Clinically significant or uncontrolled cardiac disease.
Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ? Grade 2 dyspnea, according to CTCAE 4.03)
Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results history
Current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic examination.
No clinically significant infections as judged by the treating investigator
N2 or N3 disease detected clinically or by imaging
Any significant medical complications related to induction must have resolved
Any significant medical complications related to therapy must have resolved
No signs of clinically significant hearing loss
Patients with clinically significant history of any chronic liver disease.
Significant abnormalities on ECG at Screening
Subject has clinically significant and uncontrolled major medical condition(s) including but not limited to:
Serious co-morbid medical conditions, including clinically-significant cardiac disease
Uncontrolled (over the last 30 days), clinically significant confounding medical conditions
Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator;
History of clinically significant, medically unstable disease which, in the judgment of the investigator, would jeopardize the safety of the subject, interfere with trial assessments or endpoint evaluation, or otherwise impact the validity of the trial results.
Uncontrolled clinically significant arrhythmias.
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
Has a medical history of clinically significant lung disease
Significant myelofibrosis (>2+fibrosis)
Clinically significant anemia due to non-MDS etiologies
Treatment with clinically significant metabolic CYP3A inducers within 14 days before the first dose of study drug; clinically significant CYP3A inducers are not permitted during the study
Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
Clinically significant gastrointestinal disorders.
History of clinically significant cardiac dysfunction
History of malabsorption or other clinically significant metabolic dysfunction that may interfere with absorption of oral study treatment
Known clinically significant liver disease
Participant has clinically significant uncontrolled conditions.
Urinalysis: o No clinically significant abnormalities
History of clinically significant coagulation or platelet disorder in the past 12 months.
Clinically significant cardiac disease.
Current diagnosis of any other active or clinically significant nonbreast cancer
Clinically confirmed as postmenopausal.
History of clinically significant thrombosis within the past 3 months prior to randomization that, in the investigator's opinion, may place the patient at risk of side effects from anti-angiogenesis products.
History of clinically significant glomerulonephritis, biopsy-proven tubulointerstitial nephritis, crystal nephropathy, or other renal insufficiencies.
Known significant clinically significant gastrointestinal disease
History of clinically significant cardiac dysfunction
Clinically significant gastrointestinal bleeding within 6 months prior to the first dose of ALRN-6924
Clinically significant third-space fluid accumulation
Known clinically significant liver disease
Evidence of increased intracranial pressure (clinically significant papilledema, vomiting, and nausea, or reduced level of consciousness)
Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours;
Have any clinically significant disease considered by the investigator to interfere with study participation
History of clinically significant cardiac disease; uncontrolled hypertension
Has clinically significant heart disease that affects normal activities.
Clinically significant cardiac disease
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the subject in the study
Evidence of clinically significant immunosuppression.
Clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders.
Clinically significant bleeding event, as judged by investigator, within prior 6 months
Clinically significant hearing impairment, as judged by the Principal Investigator.
History of clinically significant GI bleed, intestinal obstruction, or GI perforation within 6 months of study dose
History of malabsorption or other clinically significant metabolic dysfunction
History of clinically significant cardiac or pulmonary dysfunction as specified in antecedent study
Have any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (eg, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).
History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion
Significant screening ECG abnormalities.
Any known clinically significant prior radiation to the chest area that included lung parenchyma.
Cardiac ejection fraction >= 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
Current, clinically significant, active infection that in the opinion of the Investigator would make them an unfit participant in the trial
Women who have had an abnormal gynecology exam within the last three years with clinically significant findings, such as secondary dysmenorrhea, polyps, or atypia, which in the opinion of the Investigator would interfere with the study.
Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
Known clinically significant liver disease,
History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
EXCLUSION - TREATMENT: Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6
Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
Clinically significant gastrointestinal disorders
Clinically significant history of liver disease
Patients with any clinically significant unrelated systemic illness that would compromise the patient’s ability to tolerate protocol therapy
Clinically significant anemia, neutropenia or thrombocytopenia at screening
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that will likely interfere with the study procedures or results
Patients with clinically significant abnormalities on urinalysis at < 14 days prior to randomization.
Other clinically significant comorbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
Medically significant (symptomatic) bradycardia
Significant ECG abnormalities.
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
History of clinically significant cardiac dysfunction
History of malabsorption or other clinically significant metabolic dysfunction
History of autoimmune disease, clinically significant cardiac or pulmonary dysfunction
Have evidence of active clinically significant bleed (e.g., gastrointestinal bleed, hemoptysis, or gross hematuria) at screening
Clinically significant active infection, in the judgment of the investigator
Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers) as assessed by the principal investigator during screening and during the study
Clinically significant cardiac disease.
Patients with acute or chronic hepatic dysfunction as evidenced by clinically significant abnormalities in albumin, total protein, or prothrombin time, or evidence of hepatic injury with clinically important (> grade 1) changes in AST, ALT, ALP, bilirubin, or GGT values.
Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)
COHORT I: No significant contraindications to cisplatinum chemotherapy (significant hearing loss, renal dysfunction or neuropathy)
Active or clinically significant cardiac disease.
Clinically significant active infection or uncontrolled medical condition
History of clinically significant or uncontrolled cardiac disease including but not limited to:
Clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic or neurological conditions.
Subject who has a clinically significant coagulation disorder or disease, defined as a platelet count <100,000 per microliter, International Normalized Ratio >1.5, or a PTT more than 1.5 times outside the laboratory's normal reference range;
Has a clinically significant coagulopathy per investigator’s assessment
History of clinically significant cardiac dysfunction
Malignant ascites that is clinically detectable by physical examination or is symptomatic; evidence of radiographic ascites that is not clinically significant will not be an exclusion criterion
Patients with any clinical significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that is likely to interfere with the study procedures or results
Taking a medication known to be clinically significant P-gp inhibitors or inducers within 14 days of treatment with Oratecan.
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study
Impaired cardiac function including any of the following:\r\n* Myocardial infarction within 6 months of starting study drug\r\n* A past medical history of clinically significant electrocardiography (ECG) abnormalities, including corrected QT (QTc) 481 ms or greater\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Must have a normal ejection fraction (within the reference range of the institution) and no clinically significant valvular dysfunction.
Clinically significant patient history which in the judgment of the principal investigator would compromise the patient’s ability to tolerate high-dose
Any of the following ECG findings or assessments including: Baseline QTcF interval >=450 milliseconds; Clinically significant ECG assessments should be reviewed by the site cardiologist prior to study entry.
Evidence of increased intracranial pressure (clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
Clinically significant, uncontrolled heart disease
Clinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune disease
Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the judgment of the principal or associate investigator would compromise the patient’s ability to tolerate this therapy or are likely to interfere with the study procedures or results
No clinically significant infections as judged by the treating investigator
Known or suspected clinically significant active bleeding.
TREATMENT WITH SJCAR19: Electrocardiogram (EKG) without evidence of clinically significant arrhythmia
Significant screening ECG abnormalities
Clinically significant patient history which in the judgment of the principal investigator (PI) would compromise the patients’ ability to tolerate high-dose aldesleukin.
Subject has an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically significant and would preclude study participation.
Have electrocardiogram (ECG) with no clinically significant findings as assessed by the investigator performed within 28 days prior to first dose;
Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea, or reduced level of consciousness)
Evidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema)
Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality as determined by the investigator.
