Subject or subject's partner is willing to use condoms for  months after receiving Toca  or until there is no evidence of the virus in his/her blood, whichever is longer.
Subjects who have any other disease, either metabolic or psychological, which as per Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications
The subject may have had other systemic chemotherapy for PCNSL during the  days since PCNSL diagnosis; prior systemic chemotherapy must have been given at least  weeks prior to study entry ( weeks for nitrosourea agents), with the exceptions of methotrexate and rituximab which may have been given at least  days prior; ocular lymphoma treatment may have been given any time prior to study entry; if the subject has undergone treatment for parenchymal disease and the parenchymal disease has progressed on a stable or increasing dose of steroids, the subject is not eligible for enrollment
SCCHN: Subject must have a locally confirmed diagnosis of SCCHN. Subject must have received at least  prior approved agent for advanced or metastatic disease followed by documented progressive disease.
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          . Subject is ? years of age at the time of signing the informed consent form (ICF)\n\n          . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted\n\n          . Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements\n\n          . Subjects must have a documented diagnosis of Multiple myeloma (MM) and have measurable\n             disease by serum and/or urine protein electrophoresis (sPEP or uPEP): sPEP ?. g/dL\n             or uPEP\n\n             ? mg/ hours\n\n          . All subjects must have received at least  prior myeloma regimens (note: induction\n             with or without bone marrow transplant and with or without maintenance therapy is\n             considered one regimen)\n\n          . All subjects must have received prior treatment with at least  consecutive cycles of\n             a lenalidomide or pomalidomide-containing regimen\n\n          . All subjects must have received prior treatment with at least  consecutive cycles of\n             a proteasome inhibitor or a proteasome inhibitor-containing regimen\n\n          . For Part  (Cohort C and Cohort D), all subjects must have received prior treatment\n             with at least  consecutive cycles of an anti-CD therapy or an anti-CD-containing\n             regimen\n\n          . All subjects must have documented disease progression on or within  days from the\n             last dose of their last myeloma therapy\n\n         . Eastern Cooperative Oncology Group (ECOG) performance status score of ,  or \n\n         . A female of childbearing potential (FCBP) is a female who: ) has achieved menarche at\n             some point, ) has not undergone a hysterectomy or bilateral oophorectomy, or ) has\n             not been naturally postmenopausal (amenorrhea following cancer therapy does not rule\n             out childbearing potential) for at least  consecutive months (ie, has not had menses\n             at any time in the preceding  consecutive months) and must:\n\n               . Have two negative pregnancy tests as verified by the Investigator prior to\n                  starting study therapy. She must agree to ongoing pregnancy testing during the\n                  course of the study, and after end of study therapy. This applies even if the\n                  subject practices true abstinence* from heterosexual contact.\n\n               . Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed on a monthly basis and source documented) or agree to use, and be able\n                  to comply with two forms of contraception: one highly effective, and one\n                  additional effective (barrier) measure of contraception without interruption \n                  days prior to starting investigational product, during the study therapy\n                  (including dose interruptions), and for  days after discontinuation of study\n                  therapy. Contraception requirements are detailed in Appendix D.\n\n         . Male subjects must:\n\n             a. Practice true abstinence* (which must be reviewed on a monthly basis and source\n             documented) or agree to use a condom during sexual contact with a pregnant female or a\n             female of childbearing potential while participating in the study, during dose\n             interruptions and for at least  days following the last dose of CC-, even if he\n             has undergone a successful vasectomy.\n\n             * True abstinence is acceptable when this is in line with the preferred and usual\n             lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation,\n             symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of\n             contraception.]\n\n         . Males must agree to refrain from donating sperm while on CC-, during dose\n             interruptions and for at least  days following last dose of CC-.\n\n         . All subjects must agree to refrain from donating blood while on CC-, during dose\n             interruptions and for at least  days following the last dose of CC-.\n\n         . All male and female subjects must follow all requirements defined in the Pregnancy\n             Prevention Program (v.).\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          . Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study\n\n          . Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study\n\n          . Subject has any condition that confounds the ability to interpret data from the study\n\n          . Subject has nonsecretory or oligosecretory multiple myeloma\n\n          . Subjects with Plasma Cell leukemia\n\n          . Any of the following laboratory abnormalities\n\n               -  Absolute neutrophil count (ANC) <,/?L\n\n               -  Platelet count <,/?L Corrected serum calcium >. mg/dL (>. mmol/L)\n\n               -  Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)\n                  or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ?.\n                  x upper limit of normal (ULN)\n\n               -  Serum total bilirubin and alkaline phosphatase >. x Upper Limit of Normal (ULN)\n\n               -  Subjects with serious renal impairment (-hour creatinine clearance [CrCl] <\n                  mL/min) or requiring dialysis would be excluded\n\n          . Subjects with peripheral neuropathy ?Grade \n\n          . Subjects with gastrointestinal disease that may significantly alter the absorption of\n             CC-\n\n          . Subjects with a prior history of malignancies, other than MM, unless the subject has\n             been free of the disease for ? years with the exception of the following noninvasive\n             malignancies:\n\n               -  Basal cell carcinoma of the skin\n\n               -  Squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histological findings of prostate cancer such as Ta or Tb using the\n                  Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer\n                  that is curative\n\n         . Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide,\n             pomalidomide or DEX\n\n         . Subject has known or suspected hypersensitivity to the excipients contained in the\n             formulation of CC- or DEX\n\n         . Subject has received any of the following within the last  days of initiating IP:\n\n               -  Plasmapheresis\n\n               -  Major surgery (as defined by the Investigator)\n\n               -  Radiation therapy other than local therapy for MM associated bone lesions\n\n               -  Use of any systemic myeloma drug therapy\n\n         . Subject has been treated with an investigational agent (ie, an agent not commercially\n             available) within  days or  half-lives (whichever is longer) of initiating\n             investigational product (IP)\n\n         . Subject has any one of the following:\n\n               -  Clinically significant abnormal electrocardiogram (ECG) finding at Screening\n\n               -  Congestive heart failure (New York Heart Association Class III or IV)\n\n               -  Myocardial infarction within  months prior to starting IP\n\n               -  Unstable or poorly controlled angina pectoris, including the Prinzmetal variant\n                  of angina pectoris\n\n         . Subject has current or prior use of immunosuppressive medication within  days prior\n             to the first dose of IP. The following are exceptions to this criterion:\n\n               -  Intranasal, inhaled, topical or local steroid injections (eg, intra-articular\n                  injection)\n\n               -  Systemic corticosteroids at physiologic doses that do not exceed  mg/day of\n                  prednisone or equivalent\n\n               -  Steroids as premedication for hypersensitivity reactions (eg, computed tomography\n                  [CT] scan premedication)\n\n         . Subject has taken a strong inhibitor or inducer of CYPA/ including grapefruit, St.\n             John's Wort or related products within two weeks prior to dosing and during the course\n             of study\n\n         . Subject known to test positive for human immunodeficiency virus (HIV), chronic or\n             active hepatitis B, or active hepatitis A or C\n\n         . Subject is unable or unwilling to undergo protocol required thromboembolism\n             prophylaxis\n\n         . Subject is a female who is pregnant, nursing or breastfeeding
Two appropriate CB units identified for the subject.
Inclusion Criteria:\n\n          -  Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no\n             limit to the number of prior treatment regimens) that is confirmed by available\n             pathology records or current biopsy as well as:\n\n               -  Subject in the escalation cohort has received all standard therapies (unless the\n                  therapy is contraindicated or intolerable) felt to provide clinical benefit for\n                  the subject's specific tumor type. OR\n\n               -  Subject in an expansion cohort has received at least one standard therapy for the\n                  subject's specific tumor type.\n\n          -  For Korea only: Subject has locally-advanced (unresectable) or metastatic solid tumor\n             malignancy (no limit to the number of prior treatment regimens) that is confirmed by\n             available pathology records or current biopsy and has received all standard therapies\n             (unless the therapy is contraindicated or intolerable) felt to provide clinical\n             benefit for the subject's specific tumor type.\n\n          -  Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ,  or\n             .\n\n          -  Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was\n             at least  days prior to initiation of study drug administration. A subject with\n             epidermal growth factor receptor (EGFR) mutation-positive NSCLC is allowed to remain\n             on EGFR tyrosine kinase inhibitor (TKI) therapy until  days prior to the start of\n             study drug administration.\n\n          -  For Korea only: Subject's last dose of prior antineoplastic therapy, including any\n             immunotherapy, was at least  days prior to initiation of study drug administration.\n             For drugs with a half-life greater than or equal to  days, the investigator should\n             consider if this washout is sufficient. A subject with epidermal growth factor\n             receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is allowed to\n             remain on EGFR tyrosine kinase inhibitor (TKI) therapy until  days prior to the start\n             of study drug administration.\n\n          -  Subject has completed any radiotherapy (including stereotactic radiosurgery) at least\n              weeks prior to study drug administration.\n\n          -  Subject's adverse events (excluding alopecia) from prior therapy have improved to\n             grade  or baseline within  days prior to start of study treatment.\n\n          -  Subject with metastatic castration resistant prostate cancer (mCRPC) (positive bone\n             scan and/or soft tissue disease documented by computed tomography (CT) / magnetic\n             resonance imaging (MRI)) meets both of the following:\n\n               -  Subject has serum testosterone ?  ng/dL at screening.\n\n               -  Subject has had an orchiectomy or plans to continue androgen deprivation therapy\n                  (ADT) for the duration of study treatment.\n\n          -  Subject has adequate organ function prior to start of study treatment as indicated by\n             the following laboratory values. If a subject has received a recent blood transfusion,\n             the laboratory tests must be obtained ?  weeks after any blood transfusion.\n\n          -  Female subject must either:\n\n               -  Be of non-childbearing potential: Postmenopausal (defined as at least  year\n                  without any menses for which there is no other obvious pathological or\n                  physiological cause) prior to screening, or documented surgically sterile (e.g.,\n                  hysterectomy, bilateral salpingectomy, bilateral oophorectomy).\n\n               -  Or, if of childbearing potential, agree not to try to become pregnant during the\n                  study treatment and for  months after the final study drug administration, and\n                  have a negative urine or serum pregnancy test prior to study drug administration,\n                  and, if heterosexually active, agree to consistently use one form of highly\n                  effective birth control starting at screening and throughout the study treatment\n                  and  months after the final study drug administration.\n\n          -  Female subject must agree not to breastfeed starting at screening and throughout the\n             study treatment, and for  months after the final study drug administration.\n\n          -  Female subject must not donate ova starting at screening and throughout the study\n             treatment, and for  months after the final study drug administration.\n\n          -  A sexually active male subject with female partner(s) who are of childbearing\n             potential is eligible if:\n\n               -  Agree to use a male condom starting at screening and continue throughout the\n                  study treatment, and for  months after the final study drug administration.\n\n               -  If the male subject has not had a vasectomy or is not sterile as defined below\n                  the subject female partner(s) is utilizing one form of highly effective birth\n                  control starting at screening and continue throughout the study treatment and for\n                   months after the final study drug administration.\n\n          -  Male subject must not donate sperm starting at screening and throughout the study\n             treatment, and for  months after the final study drug administration.\n\n          -  Male subject with a pregnant or breastfeeding partner(s) must agree to remain\n             abstinent or use a condom for the duration of the pregnancy or time partner is\n             breastfeeding throughout the study treatment and for  months after the final study\n             drug administration.\n\n          -  Subject agrees not to participate in another interventional study while receiving\n             study drug (subjects who are currently in the follow-up period of an interventional\n             clinical trial are allowed).\n\n        Additional Inclusion Criteria for Subjects in the Expansion Cohorts:\n\n          -  Subject meets one of the following:\n\n               -  Subject has the tumor type for which a confirmed response was observed in a\n                  monotherapy or combination therapy dose escalation cohort; or\n\n               -  For an expansion cohort opened due to achieving predicted efficacious exposure,\n                  subject has squamous cell carcinoma of the head and neck (SCCHN).\n\n          -  Subject has at least  measureable lesion per Response Evaluation Criteria in Solid\n             Tumors (RECIST) .. The measureable lesion must be outside the field of radiation if\n             subject had prior radiotherapy. Subjects with mCRPC who do not have measurable lesions\n             must have at least one of the following:\n\n               -  Progression with  or more new bone lesions; or\n\n               -  Prostate-specific antigen (PSA) progression (defined as a minimum of three rising\n                  PSA levels with an interval of ?  week between each determination) within \n                  weeks prior to study drug administration and a PSA value at the screening visit ?\n                   ng/mL.\n\n          -  Subject consents to provide an available tumor specimen in a tissue block or unstained\n             serial slides obtained within  days prior to first dose of study treatment, or\n             subject is an appropriate candidate for tumor biopsy and is amenable to undergoing a\n             tumor biopsy (core needle biopsy or excision) during the screening period.\n\n          -  Subject in a SCCHN monotherapy or combination therapy expansion cohort, is an\n             appropriate candidate for tumor biopsy and consents to undergoing a tumor biopsy (core\n             needle biopsy or excision) during the treatment period as indicated in the Schedule of\n             Assessments.\n\n        Exclusion:\n\n          -  Subject weighs <  kg at screening.\n\n          -  Subject has received investigational therapy (other than an investigational epidermal\n             growth factor receptor tyrosine kinase inhibitor (EGFR TKI) in a subject with EGFR\n             activating mutations) within  days prior to start of study drug.\n\n          -  Subject requires or has received systemic steroid therapy or any other\n             immunosuppressive therapy within  days prior to study drug administration. Subjects\n             using a physiologic replacement dose of hydrocortisone or its equivalent (defined as\n             up to  mg per day of hydrocortisone up to  mg per day of prednisone) are allowed.\n\n          -  Subject has symptomatic central nervous system (CNS) metastases or subject has\n             evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans).\n             Subjects with previously treated CNS metastases are eligible, if subject is clinically\n             stable and have no evidence of CNS progression by imaging for at least  weeks prior\n             to start of study treatment and are not requiring immunosuppressive doses of systemic\n             steroids (>  mg per day of hydrocortisone or >  mg per day of prednisone or\n             equivalent) for longer than  weeks.\n\n          -  Subject has an active autoimmune disease. Subjects with type  diabetes mellitus,\n             endocrinopathies stably maintained on appropriate replacement therapy, or skin\n             disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment\n             are allowed.\n\n          -  Subject was discontinued from prior immunomodulatory therapy due to a grade ? \n             toxicity that was mechanistically related (e.g., immune related) to the agent.\n\n          -  Subject has known history of serious hypersensitivity reaction to a known ingredient\n             of ASP or pembrolizumab or severe hypersensitivity reaction to treatment with\n             another monoclonal antibody.\n\n          -  Subject has a known history of Human Immunodeficiency Virus.\n\n          -  Subject with positive for Hepatitis B virus (HBV) antibodies and surface antigen\n             (including acute HBV or chronic HBV) or Hepatitis C ([HCV]; ribonucleic acid [RNA]\n             detected by qualitative assay). Hepatitis C RNA testing is not required in subjects\n             with negative Hepatitis C antibody testing.\n\n          -  Subject has received a live vaccine against infectious diseases within  days prior\n             to initiation of study treatment.\n\n          -  Subject has a history of drug-induced pneumonitis (interstitial lung disease) or\n             currently has pneumonitis.\n\n          -  Subject has an infection requiring systemic therapy within  days prior to study drug\n             treatment.\n\n          -  Subject has received a prior allogeneic bone marrow or solid organ transplant.\n\n          -  Subject is expected to require another form of antineoplastic therapy while on study\n             treatment.\n\n          -  Subject has had a myocardial infarction or unstable angina within  months prior to\n             the start of study treatment or currently has an uncontrolled illness including, but\n             not limited to symptomatic congestive heart failure, clinically significant cardiac\n             disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social\n             situations that would limit compliance with study requirements.\n\n          -  Any condition that makes the subject unsuitable for study participation.\n\n          -  Subject has had a major surgical procedure and has not completely recovered within \n             days prior to the start of study treatment.
