ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C): Patients with serious medical or psychiatric illness that in the opinion of the primary investigator is likely to interfere with study participation may not be enrolled
ELIGIBILITY CRITERIA - PHASE II (ARM D): Patients with serious medical or psychiatric illness that in the opinion of the primary investigator is likely to interfere with study participation may not be enrolled
Other illness or condition, including laboratory abnormalities, which in the opinion of the Investigator would exclude the patient from participating in this study. This includes, but is not limited to, serious medical conditions or psychiatric illness likely to interfere with participation in the study.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patient with serious medical of psychiatric illness likely to interfere with participation on this clinical study
Participant has a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patient must not have serious medical or psychiatric illness likely to interfere with participation in this clinical study in the opinion of the investigator.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study, in the opinion of the investigator
Active, uncontrolled serious infection or medical or psychiatric illness, that in the investigator’s opinion is likely to interfere with participation in this clinical trial
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Active, uncontrolled, serious infection, or medical, or psychiatric illness likely to interfere with participation in this clinic trial
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
RANDOMIZED PHASE II (ARMS K AND L): Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious psychiatric illness or addiction likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
No serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Participant with a serious medical or psychiatric illness likely to interfere with participation in the study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Concomitant medical or psychiatric illness that is likely to interfere with a reasonably safe execution of the treatment plan
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study per the judgment of the treating physician
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Active, uncontrolled, serious infection or medical or psychiatric illness likely to interfere with participation in this clinic trial
Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
Subject has a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Subject or subject's partner is willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer.
The subject has a gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine
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
Subject has an active implantable or other electromagnetic device.
Subject must be able to swallow solid dosage forms.
Inclusion Criteria:\n\n Subjects must satisfy the following criteria to be enrolled in the study:\n\n 1. Subject is ?18 years of age at the time of signing the informed consent form (ICF)\n\n 2. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted\n\n 3. Subject is willing and able to adhere to the study visit schedule and other protocol\n requirements\n\n 4. 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 ?0.5 g/dL\n or uPEP\n\n ?200 mg/24 hours\n\n 5. All subjects must have received at least 2 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 6. All subjects must have received prior treatment with at least 2 consecutive cycles of\n a lenalidomide or pomalidomide-containing regimen\n\n 7. All subjects must have received prior treatment with at least 2 consecutive cycles of\n a proteasome inhibitor or a proteasome inhibitor-containing regimen\n\n 8. For Part 2 (Cohort C and Cohort D), all subjects must have received prior treatment\n with at least 2 consecutive cycles of an anti-CD38 therapy or an anti-CD38-containing\n regimen\n\n 9. All subjects must have documented disease progression on or within 60 days from the\n last dose of their last myeloma therapy\n\n 10. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2\n\n 11. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at\n some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has\n not been naturally postmenopausal (amenorrhea following cancer therapy does not rule\n out childbearing potential) for at least 24 consecutive months (ie, has not had menses\n at any time in the preceding 24 consecutive months) and must:\n\n 1. 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 2. 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 28\n days prior to starting investigational product, during the study therapy\n (including dose interruptions), and for 28 days after discontinuation of study\n therapy. Contraception requirements are detailed in Appendix D.\n\n 12. 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 90 days following the last dose of CC-220, 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 13. Males must agree to refrain from donating sperm while on CC-220, during dose\n interruptions and for at least 90 days following last dose of CC-220.\n\n 14. All subjects must agree to refrain from donating blood while on CC-220, during dose\n interruptions and for at least 28 days following the last dose of CC-220.\n\n 15. All male and female subjects must follow all requirements defined in the Pregnancy\n Prevention Program (v5.1).\n\n Exclusion Criteria:\n\n The presence of any of the following will exclude a subject from enrollment:\n\n 1. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n illness that would prevent the subject from participating in the study\n\n 2. 