The patient has any pre-existing coagulopathy, recent hemoptysis, gross hematuria, or gastrointestinal bleeding, and a history of a clinically significant cardiovascular or cerebrovascular event within 12 months prior to study entry
Significant cardiopulmonary dysfunction
Known clinically significant liver disease
Known clinically significant liver disease
Ongoing clinically significant infection at or near the incident lesion
Participants with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities
STRATUM A: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, gastrointestinal [GI] disease, or other organ dysfunction) that in the investigator’s judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results
STRATUM B: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ dysfunction) that in the investigator’s judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results
STRATUM C: Participants with other clinically significant medical disorders (serious infections or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ dysfunction) that in the investigator’s judgment could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results
Participants may not have current or history of clinically significant muscle disorders (eg, myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the study.
Significant gastrointestinal disease
Patients must not have clinically significant cardiac disease.
Clinically significant cardiac disease
History of significant cerebrovascular disease
Concurrent clinically significant infections as determined by the treating Investigator.
Has clinically significant lung disease or is suspected to have such diseases by imaging at Screening
Has clinically significant corneal disease
Treatment with clinically significant metabolic inducers within 14 days before the first dose of study drug; clinically significant metabolic inducers are not permitted during the study
Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
Cardiac ejection fraction ? 50%, no evidence of pericardial effusion, and no clinically significant arrhythmias
Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), likely interfere with the study procedures or results
History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
Documented clinically significant cardiac arrhythmias
Clinically significant abnormal laboratory results
Current, serious, clinically significant cardiac arrhythmias as determined by the investigator, or patient receiving a digitalis derivative.
Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this study
The subject has experienced any of the following:\r\n* Clinically significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Clinically significant hemoptysis within 3 months of the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the start of study treatment
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction
All persistent clinically significant toxicities from prior chemotherapy must be less than or equal to grade 1
No clinically significant infections as judged by the treating investigator
Any clinically significant uncontrolled concomitant disease
Cardiac ejection fraction >= 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
Uncontrolled clinically significant arrhythmia, myocardial ischemia or congestive heart failure within the past 2 weeks, that is considered by the treating physician as a contraindication for initiation of chemotherapy;  discussion with the principal investigator is encouraged if further clarification is required
Has any other clinically significant abnormal laboratory value in the opinion of the investigator
Active or clinically significant cardiac disease
clinically significant cardiac disease
clinically significant active infection
clinically significant CNS disorder
Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.
Known impaired cardiac function including any of the following:\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias;\r\n* Clinically significant resting bradycardia (< 50 beats per minute);\r\n* Myocardial infarction within 1 year of starting study drug;\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
Symptoms of a clinically significant illness that may place the subject at risk by trial participation or influence the outcome of the trial in the four weeks before first treatment and during the trial;
Patients on every 2, 3 or 4 week systemic therapy programs must be off the treatment program for at least 2, 3, or 4 weeks, respectively, and must have recovered from any clinically significant toxicity experienced; patients on weekly or daily systemic therapy programs and patients receiving radiation must be at least 1 week since treatment and recovered from any clinically significant toxicity experienced; must be at least 4 weeks and have recovered from major surgery
If present, clinically significant or symptomatic amounts of ascites should be drained prior to Day 1.
Subjects with clinically significant uncontrolled cardiac disease
Clinically significant dry eye or contact lens use
Patients with any clinically significant autoimmune disease uncontrolled with treatment
Cardiac ejection fraction ? 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings
Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.
Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment.
Active or clinically significant Gastric Antral Vascular Ectasia (GAVE, \watermelon stomach\)
Clinically significant ascites defined as requiring ? 1 paracentesis every 2- weeks
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection, or any other condition that could compromise participation of the participant in the study.
Medically significant (symptomatic) bradycardia.
Clinically significant cardiac disease
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study
Patients with significant malabsorption as determined by the treating physician
Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this study (CYP3A4/5 inducers)
Either clinically positive (N1 only) or clinically negative axillary nodes (N0)
No clinically significant infections or any other medical condition(s) that render the subject ineligible for high dose IL-2 therapy as judged by the treating investigator
Any clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the study
Has clinically significant toxicities from previous anti-cancer therapy that have not resolved, or have not stabilized at a new baseline
History of clinically significant auditory or ocular toxicity with ICT
Urinalysis: No clinically significant abnormalities
Patients with clinically significant cardiomyopathy requiring treatment
History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
No clinically significant uncontrolled infections as determined by investigator
Patients must not have clinically significant malabsorption syndrome or history
No clinically significant infections as judged by the treating investigator
Urinalysis: No clinically significant abnormalities
Ongoing clinically significant anemia due to factors such as known iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the study
Clinically significant unrelated systemic illness (including but not limited to active life threatening infection, cardiac or neurologic events, current hospital admission for a coexisting comorbid illness), which would make it impossible for the patient to tolerate re-irradiation or systemic chemotherapy or likely to interfere with the results
EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, clinically significant hypotension, symptomatic coronary artery disease, or a documented ejection fraction of < 45%; any patient with an EF of 45-49% must receive clearance by a cardiologist to be eligible for the trial
EXCLUSION CRITERIA FOR TNBC: Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, clinically significant hypotension, symptomatic coronary artery disease or a documented ejection fraction of < 45%; any patient with an EF of 45-49% must receive clearance by a cardiologist to be eligible for the trial
Complete blood count (CBC) - no clinically significant findings
Complete metabolic profile (CMP) - no clinically significant findings
Lactate dehydrogenase (LDH) - no clinically significant findings
History of clinically significant gastrointestinal bleeding, colitis, or gastrointestinal perforation.
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study
Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), clinically significant pulmonary disease (such as ? Grade 2 dyspnea, according to CTCAE 4.03).
History or evidence of other clinically significant disorders that would pose a risk to subject safety.
Uncontrolled clinically significant cardiac arrhythmia
uncontrolled or clinically significant conduction abnormalities; first degree AV block or asymptomatic LAFB/RBBB are eligible
Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
Clinically significant, uncontrolled heart diseases.
Concurrent, clinically significant, active malignancies within 12 months of study enrollment
Clinically significant hematemesis or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (such as pulmonary hemorrhage) within 4 weeks of enrollment
Clinically significant abnormalities found on an ECG.
Clinically significant or uncontrolled cardiac disease.
