq/L, serum albumin of >/= . g/dL, serum creatinine </= . x ULN
Adequate hepatic function as evidenced by serum bilirubin values < . mg/dL; ALT and/or AST < xULN.
Liver function tests (LFT's) =<  x upper limit of institutional normal (ULN)
Adequate hepatic function, defined as total bilirubin ?.  upper limit of normal (ULN); AST ?.  ULN; and ALT ?.  ULN. For subjects with documented metastatic disease to the liver, AST and ALT: ?  ULN.
Adequate hepatic function, defined as total bilirubin ?.  ULN; AST ?.  ULN; and ALT ?.  ULN.
. x ULN
Adequate bone marrow, liver & renal function as assessed by the following laboratory requirements to be conducted w/in  days prior to start of first dose: Hemoglobin >/= . g/dL; Absolute neutrophil count (ANC) >/= ,/mm^; Platelet count >/= ,/mm^; Total bilirubin </= . times the upper limit of normal (ULN);ALT and AST </= . x ULN (</=  x ULN for pts w/ liver involvement); INR </= . and PTT w/in normal limits
If organ function abnormalities are considered due to leukemic infiltration, total bilirubin must be =<  x ULN
Patient's total bilirubin must be ? . x ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible. Cardiac Function:
Hepatic: serum total bilirubin ? . mg/dL, ALT (SGPT) and AST (SGOT) ? x upper limit of normal (ULN) at time of enrollment. If a patient has elevated liver function tests at the time of initial presentation or develops them during work-up and they are the result of a mechanical obstruction of biliary drainage by tumor compression or invasion, a biliary drain may be placed as described in NCCN Practice Guidelines in Oncology V.. If drainage allows for the liver function tests to come within inclusion criteria, the patient may be enrolled.
Adequate hepatic function (total bilirubin ? .x ULN; AST and ALT ? x ULN).
Hepatic function: Total bilirubin < .  upper limit of normal (ULN) (except in the case of subjects with known Gilbert's disease: <   ULN) and transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) <   ULN based on age- and institution specific laboratory-specific normal ranges
Adequate baseline organ function defined by the criteria below: total bilirubin =< .x 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 =< .xULN; creatinine =< .xULN
Adequate bone marrow function [absolute neutrophil count (ANC) > ,/mm & platelet count of > ,/mm], adequate liver function [alanine aminotransferase (ALT) & aspartate aminotransferase (AST) < x upper limit normal (ULN), alkaline phosphatase < x ULN, & total bilirubin <. mg/dL], & adequate renal function (BUN & creatinine <. x ULN)
Bilirubin >  x ULN which cannot be attributed to MCC metastasis
Have adequate marrow and organ function as defined in Table . Table  Laboratory Values SYSTEM LABORATORY VALUES Hematologic ANC ?. x /L Hemoglobin ? g/dL (after transfusion if needed) Platelets ? x /L Hepatic Albumin ?. g/dL Serum bilirubin ?. x ULN unless due to Gilbert's syndrome AST and ALT ? x ULN Renal Calculated creatinine clearance* ?  mL/min Serum Creatinine ?. mg/dL or .?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) >= . gram/decilitre (dL), absolute neutrophil count (ANC) >= /microliter (mcL), platelet >= ,/micL, aspartate aminotransferase/alanine transaminase (AST/ALT) <=  x Upper Limit of Normal (ULN), total Bilirubin <=  x ULN, creatinine <=  x ULN.
Adequate hepatic function as evidenced by: serum total bilirubin ?.  upper limit of normal (ULN), unless considered due to Gilbert's disease, a gene mutation in UGTA, or disease involvement, following approval by the Medical Monitor; AST, ALT, ALP ?.  ULN, with the exception of subjects with bone metastases and/or suspected disease-related liver or biliary involvement, where ALP must be ?  ULN
Adequate baseline organ function defined as: absolute neutrophil count >= . x ^/Liter (L); hemoglobin>= gram per deciliter (g/dL); platelets >=  x ^/L; prothrombin time /international normalized ratio and partial thromboplastin time =<. x ULN; serum bilirubin=<. times upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase =<. times ULN; serum creatinine=<. mg/dL or calculate creatinine clearance >=  milliliter per minute; Left ventricular ejection fraction>= lower limit of normal by echocardiography.