Subject is known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder); subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
Subject meets disease-specific requirements per protocol
Subject is receiving excluded therapy/treatment per protocol
Have histologically confirmed diagnosis of RRP that involves the trachea, lungs, and/or larynx; if a subject is enrolled with laryngeal disease only, the subject must have undergone at least  or more surgeries/procedures in any one year to remove the lesions from their larynx; subjects must have evaluable disease either based on RECIST . and/or endoscopic parameters, as discussed above
Subject has participated in any previous study involving PROSTVAC, Sipuleucel-T or ipilimumab, regardless of whether the subject received PROSTVAC, Sipuleucel-T or ipilimumab
Subject must have the following staging requirements:
RETREATMENT WITH MODIFIED T-CELLS INCLUSION CRITERIA: Subject has modified T cell product available for release
Subject must be stable enough to be expected to complete dosing through the DLT observation period as assessed by the investigator.
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols.
Re-enrollment of a subject that has discontinued the study as a pre-treatment screen failure (i.e. a consented patient who did not receive study drugs) is permitted. If re-enrolled, the subject must be re-consented. Only the screening procedures performed outside of protocol-specified timing must be repeated.
Subject has +FDR with TD
Subject has received:
Presence of another cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpetation of study results.
Subject must have been as fully resected as possible per the physician's judgment.
ADDITIONAL EXCLUSION CRITERIA for subjects on the arm of combination treatment of pembrolizumab and ramucirumab.\r\n* The subject has a known allergy or hypersensitivity to ramucirumab.\r\n* The subject is receiving chronic therapy with any of the following within  days prior to the first dose of trial treatment:\r\n** Nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents), or \r\n** Other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide). Aspirin use at doses up to  mg/day is permitted.\r\n* The subject received previous systemic chemotherapy with a cumulative dose of >  mg/m^ of epirubicin or >  mg/m^ of doxorubicin. \r\n* The subject has a significant bleeding disorder or vasculitis or had a grade >=  bleeding episode within  weeks prior to the first dose of study drug.\r\n* The subject experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within  months prior to the first dose of trial treatment.\r\n* The subject experienced any grade  or  venous thromboembolic event (VTE) that is considered by the investigator to be life-threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within  months prior to the first dose of study drug.\r\n* The subject has symptomatic congestive heart failure (CHF; New York Heart Association IIIV) or symptomatic or poorly controlled cardiac arrhythmia.\r\n* The subject has uncontrolled hypertension, as defined in Common Terminology Criteria for Adverse Events (CTCAE) version ., prior to initiating study treatment, despite antihypertensive intervention. CTCAE version . defines uncontrolled hypertension as grade >  hypertension; clinically, the patient continues to experience elevated blood pressure [systolic >  mmHg and/or diastolic >  mmHg] despite medications).\r\n* The subject has a history of gastrointestinal (GI) perforation or fistula within  months prior to the st dose of treatment.\r\n* The subject has an acute or subacute bowel obstruction or history of chronic diarrhea that is considered clinically significant in the opinion of the investigator.\r\n* The subject has a serious non healing: (a) wound, (b) peptic ulcer, or (c) bone fracture, within  days prior to the first dose of study drug.
The subject must have experienced at least one of the following:
Subject weighs more than  pounds
Inclusion Criteria (All questions must be answered \YES\ in order for the subject to be\n        considered for the study):\n\n          . Is the subject a male or female between and  years of age inclusive who is able to\n             provide informed consent?\n\n          . Does the subject have histologically-confirmed diagnosis of CD-positive DLBCL based\n             on the WHO classification? The diagnosis must be confirmed at the enrolling site.\n             Subjects with history of indolent lymphoma or follicular Grade  lymphoma are not\n             eligible.\n\n          . Does the subject have an ECOG score of ,  or ?\n\n          . Does the subject have an IPI score of at least ?\n\n          . Does the subject have an estimated life expectancy of at least  weeks?\n\n          . Does the subject have adequate organ function as follows:\n\n               . Hepatic: total bilirubin ?. times upper limit of normal (ULN); alanine\n                  transaminase (ALT) and aspartate transaminase (AST) ?. times ULN (< times ULN\n                  if liver involvement)\n\n               . Renal: estimated GFR of > ml/min by Cockcroft- Gault equation\n\n               . Bone marrow: platelets ? x /L, absolute neutrophil count (ANC) ?. x /L,\n                  hemoglobin ? g/dL, unless there is bone marrow involvement\n\n          . If the subject is a male or female with reproductive potential, is he/she willing to\n             use an approved contraceptive method (for example, intrauterine device [IUD], birth\n             control pills, or barrier device) during and for  months after discontinuation of\n             study treatment? Women of childbearing potential must have a negative serum pregnancy\n             test within  days prior to start of treatment.\n\n          . Does the subject have a left ventricular ejection fraction ?% by echocardiography or\n             nuclear medicine multi-gated scan?\n\n          . Is the subject able to swallow tablets?\n\n         . Does the subject have adequate transportation to allow for required follow-up visits?\n\n         . Does the subject agree to have blood stored for possible future biomarker analysis?\n\n        Exclusion Criteria (All must be answered \NO\ in order for the subject to be considered for\n        the study):\n\n          . Has the subject received treatment with an investigational drug within the last \n             days?\n\n          . Is the subject receiving, or has the subject received, any other radiation or systemic\n             anticancer treatment for lymphoma?\n\n          . Is the subject pregnant or breastfeeding?\n\n          . Does the subject have known central nervous system (CNS) involvement?\n\n          . Does the subject have any significant concomitant disorder, including active\n             bacterial, fungal, or viral infection, incompatible with participation in the study?\n\n          . Does the subject have a second primary malignancy (except adequately treated\n             non-melanoma skin cancer)? Patients who have had another malignancy in the past, but\n             have been disease-free for more than  years, are eligible.\n\n          . Is the subject unable to discontinue use of a concomitant medication that is a strong\n             inducer or inhibitor of CYPA? (See Appendix A).\n\n          . Does the subject have a family history of long QT syndrome, or a QTc interval >\n             (males) or  (females) at screening, a history of arrhythmias or a history of\n             unexplained syncope?\n\n          . Must the subject take any medication that can prolong the QT/QTc interval? (See\n             Appendix C)\n\n         . Does the subject have a history of severe allergic or anaphylactic reaction to\n             monoclonal antibody therapy?\n\n         . Does the subject have a confirmed diagnosis of progressive multifocal\n             leukoencephalopathy?\n\n         . Does the subject have a history of grade  or higher peripheral neuropathy?\n\n         . Does the subject have any of the following cardiac disorders: uncontrolled\n             hypertension, unstable angina, myocardial infarction within  weeks of Day, NYHA\n             Grade  or higher congestive heart failure, ventricular arrhythmia requiring\n             medication within  year of Day , NYHA Grade  or higher peripheral vascular disease?\n\n         . Has the subject received a live vaccine within  days of study Day ?\n\n         . Is the subject HIV positive?\n\n         . Does the subject have evidence of chronic hepatitis C infection as indicated by\n             antibody to HCV with positive HCV-RNA?\n\n         . Does the subject have evidence of chronic hepatitis B infection as indicated by\n             either:\n\n               . HBsAg+ or\n\n               . HBcAb+ with HBV-DNA+
Subject has previously received (presence of any of the following will exclude a subject from enrollment):
Subject and subject's parent(s) or legal guardian agree that the subject will not participate in another interventional study while on treatment.
Subject is unlikely to survive  days.
Inclusion Criteria:\n\n        Disease Related\n\n          . Subject has confirmed histologic or cytologic evidence of metastatic pancreatic cancer\n             and has no prior treatment for metastatic pancreatic cancer.\n\n          . Subject has measurable disease using Response Evaluation Criteria in Solid Tumors\n             (RECIST) v ..\n\n          . Subject has a life expectancy of at least  months.\n\n          . Subject has an Eastern Cooperative Oncology Group (ECOG) performance status  or .\n\n             Demographic\n\n          . Males or females ?  years of age\n\n          . Subject must be able to swallow capsules\n\n          . Subject must have adequate venous access for intravenous (IV) infusion\n\n             Laboratory\n\n          . Subject has hemoglobin ? . g/dL at Screening\n\n          . Subject has absolute neutrophil count (ANC) ? . x /L at Screening\n\n         . Subject has platelet count ?  x /L at Screening\n\n         . Subject has serum creatinine ? . times the upper limit of normal (ULN) at Screening.\n             Subjects with serum creatinine levels > . times the ULN must have a -hour urine\n             creatinine clearance ?  mL/min\n\n         . Subject has serum bilirubin ? . times the ULN (except in subjects with Gilbert's\n             Syndrome who must have serum bilirubin < . x ULN)\n\n         . Subject has aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT;\n             SGPT) ? . times the ULN (OR, AST and ALT ?  times the ULN in the presence of known\n             liver metastases)\n\n         . Subject has alkaline phosphatase ? . times the ULN (OR ?  times the ULN in the\n             presence of known liver or bone metastases)\n\n         . Subject has normal coagulation parameters (prothrombin time [PT] and/or international\n             normalized ratio [INR], and partial thromboplastin time [PTT] within normal limits\n             [<. x ULN])\n\n         . Subject has potassium concentration within normal range, or correctable with\n             supplements.\n\n         . Oxygen saturation by pulse oximetry ? % at rest.\n\n         . For women of childbearing potential: Negative serum pregnancy test during screening\n             and negative serum or urine pregnancy test at start of study therapy (Cycle Day ).\n\n             Reproductive\n\n         . For female subjects of childbearing potential, willingness to abstain from\n             heterosexual intercourse or use a protocol-recommended method of contraception from\n             the screening visit throughout the study treatment period and for  days following\n             the last dose of study drug.\n\n         . Female subjects of non-childbearing potential defined as having amenorrhea for at\n             least  consecutive months, a documented hysterectomy, or a documented bilateral\n             oophorectomy)\n\n         . For fertile male subjects having intercourse with females of childbearing potential,\n             willingness to abstain from heterosexual intercourse or use a protocol-recommended\n             method of contraception from the start of study therapy throughout the study treatment\n             period and for  days following the last dose of study drug and to refrain from sperm\n             donation from the start of study treatment throughout the study treatment period and\n             for  days following the last dose of study drug.\n\n             Ethical\n\n         . In the judgment of the investigator, participation in the protocol offers an\n             acceptable benefit-to-risk ratio when considering current disease status, medical\n             condition, and the potential benefits and risks of alternative treatments for the\n             subject's cancer.\n\n         . Before any study-specific procedure, the appropriate written informed consent must be\n             obtained\n\n        Exclusion Criteria:\n\n        Disease Related\n\n          . Subject has primary brain tumors or clinical evidence of active brain metastasis\n\n          . Subject has undergone major surgery within  weeks of the start of study treatment.\n             Laparoscopy and central venous catheter placement are not considered major surgery\n\n             Medications\n\n          . Subject has a history of systemic corticosteroid use within  days before Day  of\n             Cycle \n\n             General\n\n          . Subject has an active infection requiring parenteral or oral antibiotics within \n             weeks before planned start of study therapy\n\n          . Subject has uncontrolled diabetes as assessed by the investigator\n\n          . Subject has a second malignancy other than curatively resected basal cell carcinoma of\n             the skin, squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or\n             other cancers treated with curative intent and no known active disease within  years\n             before planned start of study therapy\n\n          . Subject has an active infection of hepatitis B, hepatitis C or human immunodeficiency\n             virus\n\n          . Female subjects who are pregnant, planning a pregnancy or breast feeding during the\n             study\n\n          . Subject has a high cardiovascular risk, including, but not limited to, subjects with\n             congestive heart failure (New York Heart Association [NYHA] Class III or IV), cardiac\n             arrhythmia, unstable angina, coronary stenting or acute coronary syndromes within \n             months before planned start of study therapy or r myocardial infarction within one\n             year before planned start of study therapy\n\n         . Subject has a history of peripheral artery disease (e.g., claudication, Leo Buerger's\n             disease).\n\n         . Subject has a history of prior allogeneic bone marrow progenitor cell or solid organ\n             transplantation.\n\n         . Subject has known acute or chronic pancreatitis.\n\n         . Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ?\n             NCI CTCAE Grade , despite medical management.\n\n         . Subject has any disorder that may interfere with drug absorption, distribution,\n             metabolism, or excretion (including gastrointestinal surgery and bariatric surgery)\n\n         . All acute toxic effects of any prior antitumor therapy resolved to Grade ?  before\n             the start of study therapy (with the exception of alopecia [Grade  or  permitted],\n             or neurotoxicity [Grade  or  permitted], or anemia [Grade  permitted])\n\n         . Subject has any other medical, psychiatric, or social condition, which in the opinion\n             of the investigator, would preclude participation in the study, pose an undue medical\n             hazard, interfere with the conduct of the study, or interfere with interpretation of\n             the study results\n\n         . Subject has a history of interstitial lung disease, slowly progressive dyspnea and\n             unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary\n             hypersensitivity pneumonitis or multiple allergies. Any lung disease that may\n             interfere with the detection or management of suspected drug-related pulmonary\n             toxicity.\n\n         . Subject is currently enrolled in any other clinical protocol or investigational trial\n             that involves administration of experimental therapy and/or therapeutic devices, or\n             investigational drug.\n\n         . Subject has a history of hypersensitivity to RX-, gemcitabine, azacytidine\n             cytosine arabinoside, paclitaxel, nab-paclitaxel, or their excipients.\n\n         . Subject is unwilling or unable to comply with study requirements or planned\n             unavailability for follow-up assessments.
Subject is HLA-A* positive and subject's tumor shows expression of the MAGE-A RNA or protein.