History of clinically significant (as determined by the treating physician) atrial arrhythmia or any history of ventricular arrhythmia
Clinically significant cardiac disease
Inclusion Criteria:\n\n        All Patients (Stages 1 and 2):\n\n          1. The patient is ?18 years old\n\n          2. The patient has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2\n\n          3. The patient has adequate baseline organ function, including cardiac, renal, and\n             hepatic function:\n\n               -  Left ventricular ejection fraction (LVEF) ? institutional lower limit of normal\n                  as measured by multigated acquisition scan or 2-dimensional (2-D) echocardiogram\n                  within 28 days prior to start of therapy and no clinically significant\n                  abnormalities on a 12-lead electrocardiogram (ECG)\n\n               -  Serum creatinine ?1.5 mg/dL (or ?114 µmol/L)\n\n               -  Serum albumin ?3.2 g/dL (or ?32 g/L) in the absence of receipt of (IV) albumin\n                  within the previous 72 hours\n\n               -  Bilirubin ?1.5 mg/dL (or ?26 µmol/L)\n\n               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ?2.5 times the upper\n                  limit of normal (ULN)\n\n               -  CPK ?2.5 times the ULN\n\n          4. If a woman of child bearing potential, the patient has a negative serum or urine\n             pregnancy test within 1 week prior to SL-401 treatment (intervals shorter than 1 week\n             are acceptable, if required by institutional guidelines)\n\n          5. The patient has signed informed consent prior to initiation of any study-specific\n             procedures or treatment\n\n          6. The patient is able to adhere to the study visit schedule and other protocol\n             requirements, including follow-up for response assessments\n\n          7. The patient agrees to use acceptable contraceptive methods for the duration of time in\n             the study, and to continue to use acceptable contraceptive methods for 2 months after\n             the last SL-401 infusion\n\n          8. Patient has an absolute neutrophil count (ANC) ?0.5×10?/L\n\n        Additional Inclusion Criteria Specific to Patients with MF and CMML (Stages 1 and 2)\n\n        Exclusion Criteria:\n\n        All Patients (Stages 1 and 2):\n\n          1. Patient has persistent clinically significant toxicities Grade ?2 from previous\n             chemotherapy not readily controlled by supportive measures (excluding alopecia,\n             nausea, and fatigue)\n\n          2. Patient has received treatment with chemotherapy, wide-field radiation, or biologic\n             therapy within 14 days of study entry\n\n          3. Patient has received treatment with another investigational agent within 14 days of\n             study entry or concurrent treatment with another investigational agent.\n\n          4. Patient has previously received treatment with SL-401 or has a known hypersensitivity\n             to any components of the drug product\n\n          5. Patient has an active malignancy and/or cancer history (excluding myeloproliferative\n             disorders and concomitant myeloid malignancies as specified in the inclusion criteria)\n             that can confound the assessment of the study endpoints. Patients with a past cancer\n             history (within 2 years of entry) and/or ongoing active malignancy or substantial\n             potential for recurrence must be discussed with the Sponsor before study entry.\n             Patients with the following neoplastic diagnoses are eligible: non-melanoma skin\n             cancer, carcinoma in situ (including superficial bladder cancer), cervical\n             intraepithelial neoplasia, or organ-confined prostate cancer with no evidence of\n             progressive disease\n\n          6. Patient has clinically significant cardiovascular disease (e.g., uncontrolled or any\n             New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina,\n             history of myocardial infarction or stroke within 6 months of study entry,\n             uncontrolled hypertension or clinically significant arrhythmias not controlled by\n             medication)\n\n          7. Patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic\n             obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's\n             opinion, would put the patient at significant risk for pulmonary complications during\n             the study\n\n          8. Patient has known active or suspected disease involvement of the central nervous\n             system (CNS). If suspected due to clinical findings, CNS disease should be ruled out\n             with relevant imaging and/or examination of cerebrospinal fluid\n\n          9. Patient is receiving immunosuppressive therapy, with the exception of corticosteroids\n             as specified in the inclusion criteria and tacrolimus, for treatment or prophylaxis of\n             graft-versus-host disease (GVHD). If the patient has been on immunosuppressive\n             treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at\n             least 14 days prior to study drug and there must be no evidence of Grade ?2 GVHD\n\n         10. Patient has uncontrolled intercurrent illness including, but not limited to,\n             uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness\n             that would limit compliance with study requirements\n\n         11. Patient is pregnant or breast feeding\n\n         12. Patient has known human immunodeficiency virus (HIV)\n\n         13. Patient has evidence of active or chronic Hepatitis B or Hepatitis C infection.\n\n         14. Patient is oxygen-dependent\n\n         15. Patient has any medical condition that in the Investigator's opinion place the patient\n             at an unacceptably high risk for toxicities\n\n        Additional Exclusion Criteria Specific to Patients with MF and CMML (Stages 1 and 2)
Clinically significant medical disorders that could compromise the ability to tolerate protocol therapy or that would interfere with the study procedures or results history
Subject has a clinically significant uncontrolled condition(s) s described in the protocol.
ARM B COHORT 3: Patients must not have active clinically significant hemoptysis
Subject has a clinically significant peripheral artery disease, e.g., those with claudication, within 6 months
Patients must have recovery from other clinically significant, non-hematologic toxicities to =< grade 2
Has any clinically significant infection
Patients with clinically significant unrelated systemic illness (including autoimmune disease, serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the principal or associate investigators would compromise the patient’s ability to tolerate this therapy or are likely to interfere with the study procedures or results
Patients with clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
Patients with history of clinically significant bleeding disorder
Significant organ dysfunction defined as:
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
Clinically significant uncontrolled illness
Patients with any clinically significant autoimmune disease uncontrolled with treatment
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT interval (QTc) > 480 msec on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Research participants without clinically significant encephalopathy/new focal deficits
Clinically significant heart disease
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Fridericia QT (QTcF) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C), if deemed clinically significant by the treating physician.
Clinically significant gastrointestinal disorders
Clinically significant abnormalities in laboratory test results (including complete blood count, chemistry panel including electrolytes, and urinalysis)
Clinically significant coagulation disorder
Patients with any amount of clinically significant pericardial effusion
Clinically significant comorbid disease or other underlying condition, including major autoimmune disorders that would contraindicate study therapy or confuse interpretation of study results
Clinical evidence of significant renal impairment
Clinically significant electrolyte disorders including sodium < 130 or > 145 and/or potassium < 3.0 or > 5.5 and/or magnesium < 1.8 or > 2.9
Patient has a history or current evidence of clinically significant heart disease including:\r\n* Clinically significant congestive heart failure, unstable angina pectoris\r\n* Clinically significant cardiac arrhythmia\r\n* Myocardial infarction during the last 6 months, and/or a current electrocardiogram (ECG) tracing that is abnormal in the opinion of the treating Investigator\r\n* Corrected QT interval (QTc) prolongation > 480 msec (Bazett's formula)\r\n* Congenitally long QT syndrome, and/or current anti-arrhythmic therapy, and / or has received any marketed or experimental compound in the last 1 week prior to entering the study with known effects of QT prolongation
Patient with evidence of clinically significant bradycardia (heart rate [HR] < 50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree atrioventricular (AV) block (Mobitz type 2), patient with uncontrolled hypertension (>= 140/90 mmHg). Patients who are controlled on antihypertensive medication will be allowed to enter the study
History of clinically significant coagulopathy
Clinically significant comorbid disease or other underlying condition, including major autoimmune disorders that would contraindicate study therapy or confuse interpretation of study results
Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complications
Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
History of clinically significant ventricular arrhythmias
History of clinically significant (as determined by the treating physician) atrial arrhythmia;
History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
Respiratory Function: Adequate respiratory function in the opinion of the Investigator with no clinically significant uncontrolled respiratory disease.
Concurrent or Intercurrent Illness: Impaired wound healing due to diabetes; Significant concurrent or intercurrent illness, psychiatric disorders or alcohol or chemical dependence that would compromise Subject safety or compliance or interfere with interpretation of the study; Uncontrolled thyroid disease or cystic fibrosis; Presence of clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological (with the exception of the presence of hepatitis B virus (HBV), viral hepatitis, or cirrhosis), endocrine, or central nervous system disorders; Current encephalopathy or current treatment for encephalopathy; Variceal bleeding requiring hospitalization or transfusion within 4 months of screening; History of human immunodeficiency virus or acquired immune deficiency syndrome; The clinical presence of ascites.
Serum bilirubin =< 2 x ULN or considered not clinically significant
Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions
Evidence of clinically significant neuropathy (> Grade 1) by physical exam.
Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions such as congestive heart failure
History of clinically significant cardiac disease
Clinically significant iron metabolism disorders (eg, sickle cell anemia)
Any Grade 3 or higher lab abnormalities should be discussed and approved by the Medical Monitor prior to enrollment (even if not considered clinically significant);
Clinically significant heart disorders including an ejection fraction of < 50%
Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his/her participation in this study
Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this study
Symptomatic, clinically significant autonomic neuropathy which the Principal Investigator (PI) feels will preclude administration of study treatment
Has clinically significant corneal disease
Clinically significant, uncontrolled heart diseases
Electrocardiogram (EKG) without clinically significant abnormality
Clinically significant abnormality on ophthalmologic examination during screening evaluation
Clinically significant, uncontrolled heart diseases.
Clinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PI
Clinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PI
Evidence of clinically significant pancreatitis as determined by the investigator
Any significant ophthalmologic abnormality
Significant gastrointestinal abnormalities,
Clinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be given
Urinalysis: No clinically significant abnormalities.
Have significant baseline neuropathies
Clinically significant abnormal 12-lead ECG findings;
current, serious, clinically significant cardiac arrhythmias as determined by the Investigator.
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
Screening ECG abnormality documented by the investigator as medically significant
Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.
No clinically significant infections as judged by the treating investigator
Significant medical disease other than cancer
Significant medical disease other than cancer
Patients with significant intercurrent illnesses.
Any significant diseases (other than HL) or clinically significant findings, including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the subject from participating in the study
Clinically relevant serious co-morbid medical conditions.
Clinically significant systemic disease, as determined by the investigator, which could affect study participation or study results
Clinically significant anemia according to investigator's assessment due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
-  Participant has clinically significant uncontrolled condition(s) as described in the protocol.
Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.
Clinically significant surgery within 2 weeks of enrollment.
Significant gastrointestinal abnormality.
Clinically significant cardiac disease as per protocol-defined criteria.
History of clinically significant bleeding
Active clinically significant infection
Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.
Cardiac ejection fraction >= 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
Cardiac ejection fraction >= 40%, and no clinically significant electrocardiogram (ECG) findings.
Active clinically significant infection within 7-days of study treatment.
Electrocardiography (ECG) without evidence of clinically significant arrhythmia or ischemia.
Significant cardiovascular abnormalities as defined by any one of the following: a. congestive heart failure, b. clinically significant hypotension, c. symptoms of coronary artery disease, d. presence of cardiac arrhythmias on electrocardiography (EKG) requiring drug therapy, e. ejection fraction < 50 % (echocardiogram or multigated acquisition scan [MUGA]).
Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.
History or evidence of current clinically significant uncontrolled arrhythmias
Patients with history of clinically significant venous thromboembolism
Serum potassium, magnesium and calcium levels which fall within normal limits or levels outside the normal range determined not to be clinically significant by the principal investigator (PI)
Clinically significant toxicities from prior chemotherapy must not be greater than grade 1
Concurrent Illness\r\n* Patients with any clinically significant unrelated systemic illness (serious infections grade >= 2 or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results\r\n* Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient’s first malignancy has been in remission for at least 5 years from the end of treatment
Have clinically significant cardiac disease
Known, clinically significant carotid artery disease
Any clinically significant electrolyte imbalance, particularly hypokalemia and hypomagnesemia, should be corrected before treatment
Clinically significant malabsorption syndrome
Clinically significant hypersensitivity to denosumab or any components of denosumab 120 mg
Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
Any significant medical complications related to induction must have resolved
Subjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions
ARM B: Patients must not have clinically significant ascites and/or portal vein thrombosis
Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complications
Clinically significant gastrointestinal (GI) disorders, including history of small bowel obstruction unless the obstruction was a surgically treated remote episode
Uncontrolled and clinically significant disease-related metabolic disorder
Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal bleeding.
Clinically significant malabsorption syndrome
Patients must not have clinically significant autoimmune disease that requires treatment with immunosuppressant medications
Patients with a history of clinically significant venous thromboembolism will be excluded
Has a history of significant congestive heart failure or significant pulmonary disease
Other invasive cancers that are clinically active
Subjects with history of anaphylaxis or angioedema, bronchial asthma, peptic ulcer\n             and clinically significant food or drug allergy
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals
Absence of clinically significant cardiomyopathy, congestive heart failure
Any clinically significant active infection that requires systemic treatment at the time of enrollment
Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study - e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection
Absence of clinically significant cardiomyopathy, congestive heart failure
Has a clinically significant coagulopathy per investigator’s assessment
Patients on every 2, 3, or 4 week systemic treatment programs must be off the treatment program at least 2, 3, or 4 week, respectively, and must have recovered from any clinically significant toxicity experienced; patients on weekly or daily systemic treatment programs and patients receiving radiation must be off at least 1 week and must have recovered from any clinically significant toxicity experienced; must be at least 4 weeks and have recovered from major surgery
History or presence of clinically significant ventricular or atrial tachyarrhythmias, or cardiac arrest
Clinically significant resting bradycardia
Clinically significant systemic illness (e.g., serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the principal investigator (PI) would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complications; peripheral nerve symptoms from prior therapies or from tumor compression > grade 1
No clinically significant gastrointestinal bleeding within 24 weeks before the first dose of study treatment
Treatment for clinically-significant hyperglycemia, hyperlipidemia, or hypertension that develops on study is required
Sustained or clinically significant cardiac arrhythmias
Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the PI would likely compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complications
Clinically significant uncontrolled condition(s).
Clinically significant and unexplained elevated liver or renal function tests
Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
Patients with abnormal serum chemistry values, which in the opinion of the Investigator is considered to be clinically significant, will be excluded from the study
Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC).
Subject has active clinically significant GVHD or is on treatment with systemic corticosteroids for GVHD.
Subjects must not have clinically active cerebral metastases.
Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.
The participant has bowel obstruction or history of chronic diarrhea that is considered clinically significant.
Second primary malignancy that is clinically detectable or clinically significant at the time of consideration for study enrollment
Significant psychiatric or neurologic disorder which would compromise participation in the study
Clinically localized disease (?T2a) and
Any other clinically significant medical condition and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol.
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically significant cardiac arrhythmias
Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
Any sign of clinically significant bleeding
Clinically significant organ/system disease unrelated to RCC that in the judgment of the investigator should preclude treatment with dalantercept or axitinib.
Significant immunosuppression.
Patients must have a baseline electrocardiogram (ECG) performed within 42 days of registration that is normal or considered not clinically significant by the site investigator
Has clinically significant cardiac disease
Significant immunosuppression from:
Known clinically significant liver disease
Clinically significant gastrointestinal bleeding within 6 months prior to the first dose of ALRN-6924
Clinically significant third-space fluid accumulation
Urinalysis: No clinically significant abnormalities.
History of active clinically significant bleeding
Has a medical history of clinically significant lung disease
Clinically significant unrelated illness which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or be likely to interfere with the study procedures or results.
Clinically significant bleeding within 14 days of Cycle 1 Day 1 (Treatment Groups B and C only).
NYHA Class III or IV, uncontrolled hypertension, or clinically significant arrhythmia
History of clinically significant or uncontrolled cardiac, hepatic, or pulmonary disease
Clinically significant hemoptysis or tumor bleeding within two weeks prior to first dose of lenvatinib.
Clinically significant bleeding within 28 days of Cycle 1 Day 1
Clinically significant ascites
Clinically significant heart disease
Known clinically significant liver disease
ECG without evidence of clinically significant arrhythmia or ischemia.
Significant immunosuppression from:
Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ? Grade 1 per NCI CTCAE, Version 4.03 or are clinically stable and not clinically significant, at time of consent
Has a clinically significant gastrointestinal (GI) abnormality including:
significant fatigue
Evidence of clinically significant immunosuppression such as organ or stem cell transplantation, any severe congenital or acquired cellular and/or humoral immune deficiency, concurrent opportunistic infection.