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 3. Subject has any condition that confounds the ability to interpret data from the study\n\n 4. Subject has nonsecretory or oligosecretory multiple myeloma\n\n 5. Subjects with Plasma Cell leukemia\n\n 6. Any of the following laboratory abnormalities\n\n - Absolute neutrophil count (ANC) <1,000/?L\n\n - Platelet count <75,000/?L Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)\n\n - Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)\n or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ?2.0\n x upper limit of normal (ULN)\n\n - Serum total bilirubin and alkaline phosphatase >1.5 x Upper Limit of Normal (ULN)\n\n - Subjects with serious renal impairment (24-hour creatinine clearance [CrCl] <50\n mL/min) or requiring dialysis would be excluded\n\n 7. Subjects with peripheral neuropathy ?Grade 2\n\n 8. Subjects with gastrointestinal disease that may significantly alter the absorption of\n CC-220\n\n 9. Subjects with a prior history of malignancies, other than MM, unless the subject has\n been free of the disease for ?5 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 T1a or T1b using the\n Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer\n that is curative\n\n 10. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide,\n pomalidomide or DEX\n\n 11. Subject has known or suspected hypersensitivity to the excipients contained in the\n formulation of CC-220 or DEX\n\n 12. Subject has received any of the following within the last 14 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 13. Subject has been treated with an investigational agent (ie, an agent not commercially\n available) within 28 days or 5 half-lives (whichever is longer) of initiating\n investigational product (IP)\n\n 14. 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 12 months prior to starting IP\n\n - Unstable or poorly controlled angina pectoris, including the Prinzmetal variant\n of angina pectoris\n\n 15. Subject has current or prior use of immunosuppressive medication within 14 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 10 mg/day of\n prednisone or equivalent\n\n - Steroids as premedication for hypersensitivity reactions (eg, computed tomography\n [CT] scan premedication)\n\n 16. Subject has taken a strong inhibitor or inducer of CYP3A4/5 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 17. Subject known to test positive for human immunodeficiency virus (HIV), chronic or\n active hepatitis B, or active hepatitis A or C\n\n 18. Subject is unable or unwilling to undergo protocol required thromboembolism\n prophylaxis\n\n 19. Subject is a female who is pregnant, nursing or breastfeeding
Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
Two appropriate CB units identified for the subject.
Subject has other conditions that in the opinion of the investigator would place the subject at increased risk for toxicity by participation in the study.
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 0, 1 or\n 2.\n\n - Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was\n at least 21 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 4 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 21 days prior to initiation of study drug administration.\n For drugs with a half-life greater than or equal to 21 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 7 days prior to the start\n of study drug administration.\n\n - Subject has completed any radiotherapy (including stereotactic radiosurgery) at least\n 2 weeks prior to study drug administration.\n\n - Subject's adverse events (excluding alopecia) from prior therapy have improved to\n grade 1 or baseline within 14 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 ? 50 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 ? 4 weeks after any blood transfusion.\n\n - Female subject must either:\n\n - Be of non-childbearing potential: Postmenopausal (defined as at least 1 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 6 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 6 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 6 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 6 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 6 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 6 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 6 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 6 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 1 measureable lesion per Response Evaluation Criteria in Solid\n Tumors (RECIST) 1.1. 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 2 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 ? 1 week between each determination) within 6\n weeks prior to study drug administration and a PSA value at the screening visit ?\n 2 ng/mL.\n\n - Subject consents to provide an available tumor specimen in a tissue block or unstained\n serial slides obtained within 56 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 < 45 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 21 days prior to start of study drug.\n\n - Subject requires or has received systemic steroid therapy or any other\n immunosuppressive therapy within 14 days prior to study drug administration. Subjects\n using a physiologic replacement dose of hydrocortisone or its equivalent (defined as\n up to 30 mg per day of hydrocortisone up to 10 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 4 weeks prior\n to start of study treatment and are not requiring immunosuppressive doses of systemic\n steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of prednisone or\n equivalent) for longer than 2 weeks.\n\n - Subject has an active autoimmune disease. Subjects with type 1 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 ? 3\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 ASP8374 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 28 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 14 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 6 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 28\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 3 or more surgeries/procedures in any one year to remove the lesions from their larynx; subjects must have evaluable disease either based on RECIST 1.1 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:
Subject in whom any major intraoperative bleeding incidences during the surgical procedure occurred (i.e., subject with assignment of an American College of Surgeons Advanced Trauma Life Support Hemorrhage Class of II, III, or IV Hemorrhage);
Platelets >= 50,000/uL; a subject will not be excluded because of pancytopenia related to disease
RETREATMENT WITH MODIFIED T-CELLS INCLUSION CRITERIA: Subject has modified T cell product available for release
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 2+FDR with T1D
Subject has received:
Subject must have been as fully resected as possible per the physician's judgment.