Subject meets disease-specific requirements per protocol
Subject is receiving excluded therapy/treatment per protocol
Subject re-enrollment: this study permits the re-enrollment of a subject that has discontinued the study as a screen failure (ie, subject has not been randomized / has not been treated); if re-enrolled, the subject must be re-consented
Re-enrollment of a subject that has discontinued the study as a pre-treatment screen failure (i.e. a consented patient who did not receive avelumab) is permitted; if re-enrolled, the subject must be re-consented; only the screening procedures performed outside of protocol-specified timing must be repeated
This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been randomized / has not been treated); if re-enrolled, the subject must be re-consented
Subject meets the reproductive criteria as follows:
The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression; or the subject is currently receiving any drug or supplement which is known to be associated with systemic immune suppression including those drugs which are prescribed for solid organ or stem cell transplant, autoimmune/inflammatory disorders, or other related medical conditions
The subject has been diagnosed and treated at an external facility, and the resulting tissue specimen is of insufficient quality such that it precludes clinical sequencing or any other necessary study procedure, and the subject is unwilling to undergo an additional biopsy procedure
The subject is a prisoner
The subject is pregnant, as defined by a presumptive sign of pregnancy such as missed menses or a positive pregnancy test; NOTE: female subjects of childbearing potential are required to have a negative qualitative serum pregnancy test at the time of enrollment and within twenty-four () hours prior to the first dose of the investigational product\r\n* Female subject of childbearing potential is defined as follows:\r\n** Subject with regular menses\r\n** Subject with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding\r\n** Subject with history of tubal ligation\r\n* Female subject not of childbearing potential is defined as follows:\r\n** Subject who has undergone hysterectomy and/or bilateral oophorectomy\r\n** Subject who is post-menopausal, which is defined as amenorrhea for at least one () year in a female subject who is greater than forty-five (> ) years old
Female subject not of childbearing potential is defined as follows:\r\n* Subject who has undergone hysterectomy and/or bilateral oophorectomy\r\n* Subject who is post-menopausal, which is defined as amenorrhea for at least one () year in a female subject who is greater than forty-five (> ) years old
Subject is a prisoner
Inclusion Criteria:\n\n        Subject must have had a diagnosis of primary or secondary warm antibody AIHA.\n\n        - Must have failed at least  prior treatment regimen for AIHA.\n\n        Exclusion Criteria:\n\n          -  Subject with cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or\n             paroxysmal cold hemoglobinuria.\n\n          -  Subject with a platelet count of < ,/?L.\n\n          -  Subject has AIHA secondary to autoimmune disease, including systemic lupus\n             erythematosis (SLE), or lymphoid malignancy and the underlying disease is not stable\n             or is not well-controlled on current therapy.\n\n          -  Subject has uncontrolled or poorly controlled hypertension, defined as systolic blood\n             pressure ?  mmHg, or diastolic blood pressure ?  mmHg.
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols
If the planned radiation field includes any part of the esophagus and the subject has symptoms of ongoing esophagitis, the subject is not eligible, unless an esophageal endoscopy rules out the presence of esophagitis
Subject has history of major immunologic reaction to any Immunoglobulin G (IgG) containing agent.
Subject has any underlying conditions, which would contraindicate therapy with study treatment
Subject must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects).
RETREATMENT WITH MODIFIED T CELLS: Subject has modified T cell product available for release
RETREATMENT WITH MODIFIED T CELLS: Subject has evidence of persistent NB
History of venous or arterial thromboembolism, unless:\r\n* Line-related thrombosis without embolus occurring >=  year prior to screening\r\n* Complications resulting from atherosclerotic coronary artery disease, peripheral vascular disease, or cerebrovascular disease (including infarction) are not considered exclusion criteria unless in the opinion of the principal investigator or lead associate investigator their clinical consequences in a particular subject places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
The subject presents with:
) Subject has [follicular lymphoma that has progressed within  months of first diagnosis and treatment with combination chemoimmunotherapy] (e.g. R-bendamustine, R-CHOP) OR Progression of iNHL within  months of completion of second or later line therapy containing both an anti-CD antibody and alkylating agent OR Progression of iNHL at any point following autologous transplantation. ) Subject has [measurable disease]. ) Subject has no known presence or history of CNS involvement by lymphoma. ) If subject is on conventional systemic therapy or systemic inhibitory/stimulatory immune checkpoint therapy, subject is able to stop conventional therapy  weeks or  half-lives, whichever is shorter, or immune checkpoint therapy  half-lives prior to planned leukapheresis. ) Subject has ECOG performance status of - and adequate renal, hepatic, pulmonary, and cardiac function ) Subject is not pregnant or breastfeeding (female subjects only) and is willing to use birth control from the time of consent through  months following CAR T cell infusion (both male and female subjects).B
Inclusion Criteria:\n\n        All subjects must meet the following criteria for admission into the study:\n\n          . Signed informed consent has been obtained.\n\n          . Subject is at least  years of age.\n\n          . Diagnosis of mycosis fungoides (MF) or Szary syndrome (SS) will be based on a\n             combination of histological, clinical, and immunophenotypical criteria. The\n             histological criteria will be based on skin biopsy from the most representative skin\n             area. The diagnostic criteria used for each subject will be specified in the case\n             report forms and the specific classification of MF or SS will be identified. The TNMB\n             system will be used to classify the stage of disease (See Section . for details).\n\n          . Completion of the mSWAT assessment.\n\n          . A history of pruritus that meets following criteria:\n\n             At Screening Day -:\n\n               -  present on a daily basis for greater than one month prior to Screening Day -,\n\n               -  NRS for Pruritus score ? as rated by the subject at the Day - Visit. Note: If\n                  the score is < and subject is taking or has taken a medication which may be\n                  affecting pruritus (e.g. systemic antihistamine or topical steroid), and if\n                  Investigator and subject agree, subject may washout or continue washout of\n                  medication and return for Day - Visit procedures after washout.\n\n             At Baseline Period  Day :\n\n               -  NRS for Pruritus score of at least  recorded in the subject diary on at least \n                  of the  days preceding Baseline Period  Day .\n\n          . Pruritic treatment area of -% of the subject's total treatable body surface area.\n\n          . Subject can be expected to reliably follow treatment instructions and visit schedule.\n\n          . Non-pregnant, non-lactating females of childbearing potential who agree to use\n             medically acceptable forms of birth control (abstinence, hormonal contraceptives,\n             diaphragm with spermicide, condom with spermicide, or intrauterine device) throughout\n             the study or females of non-childbearing potential (surgically sterile [hysterectomy\n             or bilateral tubal ligation] or post-menopausal ?  year). A negative urine pregnancy\n             test must be confirmed at Baseline screening for all female subjects who are not\n             post-menopausal >  year or surgically sterile.\n\n          . The subject agrees not to begin any new concomitant medications during their\n             participation in the study, with the exception of medications necessary to treat\n             infection, and to continue any concomitant medication throughout the study.\n\n         . Subject has no visual or motor impairments that will make it difficult to complete the\n             Daily Diary or apply the study medication.\n\n         . Subject is able to speak, read, and write English and agrees to participate and comply\n             with the study procedures.\n\n         . Subject has a body mass index (BMI) between . and . kglm (see Appendix C, Body\n             Mass Index Table) (subjects in PK subset only).\n\n        Exclusion Criteria:\n\n        Subjects meeting any of the following criteria will be excluded from study participation:\n\n          . Pregnant or lactating female.\n\n          . History of clinically significant heart failure.\n\n          . Myocardial infarction within the past six months.\n\n          . A history of ventricular arrhythmia requiring treatment.\n\n          . Any medical condition which would, in the Investigator's opinion, preclude the subject\n             from successfully participating in the study.\n\n          . A known allergy to naloxone hydrochloride or any excipient in the formulation.\n\n          . Previous naloxone use for pruritus.\n\n          . Positive urine drug screen at Day  for opiates. Positive urine drug screen for\n             anything other than opiates not explained, e.g., by concomitant medication, would also\n             exclude the subject.\n\n          . Treatment with any of the following during the restricted time period prior to Day -,\n             and at any time during the study, is not allowed:\n\n        Medication/Treatment Restriction:\n\n        Systemic narcotic analgesics (e.g. morphine, codeine)  days, Topical antihistamines to any\n        skin surface [e.g. Zonalon (doxepin)]  days, Other investigational drugs (excluding any\n        therapies for the treatment of MF or SS)  days
Malignancy other than disease under study with the exception of those from which the subject has been disease-free for more than  years and not expected to affect the safety of the subject or the endpoints of the trial.
Subject has HNSCC with carotid artery encasement
The presence of any of the following will exclude a subject from enrollment:
The subject presents with:
Subject is undergoing robotic partial nephrectomy being performed by participating surgeon
Subjects with polymicrobial CRBSI/CLABSI caused by pathogens that would require multiple antibiotics to be used for adequate lock therapy treatment. For example, a subject with methicillin-resistant Staphylococcus aureus and Escherichia coli requiring treatment with vancomycin and meropenem would be excluded from the study. A subject with S. aureus and Staphylococcus epidermidis, where both are identified as pathogens and where both could be treated with vancomycin, would be eligible;
Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least  years.
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          . Subject is ?  years of age the time of signing the informed consent form (ICF).\n\n          . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          . Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements.\n\n          . Subject has newly diagnosed, primary (ie, de novo) or secondary (progression of MDS or\n             myeloproliferative neoplasms [MPN], or therapy-related) AML according to the WHO\n             classification with ? % leukemic blasts in the bone marrow: -Have an Isocitrate\n             dehydrogenase  (IDH) or Isocitrate dehydrogenase  (IDH) gene mutation (R, R,\n             or R)\n\n               -  IDH mutational status will be assessed locally; for sites without local testing\n                  capabilities, a referral lab will be identified.\n\n                    -  By the investigator's assessment who are not candidates to receive intensive\n                       Inductive chemotherapy (IC).\n\n          . Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ,  or\n             .\n\n          . Subject has adequate organ function defined as:\n\n               -  Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase\n                  (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ?  x ULN, unless considered\n                  due to leukemic organ involvement.\n\n               -  Serum total bilirubin < . x ULN. Higher levels are acceptable if these can be\n                  attributed to ineffective erythropoiesis,  times the upper limit of normal for\n                  Gilbert's syndrome (eg, a gene mutation in UGTA), or leukemic organ\n                  involvement.\n\n               -  Serum creatinine <  x ULN or creatinine clearance >  mL/min based on the\n                  Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR):\n\n             GFR (mL/min/. m) =   (Scr)-.  (Age)-.  (. if female)  (. if\n             African American)\n\n          . Agree to serial bone marrow aspirate/biopsies.\n\n          . Females of childbearing potential (FCBP)* may participate, providing they meet the\n             following conditions:\n\n               -  Agree to practice true abstinence ** from sexual intercourse or to use highly\n                  effective contraceptive methods (eg, combined [containing estrogen and\n                  progestogen] or progestogen only associated with inhibition of ovulation, oral,\n                  injectable, intravaginal, patch, or implantable hormonal contraceptive; bilateral\n                  tubal occlusion; intra-uterine device; intrauterine hormone-releasing system; or\n                  male partner sterilization [note that a vasectomized partner is a highly\n                  effective birth control method provided that partner is the sole sexual partner\n                  of the FCBP trial participant and that a vasectomized partner has received\n                  medical assessment of the surgical success]) at screening and throughout the\n                  study, and for at least  months following the last study treatment; and\n\n               -  Have a negative serum ?-subunit of human chorionic gonadotropin (?-hCG) pregnancy\n                  test (sensitivity of at least  mIU/mL) at screening; and\n\n               -  Have a negative serum or urine (investigator's discretion under local\n                  regulations) ?-hCG pregnancy test (sensitivity of at least  mIU/mL) within \n                  hours prior to the start of study treatment in the Treatment Period (note that\n                  the screening serum pregnancy test can be used as the test prior to the start of\n                  study treatment in the Treatment Period if it is performed within the -hour\n                  timeframe).\n\n          . Male subjects must agree to practice true abstinence from sexual intercourse or agree\n             to the use of highly effective contraceptive methods (as described above) with\n             non-pregnant female partners of child bearing potential at screening and throughout\n             the course of the study and should avoid conception with their partners during the\n             course of the study and for at least  months following the last study treatment (\n             months following last dose of azacitidine in Canada). Furthermore, the male subject\n             must agree to use a condom while treated with azacitidine and for at least  months\n             following the last azacitidine dose.\n\n        Exclusion Criteria:\n\n        - The presence of any of the following will exclude a subject from enrollment:\n\n          . Subject is suspected or proven to have acute promyelocytic leukemia based on\n             morphology, immunophenotype, molecular assay, or karyotype.\n\n          . Subject has AML secondary to chronic myelogenous leukemia (CML).\n\n          . Subject has received a targeted agent against an Isocitrate dehydrogenase  (IDH) or\n             Isocitrate dehydrogenase  (IDH) mutation.\n\n          . Subject has received prior systemic anticancer therapy, HSCT, or radiotherapy for AML.\n\n             Note: Hydroxyurea is allowed prior to enrollment for the control of peripheral\n             leukemic blasts in subjects with leukocytosis. (however, hydroxyurea should not be\n             given within  hours prior to and after administration of azacitidine). For subjects\n             with secondary AML (eg, MDS or MPN) treatment for prior cancer is not exclusionary;\n             full treatment information will be collected within the CRF. The use of all trans\n             retinoic acid (ATRA) for suspected APL is not exclusionary provided it is discontinued\n             prior to initiation of treatment in the protocol.\n\n          . Subject has received more than  cycle of prior treatment with azacitidine, or subject\n             has received any prior treatment with decitabine for Myelodysplastic syndromes (MDS).\n\n             - Clarification: Subjects with newly diagnosed Acute myeloid leukemia (AML) who are\n             currently receiving their st cycle of azacitidine ( days) can be screened for the\n             study. On study, Cycle  must be started at  days (+/-  days) after initiation of\n             the pre-study azacitidine.\n\n          . Subject has or is suspected of having central nervous system (CNS) leukemia.\n             Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is\n             suspected during screening.\n\n          . Subject has immediate life-threatening, severe complications of leukemia such as\n             uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated\n             intravascular coagulation.\n\n          . Subject has significant active cardiac disease within  months prior to the start of\n             study treatment, including New York Heart Association (NYHA) class III or IV\n             congestive heart failure; acute coronary syndrome (ACS); and/or stroke; or left\n             ventricular ejection fraction (LVEF) < % by echocardiogram (ECHO) or multi-gated\n             acquisition (MUGA) scan obtained within  days prior to the start of study treatment.\n\n          . Subject has prior history of malignancy, other than MDS, Myeloproliferative neoplasm\n             (MPN), or AML, unless the subject has been free of the disease for ?  year prior to\n             the start of study treatment. However, subjects with the following history/concurrent\n             conditions are allowed:\n\n               -  Basal or squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histologic finding of prostate cancer (Ta or Tb using the tumor,\n                  node, metastasis clinical staging system)\n\n         . Subject is known seropositive for or has active viral infection with human\n             immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or\n             hepatitis C virus (HCV)\n\n         . Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other\n             conditions that limit the ingestion or gastrointestinal absorption of drugs\n             administered orally\n\n         . Subject has uncontrolled hypertension (systolic blood pressure [BP] >  mmHg or\n             diastolic BP >  mmHg)\n\n         . Subject is taking the following sensitive CYP substrate medications that have a narrow\n             therapeutic range are excluded from the study unless the subject can be transferred to\n             other medications at least  half-lives prior to the start of study treatment:\n             phenytoin (CYPC), S-mephenytoin (CYPC), thioridazine (CYPD), theophylline, and\n             tizanidine (CYPA).\n\n         . Subject is taking the breast cancer resistance protein (BCRP) transporter-sensitive\n             substrate rosuvastatin; subject should be excluded from the study unless he/she can be\n             transferred to other medications at least  half-lives prior to the start of study\n             treatment.\n\n         . Subject has active uncontrolled systemic fungal, bacterial, or viral infection\n             (defined as ongoing signs/symptoms related to the infection without improvement\n             despite appropriate antibiotics, antiviral therapy, and/or other treatment).\n\n         . Subject has known or suspected hypersensitivity to any of the components of study\n             therapy.\n\n         . Subject is taking medications that are known to prolong the QT interval unless he/she\n             can be transferred to other medications within ?  half-lives prior to the start of\n             study treatment.\n\n         . Subject has Heart rate-corrected QT (QTc) interval (ie, Fridericia's correction\n             [QTcF]) ?  ms or other factors that increase the risk of QT prolongation or\n             arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval\n             syndrome) at screening.\n\n         . Female subject who is pregnant or lactating.\n\n         . Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study.\n\n         . Subject has any condition, including the presence of laboratory abnormalities that\n             places the subject at unacceptable risk if he/she were to participate in the study.\n\n         . Subject has any condition that confounds the ability to interpret data from the study.