Laboratory values: Screening serum creatinine >. x upper limit of normal (ULN), alanine aminotransferase (ALT) >ULN or >ULN if liver metastases are present, total bilirubin >ULN, absolute neutrophil count (ANC) <,/mm, platelet concentration <,/mm, hemoglobin <g/dL.
Hepatic: total bilirubin ? . X ULN, ALT and AST ? ULN;
Must have adequate bone marrow and renal/hepatic function at the screening visit (? days preceding the lab assessment): i. ANC ? ,/mm, without G-CSF ii. Platelets ? ,/mm, without transfusion iii. Hemoglobin ?  g/dL, without transfusion support iv. AST or ALT ?   ULN v. Total serum bilirubin ? . times ULN vi. Serum creatinine ? ULN vii. Potassium and magnesium levels within normal limits. If below the lower limit of normal, must have levels corrected by supplementation prior to starting study drug. viii. albumin > . g/dL
Have adequate baseline organ function defined by the following criteria: Total bilirubin <=. 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 <= x ULN. Serum Creatinine <=. x ULN.
Must have adequate organ function as defined by the following baseline values: Absolute neutrophil count >=. x ^/Liter, Hemoglobin >= gram (g)/decilitre(dL), Platelets >= x ^/L, Partial thromboplastin time (PTT) <=. x upper limit of normal (ULN), Albumin >=. g/dL, Serum total bilirubin <=. times ULN (for Arm B: <=ULN ), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <=. times ULN (for Arm B: <=. times ULN), Serum Creatinine <=. x ULN, Or Measured or Calculated Creatinine Clearance >= mL/min (Arm A or B), >= mL/min (Arm C), Left ventricular ejection fraction >=% by ECHO.
Adequate baseline organ function as defined by: absolute neutrophil count (ANC) >= .  /L; Hemoglobin >=  g/dL; Platelet count >=  x /L; prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) <= . x upper limit of normal (ULN); Albumin >= . g/dL; Total bilirubin <= . x ULN; aspartate aminotransferase (AST) and alanine transaminase (ALT) <= . x ULN; Creatinine <=. mg/mL; Left Ventricular Ejection fraction (LVEF) >= lower limit of normal (LLN) by ECHO
Must have adequate organ function as defined by the following values: renal function -  hr creatinine clearance (revised Schwartz formula), or radioisotope glomerular filtration rate (GFR) >= milliliter (mL) per minute per . meter square (mL/min/.m^); or a serum creatinine <=upper limit of normal (ULN) for age and gender; liver functions as bilirubin (sum of conjugated + unconjugated) <=. x ULN for age, alanine aminotransferase (ALT) <=. x ULN; for the purposes of enrollment and toxicity monitoring the ULN for ALT will be  unit per liter (U/L); cardiac function - corrected QT (QTcB) interval < milliseconds (msec), left ventricular ejection fraction (LVEF) >=lower limit of normal (LLN) by ECHO.
Adequate hepatic function, defined as AST and ALT ?.X ULN and serum direct bilirubin ?.X ULN. Exceptions may be made for patients with elevated liver transaminases secondary to AML after discussion with the Medical Monitor
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 . x ULN; Trabectedin: if the ALP is >. x ULN, then an ALP liver fraction or -nucleotidase must be obtained and ULN, AST and ALT . ULN
Documentation of inclusion criteria adequate organ function as evidenced by the following peripheral blood counts or serum chemistry values: hemoglobin  gram per deciliters (g/dL), absolute neutrophil count (ANC) ,/L, platelet count ,/L, serum creatinine .*the upper limit of normal (ULN), creatine phosphokinase (CPK) .*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 <= .*ULN; Trabectedin: if the ALP is >.*ULN, then an ALP liver fraction or -nucleotidase must be obtained and ULN, AST and ALT . ULN will be reviewed by the Sponsor before enrollment in the OEP may occur
Patient has adequate hepatic function (serum bilirubin values <. mg/dL and ALT and/or AST values <  the upper limit of normal ULN).
Adequate laboratory values. a) Hemoglobin >/= gm/dL. b) White blood cell count (WBC) >/= /L. c) Absolute neutrophil count (ANC) >/= /L. d) Platelet count >/=,/L. e) PT </= . x upper limit of normal (ULN). f) Activated partial thromboplastin time (aPTT) </= . x ULN. g) AST </=. x ULN. h) ALT </= . x ULN. i) Total bilirubin </= . x ULN. j) Creatinine </=. x ULN.