Has clinically significant cardiac disease
No clinically significant progression outside of the CNS on most recent EGFR inhibitor therapy
Patients who have received treatment with clinically significant enzyme inducers within 14 days prior to registration are not eligible
ECG without evidence of clinically significant arrhythmia or ischemia
Significant immunosuppression from:
Clinically significant cardiac disease
Any prior or current clinically significant ascites
Patients must not have clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding
Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ? Grade 1 per CTCAE, version 4.03 or are clinically stable and not clinically significant, at time of enrollment
clinically significant symptomatic arrhythmia despite anti-arrhythmic therapy.
Significant serum chemistry abnormalities
Significant proteinuria at baseline (>= 500 mg/24 hours [h])
Clinically significant cardiac disease
Inclusion Criteria:\n\n        Adults (aged ? 18 years)\n\n        Histologically confirmed diagnosis of a B-cell lymphoma that has progressed in spite of\n        prior treatment, and for which additional effective standard therapy is not available\n\n        Eastern Cooperative Oncology Group (ECOG) performance status ? 2\n\n        Adequate hematological, renal, hepatic, and coagulation laboratory assessments\n\n        Must give written informed consent to participate in this study before the performance of\n        any study-related procedure\n\n        Exclusion Criteria:\n\n        A primary lymphoma of the central nervous system (CNS) or known lymphomatous involvement of\n        the CNS\n\n        Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the\n        absorption of CPI-1205, including any unresolved nausea, vomiting, or diarrhea that is\n        CTCAE grade >1\n\n        Treatment with proton pump inhibitors, H2 antagonists, or antacids\n\n        Achlorhydria, either documented or suspected on the basis of an associated disease (e.g.,\n        pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)\n\n        Impaired cardiac function or clinically significant cardiac diseases, including any of the\n        following:\n\n          -  Acute myocardial infarction or angina pectoris ? 6 months prior to starting study drug\n\n          -  New York Heart Association Class III or IV congestive heart failure\n\n          -  QTcF > 470 msec on the screening ECG\n\n        Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not\n        excluded)\n\n        A past medical history of other clinically significant cardiovascular disease (e.g.,\n        uncontrolled hypertension, history of labile hypertension or history of poor compliance\n        with an antihypertensive regimen)\n\n        Any other concurrent severe and/or uncontrolled concomitant medical condition that could\n        compromise participation in the study (e.g., clinically significant pulmonary disease,\n        clinically significant neurological disorder, active or uncontrolled infection)\n\n        Systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of\n        CPI 1205\n\n        Radioimmunotherapy (e.g., 131I-tositumomab, 90Y-ibritumomab tiuxetan) less than 6 weeks\n        before the first dose of CPI-1205\n\n        Treatment with an investigational small molecule less than 2 weeks before the first dose of\n        CPI-1205.\n\n        Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-1205.\n\n        Treatment with medications that are strong inhibitors of CYP3A4\n\n        Treatment with medications that are inducers of CYP3A4 enzymes\n\n        Treatment with medications that are known to carry a risk of Torsades de Pointes\n\n        Pregnant or lactating women\n\n        Women of child bearing potential and men with reproductive potential, if they are unwilling\n        to use adequate contraception while on study therapy and for 3 months thereafter\n\n        Patients unwilling or unable to comply with this study protocol
Clinically significant cardiac or pulmonary dysfunction
Have active, acute, or chronic clinically significant infections or bleeding within the last 6 months or previous thromboembolic or hemorrhagic events during anti angiogenic therapy.
Patient has no clinically significant abnormalities on urinalysis results.
Have a 12-lead Electrocardiogram (ECG) that is not clinically significant at screening, as determined by the investigator
Have ongoing clinically significant adverse event(s) due to prior treatments administered as determined by the investigator.
Subject with an unhealed surgical wound or other clinically significant wound
Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
Clinically significant, uncontrolled heart disease and/or recent cardiac repolarization abnormality including any of the following:
Clinically significant cardiac arrhythmias, complete left bundle branch block, high-grade AV block
Clinically significant hypercalcemia (including vomiting, dehydration and neurological symptoms)
Targeted prostate biopsy within 6 months prior to dosing, with a clinically significant lesion correlating with an mpMRI visible lesion.
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection, or any other condition that might compromise the participant's participation in the study.
Medically significant (symptomatic) bradycardia;
Clinically significant gastritis or peptic ulcer disease that would contraindicate the use of indomethacin.
Concurrent Illness Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.
Previous significant urinary obstructive symptoms
Other clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this trial
Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment
Abnormal ECGs that are clinically significant such as QT prolongation (QTc > 480 msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block or existing left bundle branch block, or signs of new, active ischemia.
Clinically significant pulmonary disease
Clinically significant gastrointestinal abnormalities
Active or clinically significant cardiac disease including:
Any other unstable or clinically significant concurrent medical condition
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
Patients with significant pulmonary dysfunction, large intracranial metastases, or significant thrombocytopenia (platelet count refractory to transfusion)
Subject with clinically significant wound
Have an acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator.
Serum bilirubin < 2 x upper limit of normal, or considered not clinically significant by the study doctor or designee
Patients with significant malabsorption as determined by the treating physician
Significant obstructive symptoms (IPSS greater than 20)
History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
Clinically significant or uncontrolled hypertension or cardiac disease
Known clinically significant hypotension
Known clinically significant autoimmune disorders requiring on-going systemic immune-suppression for control
Have blood urea nitrogen and serum creatinine (BUN/Cr) without clinically significant abnormalities after review by the study physicians
Complete blood count (CBC) without clinically significant abnormalities after review by the study physicians
Have altered immunity such as autoimmune disorders, clinically significant anemia, hemophilia, and blood dyscrasias
Any ongoing acute clinically significant toxic effect of prior anticancer therapy or any persisting complication of prior surgery.
Have clinically significant cardiac disease
Clinically significant psychiatric disease which, in the opinion of the PI or sub-investigator (I), would render immunotherapy and its potential sequelae unsafe or compliance with procedural requirements unlikely
Patients with clinically significant dermatological disorders, e.g., eczema or psoriasis, as judged by the principal investigator, or any unhealed skin wounds or ulcers
History of clinically significant cardiac or pulmonary dysfunction
Another malignancy that is clinically significant or requires active intervention (chemotherapy or radiation)
No clinically significant infections as judged by the treating investigator.
Patients with any clinically significant systemic illness, including serious infection, pulmonary, hepatic, or other organ impairment, that would compromise tolerance and/or timely completion of protocol therapy
Active, clinically significant Electrocardiogram (ECG) abnormalities
Evidence of severe or uncontrolled systemic diseases (example, unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes).
Uncontrolled clinically significant pulmonary disease.
Clinically significant cardiovascular disease (e.g., uncontrolled or any NYHA Class 3 or 4 CHF, uncontrolled angina, history of MI, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
Clinically significant, uncontrolled heart disease and/or recent cardiac event within 6 months prior to study
Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
Subject has clinically significant coagulation abnormality unless secondary to AML.
Cardiac ejection fraction ? 50% and no clinically significant ECG findings
History of clinically-significant cardiovascular disease; gastrointestinal perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4 weeks of first study drug administration
History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or drug intake
No clinically significant cardiac conduction disorder on screening.
Significant cardiovascular abnormalities as defined by any one of the following:\r\n* Congestive heart failure\r\n* Clinically significant hypotension\r\n* Symptoms of coronary artery disease (angina, dyspnea)\r\n* Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy
History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
Subject has a clinically significant coagulation disorder or disease, defined as a platelet count < 100,000 per microliter or International Normalized Ratio > 1.5 within 4 weeks of surgery;
Potassium and calcium (corrected for albumin), within normal limits for the institution, or =< grade 1 if judged not clinically significant by the investigator
Participant has persistent diarrhea or clinically significant malabsorption syndrome or known sub-acute bowel obstruction ? Grade 2, despite medical management
Significant comorbidity (cirrhosis, severe coronary artery disease, significant psychiatric illness, or other that may compromise the ability to safely administer the therapy at the discretion of the primary investigator)
Clinically significant uncontrolled condition(s)
Clinically significant persistent immune-related adverse events following prior therapy.