Subject has air leak present on at least the th day following origination.
Subject has air leak only on forced exhalation or cough
Subject has sepsis
Subject has pneumonia
Subject has a primary pneumothorax
The subject has a history of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression; or the subject is currently receiving any drug or supplement which is known to be associated with systemic immune suppression including those drugs which are prescribed for solid organ or stem cell transplant, autoimmune/inflammatory disorders, or other related medical conditions
The subject is a prisoner
Note: Female subjects of childbearing potential are required to have a negative qualitative serum pregnancy test at the time of enrollment and within twenty-four () hours prior to the first dose of the investigational product\r\n* Female subject of childbearing potential is defined as follows:\r\n** Subject with regular menses\r\n** Subject with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding\r\n** Subject with history of tubal ligation\r\n* Female subject not of childbearing potential is defined as follows:\r\n** Subject who has undergone hysterectomy and/or bilateral oophorectomy\r\n** Subject who is post-menopausal, which is defined as amenorrhea for at least one () year in a female subject who is greater than forty-five (> ) years old
Subject meets institutional requirements for IL- therapy
At least  days must have passed since the first cell infusion and the subject must not have experienced a dose limiting toxicity (DLT) in this time
Subject is eligible for pre-selected salvage chemotherapy.
Subject has had prior treatment with lenalidomide. . Subject is pregnant or lactating.
The presence of any of the following will exclude a subject from enrollment:
Subject has a history of well-documented prior veno-occlusive disease (VOD).
High-grade Ta papillary disease based on a biopsy within  weeks of the initial dose of study treatment. If multiple bladder biopsies are required to confirm eligibility, the last bladder biopsy to the initial dose of study treatment must be within  weeks. This diagnosis must be confirmed by the independent central pathology reviewer prior to subject enrollment. A subject with persistent T disease on the second (i.e., restaging) TURBT may be enrolled in this study only if the investigator documents the subject declines cystectomy.
Subject has history of Myeloproliferative Neoplasm (MPN).
If the subject has RS, the subject must have had ? prior treatment with a combination chemoimmunotherapy regimen.
Subject has a known dysfibrinogenemia, hypofibrinogenemia or a fibrinogenemia, without preoperative correction of fibrinogen levels.
Subject has a confirmed diagnosis of advanced unresectable solid tumors in the target subject population within the parameters mentioned:
If subject has received solvent-based paclitaxel (TAXOL) or docetaxel as adjuvant chemotherapy, subject must not have relapsed with breast cancer within  months of completing said therapy.
Subject has a history of peripheral artery disease (eg, claudication, Leo Buerger's disease).
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study (with the\n        enrollment date defined as the date in which the subject is assigned a cohort in Integrated\n        Response Technology [IRT]) and receive their first dose of luspatercept:\n\n          . Subject is ? years of age at the time of signing the informed consent form (ICF).\n\n          . Subject has Myeloproliferative neoplasm (MPN)-associated myelofibrosis (PMF, post-\n             Post-polycythemia vera myelofibrosis (PV MF), and/or Post-essential thrombocythemia\n             myelofibrosis (post-ET MF)) as confirmed from the most recent local bone marrow biopsy\n             report according to the World Health Organization  criteria.\n\n          . Subject has anemia defined as:\n\n               . Cohorts  and A\n\n                    -  Obtain ?  Hemoglobin (Hgb) levels of ? . g/dL recorded on ?  different\n                       days, including the day of dosing, in the -day period immediately up to\n                       the CD date. There must be ?  days in between each Hgb measurement. No\n                       subjects with an interval ?  days between hemoglobin measurements will be\n                       enrolled.\n\n                    -  There must not be any Red blood cell (RBC) transfusions within the -day\n                       period immediately up to the CD date.\n\n               . Cohorts  and B\n\n                    -  Average RBC-transfusion frequency:  to  RBC units/ days over at least\n                       the  days immediately up to the CD date. There must be no interval > \n                       days without ?  RBC-transfusion.\n\n                    -  Subjects must have a Hgb value of <  g/dL on CD prior to luspatercept\n                       administration.\n\n                    -  Only RBC transfusions given when the Hgb ? . g/dL are scored in\n                       determining eligibility.\n\n                    -  RBC transfusions given because of bleeding, infection, or chemotherapy\n                       induced anemia are not scored in determining eligibility.\n\n          . Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ? .\n\n          . Subject is not anticipated during the  months from the CD date to receive a\n             hematopoietic cell transplant.\n\n          . A female of childbearing potential (FCBP) for this study is defined as a female who:\n             ) has achieved menarche at some point, ) has not undergone a hysterectomy or\n             bilateral therapy does not rule out childbearing potential) for at least \n             consecutive months (ie, has had menses at any time in the preceding  consecutive\n             months). FCBP participating in the study must:\n\n               . Have  negative pregnancy tests as verified by the Investigator prior to starting\n                  study therapy. She must agree to ongoing pregnancy testing during the course of\n                  the study, and after end of study treatment. This applies even if the subject\n                  practices true abstinence* from heterosexual contact.\n\n               . Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed on a monthly basis and source documented) or agree to use, and be able\n                  to comply with, effective contraception** without interruption,  days prior to\n                  starting investigational product, during the study therapy (including dose\n                  interruptions), and for  weeks (approximately  times the mean terminal\n                  halflife of luspatercept based on multiple-dose pharmacokinetics [PK] data) after\n                  discontinuation of study therapy.\n\n          . Male subjects must:\n\n             a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to\n             use a condom during sexual contact with a pregnant female or a female of childbearing\n             potential while participating in the study, during dose interruptions and for at least\n              weeks (approximately  times the mean terminal half-life of luspatercept based on\n             multiple-dose PK data) following investigational product discontinuation, even if he\n             has undergone a successful vasectomy\n\n          . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          . Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements.\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment (with the\n        enrollment date defined as the date in which the subject is assigned a cohort in Integrated\n        Response Technology (IRT)):\n\n          . Subject use of hydroxyurea or other drugs with potential effects on hematopoiesis or\n             ongoing adverse events from previous treatment ?  days immediately up to the\n             enrollment date.\n\n             a. Systemic corticosteroids are permitted for nonhematological conditions providing\n             the subject is receiving a stable or decreasing dose for ?  days immediately up to\n             enrollment and is receiving a constant dose equivalent to ?  mg prednisone for the\n              days immediately up to enrollment.\n\n          . Cohort  and  only: subjects treated with Janus kinase  gene (JAK) inhibitors ? \n             days immediately up to the enrollment date or if anticipated/substantial likelihood\n             for subject to receive ruxolitinib within the first  days on the study.\n\n          . Cohort  only: subjects not receiving a stable dose of ruxolitinib as part of their\n             standard-of-care therapy for  days immediately up to the enrollment date.\n\n          . Subject use of ESAs or androgenic steroids ?  days immediately up to the enrollment\n             date.\n\n          . Initiation of iron chelation therapy (ICT) or change with ICT dose within ?  days\n             up to the enrollment date.\n\n          . Subject with anemia from iron deficiency, B and folate deficiencies, hemolytic\n             anemia, infection, or bleeding.\n\n          . Pregnant or breastfeeding females.\n\n          . Subject with blood myeloblasts ? %.\n\n          . Subject with major surgery within  weeks up to the enrollment date. Subject must have\n             completely recovered from any previous surgery immediately up to the enrollment date.\n\n         . Subject with prior history of malignancies, other than disease under study, unless the\n             subject has been free of the disease for ?  years. However, subject with the\n             following history/concurrent conditions is allowed:\n\n               -  Basal or squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histologic finding of prostate cancer (Ta or Tb using the tumor,\n                  nodes, metastasis [TNM] clinical staging system)\n\n         . Subject with prior therapy of luspatercept or sotatercept.\n\n         . Subject participation in any other clinical protocol or investigational trial that\n             involves administration of experimental therapy and/or therapeutic devices within \n             days immediately up to the enrollment date.\n\n         . Subject with prior hematopoietic cell transplant.\n\n         . Subject with any of the following laboratory abnormalities:\n\n               -  Neutrophils <  x /L\n\n               -  White blood count (WBC) >  x /L\n\n               -  Platelets\n\n                    -  Cohorts  and : <  x /L\n\n                    -  Cohort A and B: <  x /L\n\n                    -  All Cohorts: >  x /L\n\n               -  Estimated glomerular filtration rate <  mL/min/. m (via the -variable\n                  modification of diet in renal disease [Modification of diet in renal disease\n                  (MDRD)] formula)\n\n               -  Aspartate aminotransferase (AST) or alanine transaminase (ALT) > . x upper\n                  limit of normal (ULN)\n\n               -  Direct bilirubin ?  x ULN\n\n                  o higher levels are acceptable if these can be attributed to active red blood\n                  cell precursor destruction within the bone marrow (ie, ineffective\n                  erythropoiesis)\n\n               -  Uncontrolled hyperthyroidism or hypothyroidism\n\n         . Subject with stroke, deep venous thrombosis, pulmonary or arterial embolism within \n             months immediately up to the enrollment date.\n\n         . Subject with diastolic blood pressure ?  mmHg or systolic blood pressure ?  mmHg\n             measured during the Screening Period despite appropriate treatment.\n\n         . Subject with inadequately controlled heart disease and/or have a known left\n             ventricular ejection fraction <%.\n\n         . Subject with history of severe allergic or anaphylactic reactions or hypersensitivity\n             to recombinant proteins or excipients in the investigational product (see luspatercept\n             Investigator's Brochure (IB)).\n\n         . Subject with uncontrolled systemic fungal, bacterial, or viral infection (defined as\n             ongoing signs/symptoms related to the infection without improvement despite\n             appropriate antibiotics, antiviral therapy, and/or other treatment).\n\n         . Subject with human immunodeficiency virus (HIV), evidence of active infectious\n             Hepatitis B (HepB), and/or evidence of active Hepatitis C (HepC).\n\n         . Subject with any significant medical condition, laboratory abnormality, psychiatric\n             illness, or is considered vulnerable by local regulations (eg, imprisoned or\n             institutionalized) that would prevent the subject from participating in the study.\n\n         . Subject with any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study.\n\n         . Subject with any condition or concomitant medication that confounds the ability to\n             interpret data from the study.\n\n         . Subject on anticoagulant therapy not under appropriate control or subject not on a\n             stable dose of anticoagulant therapy for ?  weeks up to the enrollment date.\n\n         . Subject on anagrelide within  days immediately up to the enrollment date.\n\n         . Subject with a major bleeding event (defined as symptomatic bleeding in a critical\n             area or organ and/or bleeding causing a decrease in hemoglobin of ? g/dL or leading\n             to transfusion of ?  units of packed red cells) in the last  months prior to\n             enrollment.
Female subject who is pregnant or breast-feeding, or any subject expecting to conceive or father a child during this study;
The presence of any of the following will exclude a subject from enrollment:
Male subject must:
The subject has a severe concurrent disease, infection, or comorbidity that would make the subject inappropriate for enrollment.
The subject has had a hypoglycemic episode requiring medical intervention while on insulin (or other anti-diabetic) treatment within  months before Day .
Subject must have received at least  months of chemotherapy
Subject has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the subject to receive an experimental research drug
Subject who fulfills the laboratory requirements as per protocol
Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, has not been treated). If re-enrolled, the subject must be re-consented.
Subjects may be eligible to receive MK- in the second course phase of this study if the study remains open and the subject meets the following conditions:
Subject has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the subject to receive an experimental research drug
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols
Subject has an advance directive to withhold life-sustaining treatment.
Subject is know to have active tuberculosis, leishmaniasis, or listeriosis
Subject is considered an adult according to local regulation at the time of obtaining informed consent.