Subject has histologic or cytologic confirmation of metastatic NSCLC. Subjects must have a TPS score available as determined by an FDA approved test. Subject has stable disease or disease progression and is being treated with pembrolizumab therapy as standard of care by the Investigator.
The subject (or legally acceptable representative if applicable) provides written informed consent for the trial. The subject may also provide consent for future biomedical research. However the subject may participate in the main trial without participating in future biomedical research.
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 7 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 325 mg/day is permitted.\r\n* The subject received previous systemic chemotherapy with a cumulative dose of > 900 mg/m^2 of epirubicin or > 400 mg/m^2 of doxorubicin. \r\n* The subject has a significant bleeding disorder or vasculitis or had a grade >= 3 bleeding episode within 12 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 6 months prior to the first dose of trial treatment.\r\n* The subject experienced any grade 3 or 4 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 6 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 4.0, prior to initiating study treatment, despite antihypertensive intervention. CTCAE version 4.0 defines uncontrolled hypertension as grade > 2 hypertension; clinically, the patient continues to experience elevated blood pressure [systolic > 160 mmHg and/or diastolic > 100 mmHg] despite medications).\r\n* The subject has a history of gastrointestinal (GI) perforation or fistula within 6 months prior to the 1st 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 28 days prior to the first dose of study drug.
The subject must have experienced at least one of the following:
Subject is participating in any other therapeutic clinical study (observational or registry trials are allowed)
Subjects with any concomitant disease or condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
Subject weighs more than 450 pounds
Inclusion Criteria (All questions must be answered \YES\ in order for the subject to be\n considered for the study):\n\n 1. Is the subject a male or female between18 and 75 years of age inclusive who is able to\n provide informed consent?\n\n 2. Does the subject have histologically-confirmed diagnosis of CD20-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 3 lymphoma are not\n eligible.\n\n 3. Does the subject have an ECOG score of 0, 1 or 2?\n\n 4. Does the subject have an IPI score of at least 3?\n\n 5. Does the subject have an estimated life expectancy of at least 12 weeks?\n\n 6. Does the subject have adequate organ function as follows:\n\n 1. Hepatic: total bilirubin ?1.5 times upper limit of normal (ULN); alanine\n transaminase (ALT) and aspartate transaminase (AST) ?1.5 times ULN (<5 times ULN\n if liver involvement)\n\n 2. Renal: estimated GFR of >50 ml/min by Cockcroft- Gault equation\n\n 3. Bone marrow: platelets ?75 x 109/L, absolute neutrophil count (ANC) ?1.5 x 109/L,\n hemoglobin ?10 g/dL, unless there is bone marrow involvement\n\n 7. 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 3 months after discontinuation of\n study treatment? Women of childbearing potential must have a negative serum pregnancy\n test within 7 days prior to start of treatment.\n\n 8. Does the subject have a left ventricular ejection fraction ?50% by echocardiography or\n nuclear medicine multi-gated scan?\n\n 9. Is the subject able to swallow tablets?\n\n 10. Does the subject have adequate transportation to allow for required follow-up visits?\n\n 11. 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 1. Has the subject received treatment with an investigational drug within the last 30\n days?\n\n 2. Is the subject receiving, or has the subject received, any other radiation or systemic\n anticancer treatment for lymphoma?\n\n 3. Is the subject pregnant or breastfeeding?\n\n 4. Does the subject have known central nervous system (CNS) involvement?\n\n 5. Does the subject have any significant concomitant disorder, including active\n bacterial, fungal, or viral infection, incompatible with participation in the study?\n\n 6. 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 5 years, are eligible.\n\n 7. Is the subject unable to discontinue use of a concomitant medication that is a strong\n inducer or inhibitor of CYP3A4? (See Appendix A).\n\n 8. Does the subject have a family history of long QT syndrome, or a QTc interval >450\n (males) or 470 (females) at screening, a history of arrhythmias or a history of\n unexplained syncope?\n\n 9. Must the subject take any medication that can prolong the QT/QTc interval? (See\n Appendix C)\n\n 10. Does the subject have a history of severe allergic or anaphylactic reaction to\n monoclonal antibody therapy?\n\n 11. Does the subject have a confirmed diagnosis of progressive multifocal\n leukoencephalopathy?\n\n 12. Does the subject have a history of grade 2 or higher peripheral neuropathy?\n\n 13. Does the subject have any of the following cardiac disorders: uncontrolled\n hypertension, unstable angina, myocardial infarction within 8 weeks of Day1, NYHA\n Grade 2 or higher congestive heart failure, ventricular arrhythmia requiring\n medication within 1 year of Day 1, NYHA Grade 2 or higher peripheral vascular disease?\n\n 14. Has the subject received a live vaccine within 28 days of study Day 1?\n\n 15. Is the subject HIV positive?\n\n 16. Does the subject have evidence of chronic hepatitis C infection as indicated by\n antibody to HCV with positive HCV-RNA?\n\n 17. Does the subject have evidence of chronic hepatitis B infection as indicated by\n either:\n\n 1. HBsAg+ or\n\n 2. HBcAb+ with HBV-DNA+
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 30 days.
Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study
Inclusion Criteria:\n\n Disease Related\n\n 1. Subject has confirmed histologic or cytologic evidence of metastatic pancreatic cancer\n and has no prior treatment for metastatic pancreatic cancer.\n\n 2. Subject has measurable disease using Response Evaluation Criteria in Solid Tumors\n (RECIST) v 1.1.\n\n 3. Subject has a life expectancy of at least 3 months.\n\n 4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n\n Demographic\n\n 5. Males or females ? 18 years of age\n\n 6. Subject must be able to swallow capsules\n\n 7. Subject must have adequate venous access for intravenous (IV) infusion\n\n Laboratory\n\n 8. Subject has hemoglobin ? 9.0 g/dL at Screening\n\n 9. Subject has absolute neutrophil count (ANC) ? 1.5 x 109/L at Screening\n\n 10. Subject has platelet count ? 100 x 109/L at Screening\n\n 11. Subject has serum creatinine ? 1.5 times the upper limit of normal (ULN) at Screening.\n Subjects with serum creatinine levels > 1.5 times the ULN must have a 24-hour urine\n creatinine clearance ? 60 mL/min\n\n 12. Subject has serum bilirubin ? 1.5 times the ULN (except in subjects with Gilbert's\n Syndrome who must have serum bilirubin < 3.0 x ULN)\n\n 13. Subject has aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT;\n SGPT) ? 2.5 times the ULN (OR, AST and ALT ? 5 times the ULN in the presence of known\n liver metastases)\n\n 14. Subject has alkaline phosphatase ? 2.5 times the ULN (OR ? 5 times the ULN in the\n presence of known liver or bone metastases)\n\n 15. Subject has normal coagulation parameters (prothrombin time [PT] and/or international\n normalized ratio [INR], and partial thromboplastin time [PTT] within normal limits\n [<1.2 x ULN])\n\n 16. Subject has potassium concentration within normal range, or correctable with\n supplements.\n\n 17. Oxygen saturation by pulse oximetry ? 92% at rest.\n\n 18. For women of childbearing potential: Negative serum pregnancy test during screening\n and negative serum or urine pregnancy test at start of study therapy (Cycle1 Day 1).\n\n Reproductive\n\n 19. 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 30 days following\n the last dose of study drug.\n\n 20. Female subjects of non-childbearing potential defined as having amenorrhea for at\n least 24 consecutive months, a documented hysterectomy, or a documented bilateral\n oophorectomy)\n\n 21. 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 30 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 30 days following the last dose of study drug.\n\n Ethical\n\n 22. 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 23. Before any study-specific procedure, the appropriate written informed consent must be\n obtained\n\n Exclusion Criteria:\n\n Disease Related\n\n 1. Subject has primary brain tumors or clinical evidence of active brain metastasis\n\n 2. Subject has undergone major surgery within 4 weeks of the start of study treatment.\n Laparoscopy and central venous catheter placement are not considered major surgery\n\n Medications\n\n 3. Subject has a history of systemic corticosteroid use within 7 days before Day 1 of\n Cycle 1\n\n General\n\n 4. Subject has an active infection requiring parenteral or oral antibiotics within 2\n weeks before planned start of study therapy\n\n 5. Subject has uncontrolled diabetes as assessed by the investigator\n\n 6. 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 3 years\n before planned start of study therapy\n\n 7. Subject has an active infection of hepatitis B, hepatitis C or human immunodeficiency\n virus\n\n 8. Female subjects who are pregnant, planning a pregnancy or breast feeding during the\n study\n\n 9. 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 6\n months before planned start of study therapy or r myocardial infarction within one\n year before planned start of study therapy\n\n 10. Subject has a history of peripheral artery disease (e.g., claudication, Leo Buerger's\n disease).\n\n 11. Subject has a history of prior allogeneic bone marrow progenitor cell or solid organ\n transplantation.\n\n 12. Subject has known acute or chronic pancreatitis.\n\n 13. Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ?\n NCI CTCAE Grade 2, despite medical management.