Patients with any clinically significant unrelated systemic illness (e.g., serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient’s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.
Clinically active cerebral metastases.
Subjects with a history of intestinal perforation, colitis, clinically significant gastrointestinal bleeding or intestinal obstruction within one year prior to enrollment.
Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol including:\r\n* History of myocardial infarction in the past year or unstable, severe cardiovascular disease including angina or congestive heart failure (CHF) with symptoms at rest, or clinically significant abnormalities on the electrocardiogram (ECG)\r\n* Clinically significant and/or unstable pulmonary, gastrointestinal, hepatic, or renal disease\r\n* Insulin-requiring diabetes or uncontrolled diabetes mellitus,\r\n* Uncontrolled hypertension (systolic blood pressure [BP] > 170 or diastolic blood pressure [BP] > 100)
Clinically significant peripheral artery disease (e.g., claudication with < 1 block) or any other arterial thrombotic event
Have current or prior history of infection or clinically significant adverse events (AEs) associated with an exogenous implant(s) or device(s) that cannot be easily removed
Clinically significant valvular heart disease
Presence of clinically significant ascites
Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy
Patients with clinically significant cardiomyopathy requiring treatment
History or evidence of current, clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to the initiation of therapy on this protocol are eligible)
Participants with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complications
History of clinically significant or uncontrolled cardiac disease.
Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy.
Known history of ischemic cardiac disease (including angina requiring anti-anginal medications, myocardial infarction, coronary artery disease documented on cardiac catheterization or ischemia documented on stress test), congestive heart failure, clinically significant arrhythmia or conduction system abnormalities, clinically significant valvular disease, clinically significant pericardial effusion or EF below the lower limit of normal
Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
History of clinically significant (as determined by the treating physician) atrial arrhythmia
Concurrent disease or condition that would interfere with study participation or safety, such as:\r\n* Active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade > 2 by NCI CTCAE (v 4.03) within 14 days prior to enrollment\r\n* Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders\r\n* Non-healing wound, ulcer, or bone fracture\r\n* Bone marrow disorder including myelodysplasia
Clinically significant abnormality on electrocardiogram (ECG)
PHASE I: Clinically significant malabsorption syndrome
Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C), if deemed clinically significant by the treating physician.
No arrhythmia interpreted by the study cardiologist to be clinically significant
History of clinically significant gastrointestinal (GI) bleeding within prior 2 months prior to enrollment
No clinically significant infections as judged by the treating physician.
Patients with psychiatric disability judged by the investigator to be clinically significant so as to preclude informed consent or compliance with drug intake
Significant comorbidity: Patients with clinically significant and uncontrolled major disease or disorder that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit study compliance.
Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to first dose of lenvatinib
Clinically significant conditions that increase the risk for antiangiogenic therapy.
Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug; clinically significant metabolic enzyme inducers are not permitted during this study
PART B: History of clinically significant bleeding disorder
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection
Evidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema, vomiting and nausea, or reduced level of consciousness)
History of previous clinically significant GI bleed in the last 6 months prior to first dose
History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake
History of clinically significant bleeding episodes
Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia
Active infection or antibiotics within 48 hours prior to study enrollment, including unexplained fever (temp > 38.1°C) if deemed clinically significant by the treating physician.
Clinically significant acute pancreatitis within 12 weeks of treatment with protocol therapy as indicated by the presence of two of the three following criteria: abdominal pain in the epigastrium, often with radiation to the back, serum amylase and/or lipase greater than three times the upper limit of normal, and/or characteristic findings (peripancreatic inflammation, fat necrosis, etc.) from abdominal imaging; clinically significant will be defined as that requiring oral narcotics or hospital admission
Clinically significant cardiac disease as defined in the protocol
For patients with history of major coronary artery disease in the judgment of the responsible physician, a cardiac stress test (either exercise or pharmacologic) that demonstrates clinically significant abnormalities when performed within 4 weeks of first dose of study drug
>= grade 1 proteinuria at baseline or clinically significant impairment of renal function
Clinically significant cardiac disease
Any >grade 1 persistent clinically significant toxicities from prior chemotherapy.
Documented or known clinically significant bleeding disorder.
History of or presence of clinically significant ventricular or atrial tachyarrhythmias
Clinically significant resting bradycardia
Clinically significant cardiovascular disease or cardiac insufficiency,cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrolment, angina pectoris within 3 months of enrolment.
Unstable coronary disease or clinically significant electrocardiogram (ECG) (12-lead) abnormalities, as determined by the investigator
History of clinically significant bleeding within 6 months of enrollment/randomization
Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results
Patients with a history of clinically significant cutaneous drug reaction to minocycline, as documented in the patient medical records
History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake
No significant immunodeficiency
Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
The patient has LVEF ?40% by ECHO or MUGA scan and no clinically significant abnormalities in 12-lead ECG
Subjects with a clinically significant or unstable medical condition that would preclude safe and complete study participation
History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake
Clinically significant resting brachycardia (< 50 beats per minute)
History of or presence of clinically significant ventricular or atrial tachyarrhythmias
Adequate cardiac function defined as no clinically significant history of arrhythmia as determined by the principal investigator (PI) and/or the treating physician, history of myocardial infarction (MI) or clinically significant abnormal electrocardiogram (EKG), as determined by the PI and/or the treating physician, within 3 months prior to study enrollment; cardiac function will be assessed by history and physical examination
Clinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment principal investigator (PI) or associated investigator (AI) would render the patient unlikely to tolerate the protocol therapy or complete the study
Clinically significant valvular heart disease
Significant co-morbidity indicated by major organ system dysfunction
Presence of clinically relevant ascitis
Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
Subject has a clinically significant peripheral artery disease, e.g., those with claudication, within 6 months
Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
Clinically significant cardiovascular disease defined as: i. Left ventricular ejection fraction (LVEF) ? 50%, measured within 3 months prior to Day 1 confirmed by ECHO/MUGA ii. Congestive heart failure requiring medical therapy iii. Chronic stable angina requiring medical therapy iv. Prior cerebrovascular accident with sequelae c. Clinically significant pulmonary disease defined as: i. Forced expiratory volume in 1 second (FEV1) ? 65% of expected ii. Lung diffusing capacity for carbon monoxide (DLCO) ? 65% of expected Confirmed by pulmonary tests. d. Diabetes mellitus with symptomatic end-organ damage (e.g., retinopathy, nephropathy, neuropathy, vasculopathy) e. Autoimmune inflammatory conditions (e.g., rheumatoid arthritis, systemic lupus erythematous, inflammatory bowel disease, or similar) requiring chronic disease modifying therapy (e.g., etanercept, adalimumab, infliximab, rituximab, methotrexate, or similar) f. Class III obesity defined as a Body Mass Index (BMI) > 40 kg/m2 g. Renal impairment defined as serum creatinine > 1.3 mg/dL (> 115 µmol/L) or creatinine clearance <70 ml/min h. Clinically significant cognitive impairment defined as requiring medical therapy and/or assistance with activities of daily living
Known clinically significant liver disease
Concurrent, clinically significant, active malignancies within two years of study enrollment.