Subject has any of the following comorbidities:
 Subject is undergoing a laparoscopic, thoracoscopic, or robotic surgical procedure;
Subject has a known psychiatric disorder, which in the opinion of the Principal Investigator, would preclude the subject from completing this clinical study;
Subject has religious or other objections to porcine, bovine, or human components;
Subject in whom the Investigator is able to identify a TBS for which any applicable conventional means for hemostasis are ineffective or impractical; and
Patients with stable brain metastases will be allowed provided the following criteria are met:\r\n* Brain radiation was already provided at least  weeks prior to initiating study treatment\r\n* The subject has no new or progressive neurologic symptoms AND neurological symptom stability for the last  weeks prior to the study\r\n* The subject has been off of corticosteroids for at least  days prior to trial treatment\r\n* The subject does not have carcinomatous meningitis
Inclusion Criteria:\n\n        A subject will be eligible for inclusion in this study only if all of the following\n        criteria are met:\n\n          . Male or female subject is between  and  years of age at the time of signing the\n             Informed Consent Form (ICF).\n\n          . Subject has definitive histologically or cytologically confirmed metastatic pancreatic\n             adenocarcinoma.\n\n          . Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) -.\n\n          . Subject has one or more tumors measurable by CT scan (or (MRI), if allergic to CT\n             contrast media) as defined by Response Evaluation Criteria In Solid Tumors (RECIST)\n             ..\n\n          . Subject has the following blood counts / Hemoglobin (Hgb) at screening:\n\n               -  Absolute neutrophil count (ANC) ? .  ^/L;\n\n               -  Platelet count ? ,/mm (  ^/L);\n\n               -  Hgb ? LLN or  g/dL.\n\n          . Subject has the following blood chemistry levels at screening:\n\n               -  AST (SGOT), ALT (SGPT) ? . x upper limit of normal range (ULN); if hepatic\n                  metastases present ? . x ULN\n\n               -  Total bilirubin ? . X ULN\n\n               -  Creatinine clearance ?  mL/min (by Cockroft-Gault)\n\n               -  Albumin ? . grams/dL.\n\n          . Females of childbearing potential (FOCBP) [defined as a sexually mature woman who ()\n             have not undergone hysterectomy (the surgical removal of the uterus) or bilateral\n             oophorectomy (the surgical removal of both ovaries) or () have not been naturally\n             postmenopausal for at least  consecutive months (ie, has had menses at any time\n             during the preceding  consecutive months)] must:\n\n               -  Have a negative pregnancy test (?-human chorionic gonadotropin [? -hCG]) as\n                  verified by the study doctor within  hours prior to starting study therapy\n\n               -  Commit to complete abstinence from heterosexual contact, or agree to use medical\n                  doctor-approved contraception throughout the study without interruption; while\n                  receiving study medication and for at least  months following last dose of study\n                  IP.\n\n          . Males must practice complete abstinence or agree to use a condom (even if he has\n             undergone a successful vasectomy) during sexual contact with a pregnant female or a\n             female of childbearing potential while participating in the study, during dose\n             interruptions and for at least  months following last dose of study IP.\n\n          . Subject has no clinically significant abnormalities in urinalysis results at baseline.\n\n         . Subject is able to adhere to the study visit schedule and other protocol requirements.\n\n         . Subject understands the nature of the study, and has agreed to participate in the\n             study, and has voluntarily signed the ICF prior to participation in any study-related\n             activities.\n\n         . Subject must consent to provide protocol-mandated tumor and blood samples for\n             molecular analysis.\n\n         . Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements\n\n        Exclusion Criteria:\n\n        A subject will not be eligible for inclusion in this study if any of the following criteria\n        apply:\n\n          . Subject has received previous systemic chemotherapy or investigational therapy (other\n             than that as a radiosensitizer concomitant with radiotherapy) for the treatment of\n             pancreatic adenocarcinoma, including neo-adjuvant or adjuvant therapy.\n\n          . Subject has known brain metastases unless previously treated and controlled for a\n             minimum of  weeks prior to enrollment. Subject is not receiving corticosteroids with\n             no evidence of cerebral edema.\n\n          . Pre-existing peripheral neuropathy > Grade \n\n          . Subject with unstable stent.\n\n          . History of malignancy in the last  years. Subjects with prior history of in situ\n             cancer or basal or squamous cell skin cancer are eligible. Subjects with other\n             malignancies are eligible if they were cured by surgery alone or surgery plus\n             radiotherapy and have been continuously disease-free for at least  years.\n\n          . Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring\n             systemic therapy , defined as ongoing signs/symptoms related to the infection without\n             improvement despite appropriate antibiotics, antiviral therapy, and/or other\n             treatment.\n\n          . Subject has known historical or active infection with human immunodeficiency virus\n             (HIV), hepatitis B, or hepatitis C or subject receiving immunosuppressive or\n             myelosuppressive medications that would, in the opinion of the Investigator, increase\n             the risk of serious neutropenic complications.\n\n          . Subject has undergone major surgery, other than diagnostic surgery (ie, surgery done\n             to obtain a biopsy for diagnosis without removal of an organ), within  weeks prior to\n             Day  of treatment in this study or surgical wound has not fully healed.\n\n          . Subject has a history of allergy or hypersensitivity to any of the IP or any of their\n             excipients, or the subject exhibits any of the events outlined in the\n             Contraindications or Special Warnings and Precautions sections for and of the\n             products' Summary of Product Characteristics or Prescribing Information.\n\n         . History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).\n\n         . Subject with a history of interstitial lung disease, history of slowly progressive\n             dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis,\n             pulmonary hypersensitivity pneumonitis or multiple allergies that in the opinion of\n             the Investigator may put them at increased risk of interstitial pneumonitis.\n\n         . Subject with high cardiovascular risk, including, but not limited to:\n\n               -  uncontrolled hypertension\n\n               -  unstable angina\n\n               -  diagnosis of ischemic heart disease\n\n               -  heart disease of New York Heart Association functional classification ?  (see\n                  Appendix C)\n\n               -  prior history of hemorrhagic or thrombolytic stroke\n\n               -  prior exposure to anthracycline\n\n               -  history of peripheral artery disease (eg, claudication, Leo Buerger's disease)\n\n               -  any of the following within the prior  months\n\n               -  coronary stenting\n\n               -  myocardial infarction\n\n               -  coronary bypass surgery\n\n         . Recent history of clinically significant hemoptysis.\n\n         . Pregnant and nursing (lactating) women.\n\n         . Any significant medical condition, laboratory abnormality, or psychiatric illness that\n             would prevent the subject from participating in the study.\n\n         . Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study.\n\n         . Subject has any condition that confounds the ability to interpret data from the study.
Subject underwent transplantation at least  months prior to enrollment
Subject must have received no prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Subject may have been treated for prior Myelodysplastic Syndrome.
Subject has been evaluated by a local neurologist prior to study entry who has determined the subject has at least one risk factor for seizure including:
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          . Subject is ?  years of age at the time of signing the informed consent form (ICF).\n\n          . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          . Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements.\n\n          . Eastern Cooperative Oncology Group (ECOG) performance status score of ,  or .\n\n          . Subjects must have a documented diagnosis of MM and measurable disease at enrollment.\n\n          . Subjects must have the following laboratory values:\n\n               -  Absolute neutrophil count (ANC) ? . x /L without growth factor support for\n                  ?  days (?  days for pegfilgrastim).\n\n               -  Hemoglobin (Hgb) ?  g/dL.\n\n               -  Platelets (plt) ?  x /L without transfusion for ?  days (?  x /L for\n                  subjects with > % plasma cells in bone marrow).\n\n               -  Corrected serum calcium ? . mg/dL (? . mmol/L).\n\n               -  -hr creatinine clearance (CrCl) ?  mL/min.\n\n               -  AST/SGOT and ALT/SGPT ? . x upper limit of normal (ULN).\n\n               -  Serum bilirubin ? . x ULN.\n\n               -  Uric acid ? . mg/dL ( ?mol/L).\n\n               -  PT/INR < . x ULN and partial thromboplastin time (PTT) < . x ULN, (for\n                  subjects not receiving therapeutic anticoagulation).\n\n          . Females of childbearing potential (FCBP) must:\n\n               . Have two negative pregnancy tests as verified by the Investigator prior to\n                  starting study therapy. She must agree to ongoing pregnancy testing during the\n                  course of the study, and after discontinuation of CC-. This applies even if\n                  the subject practices true abstinence* from heterosexual contact.\n\n               . Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed on a monthly basis and source documented) or agree to use, and be able\n                  to comply with, two reliable forms of contraception without interruption,  days\n                  prior to starting CC-, during the study therapy (including during dose\n                  interruptions), and for  days after discontinuation of study therapy.\n\n          . Male subjects must:\n\n               . Practice true abstinence* (which must be reviewed on a monthly basis) or agree to\n                  use of a condom during sexual contact with a pregnant female or a female of\n                  childbearing potential while participating in the study (even during dose\n                  interruptions) and for at least  months following CC- discontinuation, even\n                  if he has undergone a successful vasectomy.\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          . Subject has a significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study.\n\n          . Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study.\n\n          . Subject has any condition that confounds the ability to interpret data from the study.\n\n          . Subject has non- or oligosecretory multiple myeloma.\n\n          . Subject has plasma cell leukemia or active leptomeningeal myelomatosis.\n\n          . Subject has documented, systemic light chain amyloidosis or Polyneuropathy,\n             Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS)\n             Syndrome.\n\n          . Subject has immunoglobulin class M (IgM) myeloma.\n\n          . Subject has a history of allogeneic bone marrow transplantation.\n\n          . Subject is undergoing dialysis.\n\n         . Subjects with peripheral neuropathy ? Grade .\n\n         . Subjects with gastrointestinal disease that may significantly alter the absorption of\n             CC-.\n\n         . Subject has impaired cardiac function or clinically significant cardiac disease,\n             including any of the following:\n\n               -  LVEF < % as determined by ECHO or MUGA scan at Screening.\n\n               -  Complete left bundle branch, bifascicular block or other clinically significant\n                  abnormal electrocardiographic (ECG) finding at Screening.\n\n               -  A prolongation of QT interval on Screening ECG; a history of or current risk\n                  factors for Torsades de Pointe; and concurrent administration of medications that\n                  prolong the QT/QTc interval.\n\n               -  Congestive heart failure (New York Heart Association Class III or IV).\n\n               -  Myocardial infarction ? months prior to starting CC-.\n\n               -  Unstable or poorly controlled angina pectoris, including the Prinzmetal variant\n                  of angina pectoris.\n\n         . Concurrent administration of strong CYPA modulators.\n\n         . Subject had prior systemic myeloma treatment (approved or investigational) ? \n             half-lives or  weeks prior to starting CC-, whichever is shorter.\n\n         . Subject had major surgery ?  weeks prior to starting CC-.\n\n         . Subject is a pregnant or nursing female or intends to become pregnant during\n             participation in the study.\n\n         . Subject has known human immunodeficiency virus (HIV) infection.\n\n         . Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection.\n\n         . Subject has a history of concurrent second cancer requiring ongoing systemic\n             treatment.\n\n         . Subjects has a history of prior malignancy other than MM, unless the subject has been\n             free of disease for ? years except for the following noninvasive malignancies treated\n             with curative intent:\n\n         . Subject has known or suspected hypersensitivity to the excipients contained in the\n             formulation of CC- or dexamethasone.\n\n         . Subject has undergone either of the following within  days of initiating CC-:\n\n               -  Plasmapheresis.\n\n               -  Radiation therapy other than local therapy for symptomatic relief of MM\n                  associated bone lesions.\n\n         . Subject has received immunosuppressive medication within  days prior to the first\n             dose of CC-.
Inclusion criteria :\n\n        I . Males or females enrolled in Phase  or Phase  studies of SAR or SAR as\n        monotherapy or in combination with other regimens who have complete data collection for the\n        primary endpoint(s) of the parental study or who are being treated beyond the parental\n        study cut-off and meet all the criteria to continue to be treated per the parental\n        protocol.\n\n        I . All sexually active subjects (male and female) must agree to continue to use accepted\n        methods of barrier contraception (ie, condoms) during the course of the study and for \n        months after discontinuation of study treatment. For women of childbearing potential and\n        for men who can father a child, a second method of contraception in addition to a barrier\n        method is recommended. Hormonal contraception should be avoided in subjects taking\n        SAR due to possible drug-drug interaction.\n\n        I . Female subjects of childbearing potential must have a negative pregnancy test at\n        baseline. Females of childbearing potential are defined as sexually mature women without\n        prior hysterectomy or who have had any evidence of menses in the past  months. However,\n        women who have been amenorrheic for  or more months are still considered to be of\n        childbearing potential if the amenorrhea is possibly due to other causes, including prior\n        chemotherapy, anti-estrogens, or ovarian suppression\n\n        Exclusion criteria:\n\n        E . The subject discontinued the parental study due to toxicity\n\n        E . Ongoing Grade  or higher Adverse Event (AE)\n\n        E . Ongoing Serious Adverse Event (SAE)\n\n        E . Subjects with ongoing dose interruption for any reason unless the subject fulfills\n        the criteria in the parental protocol for restarting IMP. In such case subject will start\n        the treatment-extension study on Day  of the initiation period\n\n        E . The subject has any of the following laboratory values ? Common Terminology of\n        Adverse Events (CTCAE) Grade \n\n          -  Absolute neutrophil count (ANC),\n\n          -  Platelet count,\n\n          -  Hemoglobin,\n\n          -  Bilirubin,\n\n          -  Serum creatinine or calculated creatinine clearance,\n\n          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST),\n\n          -  Fasting plasma glucose (FPG),\n\n          -  Prothrombin time/international normalized ratio (PT/INR) and activated partial\n             thromboplastin time (aPTT)\n\n        E . The subject has a baseline corrected QT interval (QTc) > msec or if a subject has\n        had a QTc interval increase of ?  msec from parental protocol baseline to an absolute\n        value of >  msec\n\n        E . The subject has a known allergy or hypersensitivity to components of the study\n        treatment formulation(s)\n\n        E . The subject is pregnant or breastfeeding\n\n        The above information is not intended to contain all considerations relevant to a patient's\n        potential participation in a clinical trial.
Subject must not be pregnant or plan to conceive a child.
Subject has no clinically significant co-morbidities (i.e. chronic illnesses existing simultaneously with and usually independent of breast cancer) that affect life expectancy. Subject has given written informed consent
Subject who the investigator considers that chemotherapy is not indicated.
Subject must have either:
Subject has a positive serum Yo antibody
Subject has hematopoietic failure at baseline as defined by one of the following:
If the subject received at least  cycles of systemic therapy and no measurable tumor reduction compared to the previous scan is observed, such subject can be enrolled
For patients in Arm A, if the diagnostic pathology of the biopsy specimen is not consistent with recurrent glioblastoma (for example, only reactive gliosis or necrosis is detected), then the subject will be taken off study and be replaced with another subject that meets the inclusion criteria and is eligible for surgical resection
Subject is eligible for and plans to undergo ASCT
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          . Subject has an eligible disease:\n\n               -  Primary Acute myeloid leukemia (AML) induction failure: no Complete Remission\n                  (CR) after  or more induction attempts or\n\n               -  Relapsed AML: not in CR after  or more cycles of standard re-induction\n                  chemotherapy\n\n                    -  For relapsed subjects >  years of age, the  cycle of standard\n                       re-induction chemotherapy is not required if either of the following\n                       criteria is met:\n\n                    -  relapse within  months of last chemotherapy\n\n                    -  blast count <% within  days of starting this protocol therapy or\n\n               -  Secondary AML (MDS transformation or treatment related):\n\n             or\n\n              AML relapsed >  months after transplant Subjects with prior central nervous system\n             (CNS) involvement are eligible provided that it has been treated and Cerebrospinal\n             fluid (CSF) is clear for at least  weeks prior to Visit .\n\n          . Subject is ?  and ?  years of age at the time of signing the informed consent form\n             (ICF).\n\n          . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          . Subject is willing and able to adhere to the study schedule and other protocol\n             requirements.\n\n          . Karnofsky Performance Status > %.\n\n          . Ability to be off prednisone and other immunosuppressive drugs for at least  days\n             prior to the PNK- cell infusion.\n\n          . Female of childbearing potential (FCBP) must:\n\n             a. Have two negative pregnancy tests as verified by the Investigator prior to starting\n             study therapy. She must agree to ongoing pregnancy testing during the course of the\n             study, and after the end of study treatment. This applies even if the subject\n             practices true abstinence from heterosexual contact.\n\n          . Either commit to true abstinence from heterosexual contact or agree to use, and be\n             able to comply with, effective contraception without interruption,  days prior to\n             starting PNK-, during the study therapy (including dose interruptions), and for \n             days after discontinuation of study therapy. Male subjects must: a. Practice true\n             abstinence or agree to use a condom during sexual contact with a pregnant female or a\n             female of childbearing potential while participating in the study, during dose\n             interruptions and for at least  days following PNK- discontinuation, even if he\n             has undergone a successful vasectomy.\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          . Subject has any significant medical condition, laboratory abnormality, or known\n             psychiatric illness that would prevent the subject from participating in the study.\n\n          . Subject has any condition including the presence of laboratory abnormalities which\n             places the subject at unacceptable risk if he or she were to participate in the study.\n\n          . A subject has any condition that confounds the ability to interpret data from the\n             study.\n\n          . Subject has a body weight exceeding kg.\n\n          . Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or\n             alkaline phosphatase ? . x the upper limit of normal (ULN) at screening.\n\n          . Estimated glomerular filtration rate (eGFR) <  mL/min/. m at screening\n             calculated using the Modification of Diet in Renal Disease Study equation or history\n             of an abnormal eGFR <  and a decline of >  mL/min/. m below normal in the past\n             year.\n\n          . Subject has a bilirubin level >  mg/dL (unless subject has known Gilbert's disease)\n             at screening.\n\n          . Subject has had prior treatment with biologic antineoplastic agents no less than \n             days before PNK- infusion and at least  half lives. For agents that have known\n             Adverse Events (AEs) occurring beyond  days after administration (ie, monoclonal\n             antibodies), this period must be extended beyond the time during which acute AEs are\n             known to occur. An exception to this criteria is hydroxyurea which can be given\n             throughout the Screening/Baseline Period up to the time of the pre-conditioning\n             treatment.\n\n          . Subject has bi-phenotypic acute leukemia.\n\n         . Subject has had a transplant <  days prior to Visit  (Screening/Baseline visit).\n\n         . Subject has had treatment for graft-versus-host disease <  days prior to Visit \n             (Screening/Baseline visit).\n\n         . Subject is pregnant or breastfeeding.\n\n         . Subject has new or progressive pulmonary infiltrates or pleural effusion large enough\n             to be detected by chest x-ray or Computed tomography (CT) scan.\n\n         . Subject has active autoimmune disease other than controlled connective tissue disorder\n             or those who are not on active therapy.\n\n         . Subject is HIV positive.\n\n         . Subject has a history of malignancy except primary, secondary, or relapsed Acute\n             myeloid leukemia (AML), or excised and cured non-melanoma skin cancer, or cervical\n             carcinoma in situ that was surgically ablated more than  years prior to PNK-\n             infusion.\n\n         . Subject has a history of severe asthma and is presently on chronic medications or has\n             a history of other symptomatic pulmonary disease.\n\n         . Untreated chronic infection or treatment of any infection with systemic antibiotics\n             within  weeks prior to dosing with PNK-.\n\n         . Subject has any other organ dysfunction (CTCAE Version . Grade ) that will\n             interfere with the administration of the therapy according to this protocol.\n\n         . Subject has a resting left ventricular ejection fraction (LVEF) of < % obtained by\n             echocardiography or multigated acquisition scan (MUGA).