Standard safety inclusion for serum creatinine, AST, ALT, bilirubin
Hepatic and renal function meeting the strata as outlined below; nota bene (NB): patients must fulfill both total bilirubin and serum glutamic-oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) criteria and creatinine function to be included in a group; however, if a patients total bilirubin and SGOT/AST and creatinine levels indicate different groups, the patient may be enrolled in the indicated group with the greatest degree of liver dysfunction; all liver and renal function tests must be completed within  hours prior to the start of treatment; Note: patients on dialysis will not be eligible\r\n* Group A: hepatic function: normal function (bilirubin =< upper limit of normal [ULN]; AST =< ULN); renal function: normal function (creatinine clearance [CrCl] >=  mL/min) \r\n* Group B: hepatic function: normal function (bilirubin =< ULN; AST =< ULN); renal function: moderate dysfunction (CrCl >=  and <  ml/min)\r\n* Group C: hepatic function: normal function (bilirubin =< ULN; AST =< ULN); renal function: severe dysfunction (CrCl >=  and <  ml/min)\r\n* Group D: hepatic function: mild dysfunction D: bilirubin =< ULN; AST > ULN, D: bilirubin > ULN and =< . x ULN; any AST; renal function: normal function (creatinine clearance [CrCl] >=  mL/min)\r\n* Group E: hepatic function: mooderate dysfunction (bilirubin . x > ULN and =<  x ULN; any AST); renal function: normal function (creatinine clearance [CrCl] >=  mL/min)\r\n* Group F: hepatic function: severe dysfunction (bilirubin >  x ULN and up to investigators discretion; any AST); renal function: normal function (creatinine clearance [CrCl] >=  mL/min)
Screening chemistry values of the following: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ? .  upper limit of the normal (ULN), total bilirubin ? .  ULN, Creatinine ? .  ULN;
Total bilirubin =< . 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
Adequate organ system functions as defined below Absolute neutrophil count>=.x^/L, hemoglobin>=. g/dL, platelet>=x^/L, international normalized ration (INR) <=., Partial thromboplastin time <=.xupper limit of normal (ULN), total bilirubin <=.xULN, alanine aminotransferase and aspartate aminotransferase<=. X ULN, serum creatinine or calculated creatinine clearance<.XULN >= mL/min for Part ;>= mL/minute (min) for Part  if data supports loosening criteria, Albuminuria<= mg/h, left ventricular ejection fraction >=%, Troponin<=xULN, Calcium<=.xULN
Patients with abnormal liver function will be eligible and will be grouped according to the criteria below\r\n* Group A (normal hepatic function)\r\n** Bilirubin =< upper limit of normal (ULN) and aspartate aminotransferase (AST) =< ULN\r\n* Group B (mild hepatic dysfunction)\r\n** B: bilirubin =< ULN and AST > ULN\r\n** B: bilirubin > ULN but =< . x ULN and any AST\r\n* Group C (moderate hepatic dysfunction)\r\n** Bilirubin > . x ULN to =<  x ULN and any AST\r\n* Group D (severe hepatic dysfunction) \r\n** Bilirubin >  x ULN and up to investigators discretion and any AST\r\n* Patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes; registration laboratory investigations will be used to assign a patient to a hepatic function group; liver function tests should be repeated within  hours prior to starting initial therapy and may result in the patients' group assignment being altered if different to registration test results
Aspartate aminotransaminase (AST) =< . x upper limit of normal (ULN) (=< . x in case of liver [metastases] mets), within  weeks prior to study start
Have adequate organ function, including: Hepatic: Bilirubin ?.  the upper limit of normal (ULN), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ?.  ULN. For participants with tumor involvement of the liver, AST and ALT ?.  ULN are acceptable. For participants with tumor involvement of the bone, alkaline phosphatase ?.  ULN is acceptable. Renal: Serum creatinine ?.  ULN. Absolute neutrophil count (ANC) ?.  /liter (L). Hemoglobin ? grams per deciliter (. millimoles per liter). Platelets ?  /L.
AP ? . x ULN (?  x ULN if disease-related).
Cohort  (mild): Bilirubin > -.  upper limit of the normal range (ULN) or aspartate aminotransferase (AST) > ULN, but bilirubin ? ULN
Cohort  (normal hepatic function): Bilirubin ? ULN; AST ? ULN