Resting ECG with clinically significant abnormal findings;
History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating (eg, active or clinically significant history of disease involving a major organ system—vascular, cardiac, pulmonary, hepatic, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine or immunodeficiency, autoimmune or clinically significant active psychiatric disorders)
Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
Patients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
Clinically significant cardiac disease
History of significant cerebrovascular disease or event with significant symptoms
Patients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
Other clinically significant co-morbidities
Central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant to preclude informed consent or interfere with complying with protocol treatments
Patients with clinically significant co-morbid conditions, including, but not limited to: hypotension, chronic interstitial lung disease, uncontrolled diabetes
Significant gastrointestinal disorder with diarrhea as major symptom
Clinically significant hearing loss or ringing in the ears
Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal or Associate Investigator would compromise the patient’s ability to tolerate PEG-Intron or are likely to interfere with the study procedures or results
Uncontrolled clinically significant arrhythmias
Has clinically significant heart disease that affects normal activities
Significant ECG abnormalities.
Significant screening electrocardiogram (ECG) abnormalities;
All clinically significant toxicities from prior chemotherapy must be ? Grade 1.
History of clinically significant heart problems
Clinically significant glaucoma, retinitis pigmentosa, or macular degeneration.
Adequate recovery in the investigators opinion from any clinically significant toxicity from prior therapy
Clinically significant electrolyte imbalance ? Grade 2.
Evidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
Has any clinically significant co-morbidities.
History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
History of clinically significant cardiac disease
Subject has no clinically significant abnormalities in urinalysis results (obtained ? 14 days prior to starting Cycle 1 Day 1).
Ongoing or clinically significant active infection as judged by the investigator.
Ongoing or clinically significant active infection as judged by the investigator.
Clinically significant ECG changes
Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding
Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality
Subject has an active, uncontrolled systemic infection considered opportunistic, life-threatening, or clinically significant at the time of treatment.
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient’s ability to tolerate protocol therapy or would likely interfere with the study procedures or results
Patients with clinically significant severe cardiorespiratory disease.
Patients with clinically significant ophthalmologic findings (as determined by an ophthalmologist) during screening should be excluded from the trial
Clinically significant systemic illness (e.g. serious active infections or significant vital other organ dysfunction), that in the judgment of the principal investigator (PI) would likely compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk of complications
Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
Clinically significant, uncontrolled heart disease and/or recent cardiac events.
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or results
NON-PROGRESSED DIPG (STRATUM 2): Patients have any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the ability of the patient to tolerate protocol therapy or put them at additional risk for toxicity or would interfere with the study procedures or results
Has a medical history of clinically significant lung diseases
Clinically significant electrolyte imbalance ? grade 2.
Clinically significant cardiac disease
History of clinically significant hypercalcemia
Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
Clinically significant ascites or clinical evidence or history of portosystemic hypertension or cirrhosis.
Active and clinically significant systemic or localized infection.
Any sign of clinically significant bleeding
Significant organ dysfunction.
Within normal limit hematopoietic capacity, hepatic and renal function; values outside those limits may be allowed at the digression of the principle investigator (PI), if they are determined as not clinically significant
History of clinically significant cardiac dysfunction
Current diagnosis of any other active or clinically significant non-breast cancer
Abnormal 12-lead electrocardiogram (ECG) judged to be clinically significant by the Investigator;
History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake
Clinically significant ascites
Other current, severe, uncontrolled systemic disease (e.g., clinically significant\n             metabolic disease, wound healing disorders, ulcers)
Clinically significant bleeding within 30 days before enrollment
Clinically significant cardiac disease, including:
Known clinically significant liver disease
Clinically significant co-morbidities
Have clinically significant cardiac disease
Normal electro cardio gram (ECG) or ECG with no clinically significant findings;
Subject with electrocardiogram (ECG) abnormalities on a 12-lead ECG performed within 14 days before start of the study drug that are considered by the Investigator to be clinically significant.
Clinically significant bleeding within 28 days of study Day 1
Clinically significant hypotension
Clinically significant autoimmune disorders requiring on-going systemic immune-suppression for control
Any clinically significant and uncontrolled major medical condition
Subjects with clinically significant ascites
Clinically significant cardiac disease
Patient has a urinalysis obtained (=< 14 days prior to randomization) and the results are deemed not clinically significant by the investigator
Any clinically significant cardiac disease defined as NYHA class III or IV.
ECG with no clinically significant findings;
Clinically significant central nervous system disease defined as untreated, progressive, or requiring steroids for control of symptoms.
A history or evidence of current clinically significant uncontrolled arrhythmias;
Uncontrolled systemic disease (e.g., clinically significant cardiac, pulmonary or metabolic disease)
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. The Medical Monitor should be contacted for any uncertainties.
Clinically significant pulmonary, endocrine, neurologic, hematologic, gastrointestinal (GI), autoimmune, psychiatric or genitourinary disease unrelated to HCC that in the judgment of the investigator should preclude treatment with dalantercept or sorafenib.
Clinically significant active pulmonary risk
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or anti-fungals.
History of or evidence of clinically significant uncontrolled cardiac arrhythmias
Urinalysis: No clinically significant abnormalities
Clinically significant gastrointestinal (GI) bleeding within 6 months prior to Cycle 1, Day 1
Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug.
History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias
Significant symptomatic deterioration of lung function.
Clinically significant and uncontrolled major medical condition(s) including but not limited to:
Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:\r\n* Active systemic fungal infection\r\n* Diagnosis of fever and neutropenia within 1 week prior to study drug administration
Clinically significant resting bradycardia
Any other clinically significant heart disease
A history or evidence of current clinically significant uncontrolled arrhythmias (exception: subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible)
Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug
Clinically significant gastrointestinal bleeding occurring <= 4 weeks prior to randomization
Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
Clinically significant anemia unrelated to MDS
No evidence of a clinically significant active infection
No evidence of clinically significant congestive heart failure, (ejection fraction of 45% or greater)
Clinically significant toxicities from prior chemotherapy must be resolved to Grade ?
History of clinically significant psychiatric illness that would prevent the patient from providing a valid ICF and complying with protocol requirements
Clinically significant gastrointestinal abnormalities, apart from gastric cancer, including uncontrolled inflammatory gastrointestinal diseases
Clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders
History of clinically significant cardiac disease.
The subject has experienced any of the following within 3 months before the first dose of study treatment:\r\n* Clinically-significant hematemesis or gastrointestinal bleeding\r\n* Clinically-significant hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood\r\n* Any other signs indicative of pulmonary hemorrhage
Clinically significant abnormalities of glucose metabolism.
Clinically-significant thrombosis within 3 months of screening
Participants who have not recovered from clinically significant adverse effect(s)/toxicity(s) of the previous therapy.
Second primary malignancy that is clinically detectable or clinically significant at the time of consideration for study enrollment
Significant psychiatric or neurologic disorder which would compromise participation in the study
History of clinically significant bleeding within 6 months of enrollment/randomization
History of significant cerebrovascular disease or event with significant symptoms or sequelae.*
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient’s ability to tolerate protocol therapy or would likely interfere with the study procedures or results
Lifetime history of suicidality, homicidality, or clinically significant hostility/aggression
Clinically significant gastro-intestinal disease, including uncontrolled inflammatory gastro-intestinal diseases
Clinically significant cardiac disease;
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system (CNS) disease, active infection, or any other condition that could compromise the subject's participation in the study
Clinically significant cardiac or pulmonary dysfunction
Clinically significant history of liver disease
Has a significant clinical disease or condition
Significant renal impairment as determined per investigator discretion
Clinically significant resting bradycardia
Other clinically significant heart disease
History of severe cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator, will interfere with the safety of the individual subject.