Other than the subject, Female of Childbearing Potential and males able to father a child should not handle CC- or touch the capsules, unless gloves are worn.
Subject has received previous systemic therapy for Hepatocellular carcinoma including sorafenib, chemotherapy and investigational agents . Subject has received any local anticancer therapy ?  weeks prior to baseline tumor evaluation . Subject has undergone major surgery within the last  weeks or minor surgery within the last  weeks prior to signing the Informed Consent Form or who have not recovered from surgery . Subject has received an investigational drug or therapy for disease other than Hepatocellular carcinoma within the last  weeks or  half-lives, whichever is shorter, prior to signing the Informed Consent Form . Subject has completed any radiation treatment less than  weeks prior to signing the Informed Consent Form . Subject has received the last dose of ?-interferon, ribavirin, sofobuvir and/or other antiviral therapies for Hepatitis C Virus (HCV) less than  weeks prior to signing the Informed Consent Form . Subject has any clinically significant bleeding, including bleeding from esophageal/gastric varices within ?  months of signing the informed consent form, which required transfusion, surgical procedure or hospitalization. Esophageal varices should be treated according to local standard practice (eg, ligation or banding and procedure completed ?  months prior to signing the informed consent form). See Inclusion Criterion  . Subjects requiring therapeutic anticoagulation with either warfarin or low molecular weight heparin. Low dose low molecular weight heparin for catheter maintenance are permitted . Subject has tumor invasion of stomach or duodenum . Subject has histologic proof of fibrolamellar carcinoma . Subjects with known symptomatic brain metastasis . Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) malabsorption ? National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, Version .) Grade , despite medical management, or any other significant GI disorder that could affect the absorption of either study drug . Subject has history of concurrent second cancers requiring active, ongoing systemic treatment. . Subject has a known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory) . Subject has peripheral neuropathy of at least NCI CTCAE Grade  . Subject has a history of persistent skin rash of at least NCI CTCAE Grade  . Subject has impaired cardiac function or clinically significant cardiac disease including any of the following:
Subjects with baseline blood pressure / mmHg are eligible but must have optimal medication for blood pressure management h. Troponin-T value more than the upper limit of normal or BNP greater than  pg/mL . Subject has acute or chronic active infectious disorders or uncontrolled nonmalignant illnesses whose control, in the opinion of the investigator, may be jeopardized by complications of this study therapy. Chronic hepatitis B and C virus (HBV and HCV) are excepted (ie, eligible for study); HBV requires antiviral therapy . Subject has undergone liver transplantation or other solid organ transplantation requiring immunosuppression . Subject is receiving chronic treatment with systemic corticosteroids or other potentially immunosuppressive agent. Intermittent topical or local injection of corticosteroids and oral/IV aldosterone or other mineralocorticoids is allowed . Subjects with history of non-healing wounds or ulcers, or bone fractures less than  months of a prior fracture . Subject is being treated with concomitant strong CYPA inducers such as St. John's Wort, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital. The use of concomitant strong CYPA inducers may decrease sorafenib plasma concentrations and must be avoided.
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          . Subject received at least  prior anti-myeloma regimens including a proteasome\n             inhibitor (PI) and an immunomodulatory agent or is double-refractory to a PI and an\n             immunomodulatory agent.\n\n               -  Induction, bone marrow transplant with or without maintenance therapy is\n                  considered one regimen.\n\n               -  Refractory is defined as disease that is nonresponsive on therapy, or progresses\n                  within  days of last therapy. Nonresponsive disease is defined as either\n                  failure to achieve minimal response or development of progressive disease while\n                  on therapy.\n\n               -  For subjects who received more than  regimen containing a PI their disease must\n                  be refractory to the most recent PI containing regimen.\n\n               -  For subjects who received more than  regimen containing a immunomodulatory agent\n                  their disease must be refractory to the most recent immunomodulatory agent\n                  containing regimen.\n\n          . All subjects must have failed Daratumumab (DARA) either as a single agent or in\n             combination on last Multiple myeloma (MM) therapy. Failure is defined as disease\n             progression(PD) on DARA either as a single agent or in combination.\n\n          . Subject has measurable disease defined as:\n\n               . M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis\n                  (uPEP): sPEP ? . g/dL or uPEP ?  mg/ hours) and/or\n\n               . Light chain MM without measurable disease in the serum or the urine: serum\n                  immunoglobulin free light chain ? mg/dL and abnormal serum immunoglobulin kappa\n                  lambda free light chain ratio\n\n          . Subject achieved a response (minimal response [MR] or better) to at least  prior\n             treatment regimen.\n\n          . Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of \n             or less.\n\n          . Subject's toxicities resulting from previous therapy (including peripheral neuropathy)\n             have resolved or stabilized to ? Grade .\n\n          . Subject is at least  years of age the time of signing the informed consent form\n             (ICF).\n\n          . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          . Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements.\n\n         . Females of childbearing potential (FCBP) must:\n\n             a. Have  negative pregnancy tests as verified by the investigator prior to starting\n             study treatment. This applies even if the subject practices true abstinence from\n             heterosexual contact.\n\n             i. Negative serum pregnancy test at screening ii. Negative serum or urine pregnancy\n             test (investigator's discretion) within  hours prior to starting study treatment\n             (Cycle , Day ), and before beginning each subsequent cycle of treatment, and after\n             end of study treatment.\n\n             b. Either practice true abstinence from heterosexual contact (which must be reviewed\n             on a monthly basis and source documented) or agree to use, and be able to comply with,\n             effective contraception without interruption (eg, oral, inject able, or implantable\n             hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive\n             with spermicide; true abstinence; or vasectomized partner),  days prior to starting\n             study treatment, during the study therapy (including dose interruptions), and for at\n             least  days after discontinuation of study treatment.\n\n             c. Agree to abstain from breastfeeding during study participation and for at least \n             days after the last dose of Daratumumab (DARA) or Durvalumab (DURVA), whichever is\n             later.\n\n             d. Refrain from egg cell donation for at least  days after the final dose of DURVA\n             or DARA, whichever is later.\n\n         . Male subjects must:\n\n               . Either practice true abstinence (which must be reviewed on a monthly basis) or\n                  agree to use a condom during sexual contact with a pregnant female or a female of\n                  childbearing potential while participating in the study, during dose\n                  interruptions and for at least  days following study treatment discontinuation,\n                  even if he has undergone a successful vasectomy.\n\n               . Refrain from sperm donation for at least  days after the final dose of DURVA or\n                  DARA, whichever is later.\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          . Subject has had prior exposure to anti-CTLA-, anti-PD- (Programmed cell death-),\n             anti-PD-L (Programmed death-ligand ) Monoclonal antibody (mAbs), or cancer vaccines\n\n          . Subject has received autologous stem cell transplantation (ASCT) within  weeks\n             before the date of randomization.\n\n          . History of organ or allogeneic stem cell transplantation\n\n          . Subject received any of the following within the last  days of initiating study\n             treatment:\n\n               . Plasmapheresis\n\n               . Major surgery (as defined by the investigator)\n\n               . Radiation therapy other than local therapy for myeloma associated bone lesions\n\n               . Use of any systemic anti-myeloma drug therapy (except for DARA either alone or in\n                  combination with other agents given with it)\n\n          . Subject received prior treatment with a monoclonal antibody within  half-lives of\n             initiating study treatment, other than DARA.\n\n          . Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for\n             cancer treatment. Note: Concurrent use of hormones for noncancer-related conditions\n             (eg, insulin for diabetes and hormone replacement therapy) is acceptable.\n\n          . Subject has any of the following laboratory abnormalities:\n\n               . Absolute neutrophil count (ANC) < ,/L\n\n               . Platelet count: < ,/L (it is not permissible to transfuse a subject to\n                  reach this level)\n\n               . Hemoglobin <  g/dL (< . mmol/L) (it is not permissible to transfuse a subject\n                  to reach this level)\n\n               . Creatinine clearance (CrCl) <  mL/min (calculated using the Cockcroft-Gault\n                  formula or directly calculated from the -hour urine collection method)\n\n               . Corrected serum calcium > . mg/dL (> . mmol/L)\n\n               . Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > . \n                  upper limit of normal (ULN)\n\n               . Serum total bilirubin > .  upper limit of normal (ULN) or > . mg/dL for\n                  subjects with documented Gilbert's syndrome\n\n          . Subject has clinical evidence of central nervous system (CNS) or pulmonary\n             leukostasis, disseminated intravascular coagulation, or CNS MM\n\n          . Subject has known chronic obstructive pulmonary disease (COPD) with a forced\n             expiratory volume in  second (FEV) < % of predicted normal. Note that forced\n             expiratory testing (FEV) is required for subjects suspected of having COPD and\n             subjects must be excluded if FEV is < % of predicted normal.\n\n         . Subject has known moderate or severe persistent asthma within the past  years or\n             uncontrolled asthma of any classification. Note that subjects who currently have\n             controlled intermittent asthma or controlled mild persistent asthma are allowed to\n             participate in the study.\n\n         . Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome\n             (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes),\n             or amyloidosis\n\n         . Subject has nonsecretory MM\n\n         . Subject has known allergy or hypersensitivity to study drug formulations\n\n         . Subject has active or prior documented autoimmune or inflammatory disorders (including\n             inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis, celiac\n             disease, irritable bowel disease, or other serious gastrointestinal chronic conditions\n             associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia\n             gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis, etc) within the\n             past  years prior to the start of treatment. The following are exceptions to this\n             criterion:\n\n               . Subjects with vitiligo or alopecia.\n\n               . Subjects with hypothyroidism (eg, following Hashimoto's disease) stable on\n                  hormone replacement.\n\n               . Psoriasis not requiring systemic treatment.\n\n         . Subject has history of primary immunodeficiency\n\n         . Subject is positive for human immunodeficiency virus (HIV-), chronic or active\n             hepatitis B or active hepatitis A or C.\n\n         . Subject has received live, attenuated vaccine within  days prior to the first dose\n             of DURVA (NOTE: Subjects, if enrolled, should not receive live vaccine during the\n             study and through  days after the last dose of DURVA)\n\n         . Subject is currently using or has used immunosuppressive medication within  days\n             prior to the first study dose of study treatment. The following are exceptions to this\n             criterion:\n\n               . Intranasal, topical, inhaled, or local steroid injections (eg, intra-articular\n                  injection).\n\n               . Systemic corticosteroids at physiologic doses not to exceed  mg/day of\n                  prednisone or equivalent.\n\n               . Steroids as premedication for hypersensitivity reactions (eg, infusion-related\n                  reactions, computed tomography [CT] scan premedication).\n\n         . Subject has any one of the following:\n\n               . Clinically significant abnormal Electrocardiogram (ECG) finding at screening\n\n               . Congestive heart failure (New York Heart Association Class III or IV)\n\n               . Myocardial infarction within  months prior to starting study treatment\n\n               . Unstable or poorly controlled angina pectoris, including Prinzmetal variant\n                  angina pectoris\n\n         . Subject has prior history of malignancies, other than MM, unless the subject has been\n             free of the disease for ?  years with the exception of the following noninvasive\n             malignancies:\n\n               . Basal cell carcinoma of the skin\n\n               . Squamous cell carcinoma of the skin\n\n               . Carcinoma in situ of the cervix\n\n               . Carcinoma in situ of the breast\n\n               . Incidental histologic finding of prostate cancer (Ta or Tb using the TNM\n                  [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is\n                  curative\n\n         . Subject is a female who is pregnant, nursing, or breastfeeding, or who intends to\n             become pregnant during the participation in the study.\n\n         . Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study\n\n         . Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study\n\n         . Subject has any condition that confounds the ability to interpret data from the study
Subject is not expected to show a therapeutic response to existing available treatment.
Subject with prior history of thrombotic microangiopathy or HUS within  months prior to enrollment
Subject with an infusion pump or any implantable neurostimulator device
Subject has documented history of allergic response to titanium or silicone
Inclusion Criteria:\n\n        Subjects shall be screened according to the following inclusion criteria. An answer of \no\\n        to any inclusion criterion disqualifies a subject from participating in this study.\n\n          -  Patients age: >  years\n\n          -  Subject has documented diagnosis of Barrett's esophagus, maximum endoscopic length of\n             no more than CM (i.e. no more than cm of circumferential extent and no more than\n             cm of tongues) containing HGD/EC as follows:\n\n          -  HGD or EC documented on biopsy within previous  months from enrollment\n\n          -  Histology slides reviewed at central pathology service for ERADICATE Trial confirm\n             HGD/EC.\n\n          -  Endoscopically visible lesion/area/pattern in a patient with HGD/EC either by high\n             definition white light endoscopy, narrow band imaging, confocal laser endomicroscopy,\n             or another enhanced imaging tool.\n\n          -  Ability to take oral proton pump inhibitor\n\n          -  For female subjects of childbearing potential, a negative urine pregnancy test within\n              weeks of enrollment and any subsequent endoscopy encounter\n\n          -  Subject is eligible for treatment and follow-up endoscopy and biopsy as required by\n             the investigational plan\n\n          -  Ability to discontinue aspirin/NSAIDs/Clopidogrel  days before and after all ablation\n             procedures\n\n          -  Ability of provide written, informed consent and understands the responsibilities of\n             trial participation NOTE: At the Kansas City Veterans Hospital, participants must be\n             eligible for care at the VA in order to be enrolled. Other sites listed are able to\n             enroll non-veterans.\n\n        Exclusion Criteria:\n\n        Subjects shall be screened according to the following exclusion criteria. An answer of\n        \yes\ to any exclusion criterion disqualifies a subject from participating in this study.\n\n          -  Extent of BE >CM\n\n          -  The subject is pregnant or planning a pregnancy during the study period ( months\n             after treatment)\n\n          -  Esophageal stricture preventing passage of endoscope or catheter\n\n          -  Active erosive esophagitis\n\n          -  History of malignancy of the esophagus, esophageal varices or coagulopathy\n\n          -  Prior radiation therapy to the esophagus, except head and neck region radiation\n             therapy.\n\n          -  Any previous ablation therapy within the esophagus (photodynamic therapy, multipolar\n             electrocoagulation, argon plasma coagulation, laser treatment, or other)\n\n          -  Any previous EMR in the esophagus\n\n          -  Any previous esophageal surgery, including fundoplication\n\n          -  Evidence of esophageal varices during treatment endoscopy\n\n          -  Subject has a life-expectancy of less than two years due to an underlying medical\n             condition\n\n          -  Subject has a known history of unresolved drug or alcohol dependency that would limit\n             ability to comprehend or follow instructions related to informed consent,\n             post-treatment instructions, or follow-up guidelines\n\n          -  Subject has an implantable pacing device (examples: Implantable cardiac defibrillator,\n             neurostimulator, cardiac pacemaker) and has not received clearance for enrollment in\n             this study by specialist responsible for the pacing device\n\n          -  The subject is currently enrolled in an investigational drug or device trial that\n             clinically interferes with the ERADICATE trial.\n\n          -  Subject suffers from psychiatric or other illness deemed by the investigator as an\n             inability to comply with protocol
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          . Subject is ?  years of age at the time of signing the ICF\n\n          . Subject has primary (ie, de novo) or secondary (progression of MDS or\n             myeloproliferative neoplasms ([MPN], or therapy-related) AML according to WHO\n             classification (Appendix B)\n\n          . Subject has received second- or third-line of AML therapy (see Appendix G for the\n             definition of prior AML line; note that, for subjects having AML secondary to prior\n             higher risk [Intermediate- or High risk according to the International Prognostic\n             Scoring System] MDS treated with a hypomethylating agent [eg, azacitidine or\n             decitabine], the hypomethylating therapy can be counted as a line if there is disease\n             progression to AML during or shortly [eg, within  days] after the hypomethylating\n             therapy.)\n\n          . Subject has the following disease status:\n\n               . Refractory to or relapsed after second- or third-line of intensive therapy for\n                  AML (eg, the \ + \ regimen):\n\n                  at least % leukemic blasts in bone marrow (the minimum number of treatment\n                  cycles of the intensive therapy is per the investigator's discretion); or\n\n               . Refractory to or relapsed after second- or third-line low-intensity AML therapy\n                  (eg, LDAC, azacitidine or decitabine):\n\n             at least % leukemic blasts in bone marrow after at least  treatment cycles\n\n          . Subject is eligible for and willing to receive the pre-selected CCR treatment option,\n             according to the investigator's assessment (Note: Subjects with degenerative and toxic\n             encephalopathies, especially after the use of methotrexate or treatment with ionizing\n             radiation, should not receive cytarabine.)\n\n          . Subject has Eastern Cooperative Oncology Group (ECOG) performance status of ,  or \n             (Appendix D)\n\n          . Subject has IDH gene mutations tested centrally (using the \investigational use\n             only\PCR assay, Abbott RealTime IDH) in samples of bone marrow aspirate and\n             peripheral blood, and confirmed positive in bone marrow aspirate and/or peripheral\n             blood. (Note: in the event that the central laboratory result is delayed and precludes\n             acute clinical management of a subject who has confirmed IDH gene mutation by local\n             evaluation, the subject may be eligible for randomization with approval by the Medical\n             Monitor.)\n\n          . Subject has adequate organ function defined as:\n\n               -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT)\n                  and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ? \n                  x upper limit of normal (ULN), unless considered due to leukemic organ\n                  involvement, following review by the Medical Monitor; and\n\n               -  Serum total bilirubin ? . x ULN, unless considered due to Gilbert's syndrome\n                  (eg, a gene mutation in UGTA) or leukemic organ involvement, following review\n                  by the Medical Monitor; and\n\n               -  Creatinine clearance >  mL/min based on the Modification of Diet in Renal\n                  Disease (MDRD) glomerular filtration rate (GFR):\n\n             GFR (mL/min/. m) =   (serum creatinine)-.  (Age)-.  (. if\n             female)  (. if African American)\n\n          . Females of childbearing potential (FCBP)* may participate, providing they meet the\n             following conditions:\n\n               -  Agree to practice true abstinence from sexual intercourse or to use highly\n                  effective contraceptive methods (eg, combined [containing estrogen and\n                  progestogen] or progestogen-only associated with inhibition of ovulation, oral,\n                  injectable, intravaginal, patch, or implantable hormonal contraceptive; bilateral\n                  tubal occlusion; intra-uterine device; intrauterine hormone-releasing system; or\n                  male partner sterilization [note that vasectomized partner is a highly effective\n                  birth control method provided that partner is the sole sexual partner of the FCBP\n                  trial participant and that the vasectomized partner has received medical\n                  assessment of the surgical success]) at screening and throughout the study, and\n                  for  months following the last study treatment ( months following the last dose\n                  of cytarabine); and\n\n               -  Have a negative serum ?-subunit of human chorionic gonadotropin (?-hCG) pregnancy\n                  test (sensitivity of at least  mIU/mL) at screening; and\n\n               -  Have a negative serum or urine (investigator's discretion under local\n                  regulations) ?-hCG pregnancy test (sensitivity of at least  mIU/mL) within \n                  hours prior to the start of study treatment in the Treatment Phase (note that the\n                  screening serum pregnancy test can be used as the test prior to the start of\n                  study treatment in the Treatment Phase if it is performed within the -hour\n                  timeframe).\n\n         . Male subjects must agree to practice true abstinence from sexual intercourse or to the\n             use of highly effective contraceptive methods (as described above) with non-pregnant\n             female partners of childbearing potential at screening and throughout the course of\n             the study, and should avoid conception with their partners during the course of the\n             study and for  months following the last study treatment ( months following the last\n             dose of cytarabine;  months following the last dose of azacitidine in Canada)\n\n         . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted\n\n         . Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          . Subject is suspected or proven to have acute promyelocytic leukemia based on\n             morphology, immunophenotype, molecular assay, or karyotype\n\n          . Subject has AML secondary to chronic myelogenous leukemia\n\n          . Subject has received a targeted agent against an IDH mutation\n\n          . Subject has received systemic anticancer therapy or radiotherapy <  days prior to\n             the start of study treatment. Note that hydroxyurea is allowed prior to the start of\n             study treatment for the control of leukocytosis (however, hydroxyurea should not be\n             given within  hours prior to and after administration of azacitidine).\n\n          . Subject has received non-cytotoxic or investigational agents <  days or \n             half-lives, whichever is longer, prior to the start of study treatment\n\n          . Subject has undergone HSCT within  days prior to the start of study treatment, or on\n             immunosuppressive therapy post HSCT at the time of screening, or with clinically\n             significant graft-versus-host disease (GVHD). The use of a stable dose of oral steroid\n             post-HSCT and/or topical steroids for ongoing skin GVHD is permitted.\n\n          . Subject has persistent, clinically significant non-hematologic toxicities from prior\n             therapies\n\n          . Subject has or is suspected of having central nervous system (CNS) leukemia.\n             Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is\n             suspected during screening.\n\n          . Subject has active uncontrolled systemic fungal, bacterial, or viral infection\n             (defined as ongoing signs/symptoms related to the infection without improvement\n             despite appropriate antibiotics, antiviral therapy, and/or other treatment)\n\n         . Subject has immediately life-threatening, severe complications of leukemia such as\n             uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated\n             intravascular coagulation\n\n         . Subject has significant active cardiac disease within  months prior to the start of\n             study treatment, including New York Heart Association (NYHA) class III or IV\n             congestive heart failure (Appendix E); acute coronary syndrome (ACS); and/or stroke;\n             or left ventricular ejection fraction (LVEF) < % by echocardiogram (ECHO) or\n             multi-gated acquisition (MUGA) scan obtained within  days prior to the start of\n             study treatment\n\n         . Subject has prior history of malignancy, other than MDS, MPN or AML, unless the\n             subject has been free of the disease for ?  year prior to the start of study\n             treatment.\n\n             However, subjects with the following history/concurrent conditions are allowed:\n\n               -  Basal or squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histologic finding of prostate cancer (Ta or Tb using the tumor,\n                  node, metastasis clinical staging system)\n\n         . Subject is known seropositive or active infection with human immunodeficiency virus\n             (HIV), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)\n\n         . Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other\n             conditions that limit the ingestion or gastrointestinal absorption of drugs\n             administered orally\n\n         . Subjects has uncontrolled hypertension (systolic blood pressure [BP] >  mmHg or\n             diastolic BP >  mmHg)\n\n         . Subject is a pregnant or lactating female\n\n         . Subject has known or suspected to have hypersensitivity to any of the components of\n             study treatment\n\n         . Subject is taking those medications (listed in Section .) that are known to prolong\n             QT interval unless the subject can be transferred to other medications at least \n             half-lives prior to the start of study treatment\n\n         . Subject has QTc interval (ie, Fridericia's correction [QTcF]) ?  ms or other\n             factors that increase the risk of QT prolongation or arrhythmic events (eg, heart\n             failure, hypokalemia, family history of long QT interval syndrome) at screening\n\n         . Subject is taking the following sensitive CYP substrate medications that have a narrow\n             therapeutic range are excluded from the study unless the subject can be transferred to\n             other medications at least  half-lives prior to the start of study treatment:\n             paclitaxel and docetaxel (CYPC), phenytoin (CYPC), S-mephenytoin (CYPC),\n             thioridazine (CYPD), theophylline, and tizanidine (CYPA)\n\n         . Subject is taking the breast cancer resistance protein (BCRP) transporter-sensitive\n             substrate rosuvastatin should be excluded from the study unless the subject can be\n             transferred to other medications at least  half-lives prior to the start of study\n             treatment\n\n         . Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study\n\n         . Subject has any condition including the presence of laboratory abnormalities, which\n             places the subject at unacceptable risk if he/she were to participate in the study\n\n         . Subject has any condition that confounds the ability to interpret data from the study
If a subject is receiving allopurinol/cimetidine/antivirals they must be discontinued prior to starting this protocol
Other than the subject, FCBP and males should not handle the IP or touch the capsules, unless gloves are worn.
Subject carries a diagnosis of active hepatitis B or C
Subject needs heart transplantation.
Subject has concomitant active second malignancies unless remission was achieved at least  years prior to study entry and subject is no longer on therapy for the malignancy.
The presence of any of the following will exclude a subject from enrollment:
Subject has a known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications.
Subject has not received fosbretabulin treatment in the study OXs
Subject has received either:
Subjects with biliary obstruction for whom a biliary drain or stent has been placed are eligible, provided that the drain or stent has been in place for at least  days prior to the first dose of Tivantinib, and the subject's liver function has stabilized as defined by  measurements at least  days apart that put the subject in the same hepatic impairment group
Inclusion Criteria:\n\n          -  Subject must currently be participating in an Astellas sponsored linsitinib trial that\n             has ended with respect to the overall study analysis.\n\n          -  Subject must not have met criteria for discontinuation or have progressed on the\n             current linsitinib study in which they are participating.\n\n          -  Subject must be deriving benefit from continued treatment.
Key Inclusion Criteria:\n\n        Male or female age ?  years with histologically confirmed diagnosis of melanoma and\n        unresected stage IIIB, IIIC, IVMa, IVMb, or IVMc regardless of prior line of therapy.\n        Subject is candidate for intralesional therapy administration into cutaneous, subcutaneous,\n        or nodal disease and must also have measurable disease, serum lactate dehydrogenase ? . x\n        upper limit of normal, and Eastern Cooperative Oncology Group (ECOG) performance status of\n         or , and adequate hematologic, hepatic, and renal organ function.\n\n        Key Exclusion Criteria:\n\n        Subject must not have clinically active cerebral metastases, greater than  visceral\n        metastases (this does not include lung metastases or any nodal metastases associated with\n        visceral organs) or any bone metastases melanoma, primary ocular or mucosal melanoma,\n        history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis,\n        or symptomatic autoimmune disease, or evidence of immunosuppression for any reason. Subject\n        known to have acute or chronic active hepatitis B or hepatitis C infection, or human\n        immunodeficiency virus infection will also be excluded. Subject who has active herpetic\n        skin lesions or prior complications of herpes simplex virus type  ( HSV-) infection (eg,\n        herpetic keratitis or encephalitis), and/or requires intermittent or chronic systemic\n        (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than\n        intermittent topical use will also be excuded. Subject must not have received previous\n        treatment with talimogene laherparepvec.
Has the subject elected not to undergo treatment with the Gliadel wafer?
Does the subject have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery?
The subject has had another active malignancy within the past  years except for any cancer in situ that the Principal Investigator considers to be cured. Questions regarding the inclusion of individual subject should be directed to the Medical Monitor.
PART II: Oncology participants must have histologically or cytologically diagnosed malignancy; ideally the subject has completed treatment within  months to a year and cancer is stable
Subject has received rifampin within  days prior to first dose of ABT-
The subject has a history of immunologic reaction to any Immunoglobulin G (IgG) containing agent.
Subject has a confirmed diagnosis of HbSS, HbSC, HbS?+thal, or HbS?thal
Subject requires hospitalization
Subject had a painful crisis requiring hospitalization within the preceding  days or has experienced >  hospitalizations for VOC in the prior  months
Subject is hospitalized for a condition other than VOC
Subject has complications related to SCD
Subject has completed a prior study utilizing ABT- or ln ABT- (ABT i) and the Investigator believes that continued treatment with ABT- is in the best interest of the subject.
subject elected not to undergo treatment with Gliadel wafer
The subject must have received intravenous fluid resuscitation
Subject has sustained extensive third-degree burns
Subject must be participating in an Astellas-sponsored ASP study which has completed, at a minimum, the primary analysis or have completed the individual study evaluation period requirements. Subject must not have met any discontinuation criteria in the parent study.
Subject who developed persistent intolerable toxicity to ASP treatment in the parent study.