Persistent clinically significant toxicities from prior chemo ? Grd 1
Persistent clinically significant toxicities from prior chemo ? Grd 1
Persistent clinically significant toxicities from prior chemo ? Grd 1 or Grd 2 neuropathy without pain
Persistent clinically significant toxicities from prior chemo ? Grd 1, or Grd 2 neuropathy without pain.
History of any clinically significant local or systemic infectious disease within 4 weeks prior to initial treatment administration
No clinically significant infections as judged by the treating investigator.
A history of clinically significant disease that places subject at an unacceptable risk for study entry
Clinically significant untreated system illness, such as seriously infections, autoimmunity or organ dysfunction, which in the judgement of the Principal or Associate Investigators would compromise the patient’s ability to tolerate the investigational agents or are likely to interfere with the study procedures or results
Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgement of the Principal or Associate Investigators would compromise the patient’s ability to tolerate the investigational agents or are likely to interfere with the study procedures or results
Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient’s ability to tolerate the investigational agents or are likely to interfere with the study procedures or results
History of clinically significant haemoptysis within the past 3 months
Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
Clinically significant encephalopathy
History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia
Clinically significant obstructive airway disease
Subjects must be free of any clinically significant disease other than cancer that would interfere with the study evaluations
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically significant cardiac arrhythmias
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient’s participation in the study
Any clinically significant electrolyte imbalance, particularly hypokalemia and hypomagnesemia, should be corrected before treatment
No specific organ function parameters are required; however, significant abnormalities should be discussed with the study PI (this is especially the case for significant renal dysfunction)
Subjects must be free of any clinically significant disease other than cancer that would interfere with the study evaluations
Serum bilirubin < 2 x ULN, or considered not clinically significant by the study doctor or designee
Known clinically significant autoimmune disorders requiring systemic immunosuppression for control
History of clinically significant cardiac or pulmonary dysfunction
No active untreated clinically significant psychiatric condition (psychosis, bipolar disorder, or depression)
Patient has clinically active diverticular disease
Significant psychiatric history
Sustained or clinically significant cardiac arrhythmias
Patients with clinically significant illnesses which, according to the Investigator, could compromise participation in the study;
Patient has had no clinically significant change in renal status within 3 months prior to screening, according to Investigator's review of clinical patient records.
Uncontrolled clinically significant arrhythmia in last 6 months.
Any clinically significant comorbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease (specified below), active CNS disease, active infection, or any other condition that could compromise the participant's participation in the study.
Abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that, in the opinion of the investigator, are considered to be clinically significant.
Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
Clinically significant cardiac disease
Significant cognitive impairment
Married or cohabiting with a significant other of either gender for more than one year
A significant anxiety disorder
Patients with irritable bowel syndrome, Crohn's disease, or other clinically significant gastrointestinal (GI) related condition that might confound the VEGF-TKI-related-diarrhea endpoint
Manometry felt to be clinically indicated
Subjects with clinically significant uncontrolled cardiac disease
Report a clinically significant level of FCR (as assessed with the Fear of Cancer Recurrence Inventory Short Form >= 13)
Free from significant psychiatric history
Recent or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, bleeding, inflammation, emesis, diarrhea > grade 1)
Concurrent clinically significant infections as determined by the treating investigator.
Clinically significant pulmonary compromise (e.g. require supplemental oxygen)
Clinically significant cardiac or pulmonary disease
Clinically significant uncontrolled condition(s).
Clinically significant gastrointestinal disorder
Any clinically significant Grade ?3 immune-related adverse event (irAE)
Clinically significant comorbid medical conditions or lab abnormalities
History of clinically significant coagulation or platelet disorder in the past 12 months
Evidence of GVHD at the time of enrollment as assessed clinically
Symptomatic tachycardia and uncontrolled hypertension (determined to be clinically significant by the PI)
Symptomatic tachycardia and uncontrolled hypertension (determined to be clinically significant by the PI)
Intermediate phase lymphedema; defined clinically as significant persistent pitting edema on physical exam
History of or current clinically significant immunodeficiency
History of or current clinically significant alloimmunization to leukocyte antigens
Impaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* Corrected QT (QTc) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor adherence with an antihypertensive regimen)
Patient has acute bleeding that is clinically significant within 24 hours before the start of study treatment.
Clinically significant elevation of liver function tests prior to the first day of dosing (FDD) that at the discretion of the treating physician would preclude the administration of an azole antifungal
Aspartate transaminase (AST), alanine transferase (ALT) within institutional limits of normal or judged to be not clinically significant by the investigator
Blood urea nitrogen (BUN) within institutional limits of normal or judged to be not clinically significant by the investigator
Patients must not have had a clinically significant cardiac event within 6 months before entry; or the presence of any other uncontrolled cardiovascular conditions that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
Clinically significant bacteremia or fungemia
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal dysfunction, which in the opinion of the investigator precludes administration of the study vaccine
Presence of clinically significant infections or congenital or acquired immunodeficiency
sustained clinically-significant worsening (investigator's assessment) from baseline granulocyte, platelet, or hemoglobin values (? 2 values, separated by ? 2 weeks)
Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.
Subject has significant auto-immune disease
Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
Unstable or clinically significant concurrent medical condition
Clinically significant edema requiring diuretic therapy
Clinically cancer-free (no evidence of disease)
Complete blood count (CBC) including diff & platelets - without clinically significant abnormalities
Clinically significant abnormalities on electrocardiogram (ECG) at screening.
Have BUN/Cr (Blood urea nitrogen and serum creatinine) without clinically significant abnormalities after review by the study physicians
Liver enzymes without clinically significant abnormalities after review by the study physicians
CBC (complete blood count) without clinically significant abnormalities after review by the study physicians
HEALTHY VOLUNTEER: Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder within the last 5 years; subjects who have had situational depression may be enrolled in the study at the discretion of the investigator
Significant valvular disease, or significant pulmonary disease requiring supplemental oxygen therapy
Has clinically significant corneal disease
History of clinically significant or uncontrolled cardiac disease.
Cardiac ejection fraction ? 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings
Clinically significant cardiac disease within last 12 months
History of clinically significant or active cardiac disease
Active clinically significant infection
Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ? Grade 1 by C1D1.
Patients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
Clinically significant gastrointestinal malabsorption syndrome
Significant ophthalmologic abnormality,
Patients with clinically significant and unstable renal and/or liver disease (eg, transplant recipients in rejection)
Congestive heart failure, clinically significant
Determined by investigator to be clinically unsuitable for the study
Clinically severe cardiovascular disease or clinically significant electrocardiogram (ECG) abnormality.
Uncontrolled, clinically significant pulmonary disease.
History of clinically significant congestive heart failure
no evidence of active/clinically significant bleeding. May be evidence of punctate hemorrhage w/in tumor as long as not considered clinically significant to warrant urgent surgical evacuation
Evidence of clinically significant immunosuppression
History of or presence of clinically significant ventricular or atrial tachyarrhythmias
Clinically significant resting bradycardia
Concomitant use or administration of clinically significant enzyme inducers less than or equal to (<=) 14 days before the first dose of TAK-580.
Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months
Clinically significant abnormalities on electrocardiogram (ECG)
History of clinically significant cardiac dysfunction
Clinically significant active infection
Current or prior history of myelodysplastic syndrome, leukemia or clinically significant (as per Investigator judgment) bone marrow failure.
Any clinically significant comorbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease (specified below), active central nervous system disease, active infection, or any other condition that could compromise the participant's participation in the study. Participants with any of the following cardiovascular conditions are excluded:
Abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant.
Evidence of clinically significant immunosuppression
is clinically unstable and/or
Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis (Parts D and E only).