Inclusion Criteria: -\n\n        Subject must have either  Relapsed or refractory Chronic Lymphocytic Leukemia/Small\n        Lymphocytic Lymphoma (for Waves  or )\n\n          -  Subject has evaluable disease and requires treatment in the opinion of the\n             investigator.\n\n          -  Subject must have relapsed following or be refractory to ?  standard treatments such\n             as fludarabine based regimens (F, FC, FR, FCR), alkylator (chlorambucil, bendamustine)\n             based regimens, or Bruton's Tyrosine Kinase inhibitor (Ibrutinib).\n\n        Or\n\n         Relapsed or refractory indolent Non-Hodgkin Lymphoma or aggressive Non-Hodgkin Lymphoma\n        (for Waves , , or , unless otherwise indicated)\n\n          -  Subject must have histologically documented diagnosis of a Follicular Lymphoma or\n             Marginal Zone Lymphoma.\n\n          -  Subject must have histologically documented diagnosis of a Diffuse Large B-cell\n             Lymphoma (excluding Richter's Transformation), Non-cutaneous T-Cell Lymphoma, or\n             Mantle Cell Lymphoma (MCL) (MCL Wave  only)\n\n          -  Subject has evaluable disease and requires treatment in the opinion of the\n             investigator.\n\n          -  Subject must have relapsed following or be refractory to ?  standard treatments such\n             as R-CHOP, R-CVP, bendamustine, lenalidomide-rituximab, or fludarabine-based regimens.\n\n               -  Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of\n                  less than or equal to .\n\n               -  Subject must have adequate bone marrow independent of growth factor support per\n                  local laboratory reference range at Screening.\n\n               -  Subject must have adequate coagulation, renal, and hepatic function, per\n                  laboratory reference range at Screening.\n\n               -  NHL subjects who have a history of an autologous stem cell transplant (e.g., bone\n                  marrow) must be >  months post-transplant (prior to the first dose of study\n                  drug) and must not require any growth factor support.\n\n        Exclusion Criteria:\n\n          -  Subject has been previously treated with a Bcl- or PIK inhibitor.\n\n          -  Subject is a candidate to receive another second-line therapy approved for usage by\n             the local Health Authority.\n\n          -  Subject is appropriate for a stem cell transplant or has undergone an allogeneic stem\n             cell transplant.\n\n          -  Subject has received any of the following within  days or  drug half-lives\n             (whichever is shortest) prior to the first dose of duvelisib or venetoclax, or has not\n             recovered to less than Grade  clinically significant adverse effect(s)/toxicity(s) of\n             the previous therapy:\n\n               -  Any anti-cancer therapy including chemotherapy or radiotherapy;\n\n               -  Investigational therapy, including targeted small molecule agents.\n\n          -  Subject has received biologic agents (e.g., monoclonal antibodies) for anti-neoplastic\n             treatment within  days prior to first dose of duvelisib or venetoclax.\n\n          -  Subject has received live or live attenuated vaccines within  weeks prior to first\n             dose of duvelisib or venetoclax.\n\n          -  Subject has received the following within  days prior to the first dose of duvelisib\n             or venetoclax:\n\n               -  Steroid therapy for anti-neoplastic treatment;\n\n               -  Strong and Moderate CYPA inhibitors;\n\n               -  Strong and Moderate CYPA inducers;\n\n               -  Chronic immunosuppressants, other than corticosteroids given at daily dose < \n                  mg prednisone equivalent for ITP or AIHA.
IC from the subject or assent from the subject and consent from a parent or guardian, if the subject is <  years of age
Subject is anticipated to need washed or volume reduced PLT during the course of this study
Subject is able to continue on the treatment regimen that the subject was receiving in the prior study. If in the investigator's assessment, a change is needed to the subject's regimen (e.g., dose change in Androgen deprivation therapy (ADT) or dropping of a combination therapy) approval from a medical monitor is required prior to enrollment.
Subject met any of the discontinuation criteria or whose cancer progressed on the current enzalutamide clinical study in which subject is enrolling from.
Subject requires treatment with or plans to use either of the following:
Subject understands and signs the Informed Consent
Subject agrees to return device to Mentor if device is explanted
Subject is pregnant at time of enrollment
EXCLUSION - STUDY : Under the circumstance that a subject develops CIPN during study , the subject will be withdrawn from the study but may be asked to participate in study 
The subject does not have a surgical indication for pancreatectomy
SUBJECT: Unable to travel to National Institute of Health (NIH) for the evaluations.
Subject must be clinically referred for a thyroidectomy for known or potential cancer
Subject is pregnant, planning to become pregnant, or is lactating. . Subject has a history of empyema. . Subject has a history of chylothorax. . Subject has an uncorrected coagulopathy. . Subject has a hypersensitivity to new or existing pleural catheter or it's components.
Subject has had a lobectomy or pneumonectomy on the side of the effusion. . Subject has undergone a previous attempt at ipsilateral pleurodesis which has failed.
Subject has evidence of fluid loculation such that attempts at pleurodesis are likely to be futile.
Subject has a mediastinal shift of ? cm toward the side of the effusion. . Subject is receiving concurrent intrapleural chemotherapy or radiation therapy to the ipsilateral chest.
The subject is undergoing one of the following reconstructive procedures that requires latissimus dorsi muscle harvest: a. post-mastectomy breast reconstruction procedure (either nipple or skin sparing) in which a female subject needs additional muscle coverage over an implant, but does not need additional skin (i.e., patient is a candidate for a pedicled latissimus dorsi muscle flap procedure); b. scalp reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage; c. upper extremity reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage; or, d. lower extremity reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage
The subject is diabetic
The subject has had prior back or axillary surgeries which could compromise the blood supply of the flap
The subject has a surgical indication for distal pancreatectomy
Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least  years.
Subject has MF with evidence of persistent disease despite ruxolitinib monotherapy treatment, consisting of:
Subject is receiving sodium-thiosulfate or amifostine therapy with chemotherapy.
Subject is using or is dependent on substances of abuse
Subject is in acute unstable condition
Subject cannot hold his/her breath for  seconds
Subject deemed unlikely to be able to comply with instructions during imaging
Subject weighs more than  pounds or otherwise cannot be safely fit into the imaging system
Institutionalized subject (prisoner or nursing home patient)
Ability to understand and carry out subject instructions
Subject with normal oral tissue
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          . Subject has eligible disease status:\n\n               . Newly diagnosed and are undergoing induction therapy prior to undergoing first\n                  Autologous stem cell transplant (ASCT) or\n\n               . Myeloma patients with prior relapse undergoing first ASCT. or\n\n               . Myeloma patients with relapsed disease after first ASCT who are undergoing second\n                  ASCT. Subjects must have achieved at least a partial response (PR) prior to\n                  proceeding to ASCT.\n\n          . Subject is >  and ?  years of age at the time of signing the informed consent form\n             (ICF).\n\n          . Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          . Subject is willing and able to adhere to the study schedule and other protocol\n             requirements.\n\n          . Performance status of Karnofsky performance status ? % or Eastern Cooperative\n             Oncology Group (ECOG) < \n\n          . Ability to be off immunosuppressive drugs for at least  days prior to the PNK-\n             cell infusion. Steroids at the equivalent of no more than  mg prednisone per day are\n             permissible.\n\n          . Be a candidate for ASCT based on institutional practices.\n\n          . Subjects must have autologous peripheral blood stem cell graft available in storage\n             for additional transplant in the event of engraftment failure.\n\n          . Female of childbearing potential (FCBP) must:\n\n               . Have two negative pregnancy tests as verified by the Investigator prior to\n                  starting study therapy. She must agree to ongoing pregnancy testing during the\n                  course of the study, and after the end of study treatment. This applies even if\n                  the subject practices true abstinence* from heterosexual contact.\n\n               . Either commit to true abstinence* from heterosexual contact (which must be\n                  reviewed at applicable study visits and source documented) or agree to use, and\n                  be able to comply with, effective contraception without interruption, during the\n                  study therapy (including dose interruptions), and for  days after\n                  discontinuation of PNK-.\n\n                  A female of childbearing potential (FCBP) is a female who:\n\n                  ) has achieved menarche at some point, ) has not undergone a hysterectomy or\n                  bilateral oophorectomy or ) has not been naturally postmenopausal (amenorrhea\n                  following cancer therapy does not rule out childbearing potential) for at least\n                   consecutive months (ie, has had menses at any time in the preceding \n                  consecutive months).\n\n         . Male subjects must:\n\n               . Practice true abstinence* (which must be reviewed at applicable study visits) or\n                  agree to use a condom during sexual contact while participating in the study,\n                  during dose interruptions and for at least  days following PNK-\n                  discontinuation, even if he has undergone a successful vasectomy. * True\n                  abstinence is acceptable when this is in line with the preferred and usual\n                  lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation,\n                  symptothermal, post ovulation methods] and withdrawal are not acceptable methods\n                  of contraception]).\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          . Subject has plasma cell leukemia.\n\n          . Subject has non-secretory myeloma.\n\n          . Subject has previously undergone allogeneic stem cell transplant.\n\n          . Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study.\n\n          . Subject has any condition including the presence of laboratory abnormalities which\n             places the subject at unacceptable risk if he or she were to participate in the study.\n\n          . Subject has any condition that confounds the ability to interpret data from the study.\n\n          . Subject has a body weight exceeding  kg.\n\n          . Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or\n             alkaline phosphatase ? . x the upper limit of normal (ULN) at screening.\n\n          . Estimated glomerular filtration rate (eGFR) <  mL/min/. m at screening\n             calculated using the Modification of Diet in Renal Disease Study equation.\n\n         . Subject has a bilirubin level >  mg/dL (unless subject has known Gilbert's disease)\n             at screening.\n\n         . Subject has had prior treatment with biologic antineoplastic agents no less than \n             days before PNK- infusion and at least  half-lives. For agents that have known AEs\n             occurring beyond  days after administration (ie, monoclonal antibodies), this period\n             must be extended beyond the time during which acute AEs are known to occur.\n\n         . Subject is pregnant or breastfeeding.\n\n         . Subject has new or progressive pulmonary infiltrates or pleural effusion large enough\n             to be detected by chest x-ray or computed tomography (CT) scan.\n\n         . Subject has active autoimmune disease other than controlled connective tissue disorder\n             or those who are not on active therapy.\n\n         . Subject has human immunodeficiency virus (HIV) are excluded due to increased risk of\n             lethal infections when treated with myeloablative chemotherapy.\n\n         . Subject has history of malignancy, other than multiple myeloma (MM), unless the\n             subject has been free of disease for >  years from the date of signing the ICF.\n             Exceptions include the following:\n\n               . Basal cell carcinoma of the skin\n\n               . Squamous cell carcinoma of the skin\n\n               . Carcinoma in situ of the cervix\n\n               . Carcinoma in situ of the breast\n\n               . Incidental histological finding of prostate cancer (TNM stage of Ta or Tb)\n\n         . Subject has a history of severe asthma and is presently on chronic medications or has\n             a history of other symptomatic pulmonary disease.\n\n         . Untreated chronic infection or treatment of any infection with systemic antibiotics\n             within  weeks prior to melphalan.\n\n         . Subject has any other organ dysfunction that will interfere with the administration of\n             the therapy according to this protocol.\n\n         . Subject has a resting left ventricular ejection fraction (LVEF) of < % obtained by\n             echocardiography or multigated acquisition scan (MUGA).\n\n         . Subject was treated with an investigational product no less than  days before\n             PNK- infusion. Subject must no longer be a participant in the previous\n             interventional study at the time of the PNK- infusion.
Subject consents to allow access to subject's diagnostic bone marrow aspirate or peripheral blood sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic test that is being developed in parallel with gilteritinib.
Subject is <  months from the start of the last cycle of consolidation and should have completed the recommended number of consolidations per local practice.
Subject's schedule permits compliance with all study procedures
Pregnant or breastfeeding - if the subject is female, the investigator will provide a urine pregnancy test at no cost to the subject; the subject will take the pregnancy test immediately before participating in this study
Subject enrolls into LCCC
FOCUS GROUP SUBJECT SELECTION
Inclusion Criteria:\n\n        Subjects who meet all of the following criteria may be enrolled in this Study:\n\n          . Subject is male or female, age  or older.\n\n          . Subject has undergone CT scan of the lung(s) that indicates one or more nodules or\n             lesions suspicious for lung cancer.\n\n          . Subject's pulmonary nodule or lesion is greater than mm. Size is determined by the\n             largest nodule or lesion dimension identified from CT imaging.\n\n          . Subject meets one or more of the following conditions:\n\n               -  indicated for a tissue biopsy\n\n               -  indicated for surgical resection of the lung\n\n          . Subject must be able to receive a ProLung Test\n\n               -  within  days of abnormal CT (Inclusion Criterion  & )\n\n               -  within  days prior to the tissue biopsy or surgical resection (Inclusion\n                  Criterion ).\n\n          . Subject is capable of understanding and agreeing to fulfill the requirements of this\n             Protocol.\n\n          . Subject has signed the IRB/IEC approved Informed Consent Form (\ICF\).\n\n        Exclusion Criteria\n\n        The following criteria will disqualify a subject from enrollment into this Study:\n\n          . Subject has an implanted electronic device in the chest.\n\n          . Subject receiving therapy for suspected chest infection such as fungal infection or\n             tuberculosis.\n\n          . Subject with diagnosed malignancy other than lung cancer, non-melanoma skin cancer or\n             any cancer in which the Principal Investigator does not suspect metastatic disease to\n             the lung, who has  or more suspicious pulmonary nodules.\n\n          . Subject has received an invasive medical or surgical procedure within the thoracic\n             cavity within  days prior to the ProLung Test or within the previous  days for a\n             bronchoscopic procedure.\n\n          . Subject presents with an anomalous physical or anatomical condition that precludes\n             ProLung Test measurement.\n\n          . Subject will have undergone unusually strenuous exercise within  hours.\n\n          . Subject who has significant systemic diseases such as uncontrolled diabetes, advanced\n             heart failure, or a recent myocardial infarction, or other medical condition such as\n             severe morbid obesity that in the judgment of the Principal Investigator would make\n             him/her unsuitable for the Study.
Inclusion Criteria:\n\n        Subjects who meet all of the following criteria may be enrolled in this Study:\n\n          . Subject is male or female, age  or older.\n\n          . Subject has undergone CT scan of the lung(s) that indicates one or more nodules or\n             lesions suspicious for lung cancer.\n\n          . Subject's pulmonary nodule or lesion is greater than mm. Size is determined by the\n             largest nodule or lesion dimension identified from CT imaging.\n\n          . Subject meets one or more of the following conditions:\n\n               -  indicated for a tissue biopsy\n\n               -  indicated for surgical resection of the lung\n\n          . Subject must be able to receive a ProLung Test\n\n               -  within  days of abnormal CT (Inclusion Criterion  & )\n\n               -  within  days prior to the tissue biopsy or surgical resection (Inclusion\n                  Criterion ).\n\n          . Subject is capable of understanding and agreeing to fulfill the requirements of this\n             Protocol.\n\n          . Subject has signed the IRB/IEC approved Informed Consent Form (\ICF\).\n\n        Exclusion Criteria\n\n        The following criteria will disqualify a subject from enrollment into this Study:\n\n          . Subject has an implanted electronic device in the chest.\n\n          . Subject receiving therapy for suspected chest infection such as fungal infection or\n             tuberculosis.\n\n          . Subject with diagnosed malignancy other than lung cancer, non-melanoma skin cancer or\n             any cancer in which the Principal Investigator does not suspect metastatic disease to\n             the lung, who has  or more suspicious pulmonary nodules.\n\n          . Subject has received an invasive medical or surgical procedure within the thoracic\n             cavity within  days prior to the ProLung Test or within the previous  days for a\n             bronchoscopic procedure.\n\n          . Subject presents with an anomalous physical or anatomical condition that precludes\n             ProLung Test measurement.\n\n          . Subject will have undergone unusually strenuous exercise within  hours.\n\n          . Subject who has significant systemic diseases such as uncontrolled diabetes, advanced\n             heart failure, or a recent myocardial infarction, or other medical condition such as\n             severe morbid obesity that in the judgment of the Principal Investigator would make\n             him/her unsuitable for the Study.
Investigator feels participation is not in the best interest of the subject.
Acuity of surgical needs: Subjects with acute neurologic compromise, symptoms of impending cerebral herniation, or other condition(s) necessitating urgent or emergent neurosurgical intervention to be planned within  hours not eligible. NOTE: If subject is enrolled on study, receives study medication and subsequently condition worsens such that urgent surgical intervention is felt to be in best interest of subject, best interest of subject should always take precedence over timing between study medication and surgery
Any subject for whom the investigator feels participation is not in the best interest of the subject.
Any subject for whom the investigator feels participation is not in the best interest of the subject.
In France, a subject will not be eligible when under legal protection.