\n\n 14. Subject has any disorder that may interfere with drug absorption, distribution,\n metabolism, or excretion (including gastrointestinal surgery and bariatric surgery)\n\n 15. All acute toxic effects of any prior antitumor therapy resolved to Grade ? 1 before\n the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted],\n or neurotoxicity [Grade 1 or 2 permitted], or anemia [Grade 2 permitted])\n\n 16. 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 17. 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 18. 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 19. Subject has a history of hypersensitivity to RX-3117, gemcitabine, azacytidine\n cytosine arabinoside, paclitaxel, nab-paclitaxel, or their excipients.\n\n 20. Subject is unwilling or unable to comply with study requirements or planned\n unavailability for follow-up assessments.
Subject is HLA-A*02 positive and subject's tumor shows expression of the MAGE-A4 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
History/presence of arrhythmia (even controlled) on chemical anti-arrhythmic(s) must have cardiac consult to ensure the subject could safely proceed with protocol requirements
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
Be willing and able to provide written informed consent/assent for the trial; the subject may also provide consent for future biomedical research; however, the subject may participate in the main trial without participating in future biomedical research
Any concomitant disease or condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk
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:
If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least four weeks prior to the first dose of ARQ 751. a. Initiation of bisphosphonates during the study may be allowed provided the subject completes the first cycle of treatment without any dose limiting toxicity (DLT) and the Investigator rules out tumor progression.
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
Inclusion Criteria:\n\n Subject must have had a diagnosis of primary or secondary warm antibody AIHA.\n\n - Must have failed at least 1 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 < 30,000/?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 ? 130 mmHg, or diastolic blood pressure ? 80 mmHg.
The subject must be able to swallow ribociclib (LEE011)
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.
Any mental or physical condition, in the opinion of the Principal Investigator (PI) (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study
Subject has a positive serum Yo antibody (does not need to be repeated if performed in the past)
Subject has a chronic or acute hepatitis C infection; subject with an old infection that has cleared may be included
Subject has a chronic or acute hepatitis B infection; subject with an old infection that has cleared may be included
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 tolerated prior dose of modified T cell infusion without experiencing a dose limiting toxicity
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
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
Failure to obtain insurance/payment authorization for Zevalin, unless the subject agrees to cover the cost
History of venous or arterial thromboembolism, unless:\r\n* Line-related thrombosis without embolus occurring >= 1 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:
1) Subject has [follicular lymphoma that has progressed within 24 months of first diagnosis and treatment with combination chemoimmunotherapy] (e.g. R-bendamustine, R-CHOP) OR Progression of iNHL within 6 months of completion of second or later line therapy containing both an anti-CD20 antibody and alkylating agent OR Progression of iNHL at any point following autologous transplantation. 2) Subject has [measurable disease]. 3) Subject has no known presence or history of CNS involvement by lymphoma. 4) If subject is on conventional systemic therapy or systemic inhibitory/stimulatory immune checkpoint therapy, subject is able to stop conventional therapy 2 weeks or 5 half-lives, whichever is shorter, or immune checkpoint therapy 3 half-lives prior to planned leukapheresis. 5) Subject has ECOG performance status of 0-1 and adequate renal, hepatic, pulmonary, and cardiac function 6) Subject is not pregnant or breastfeeding (female subjects only) and is willing to use birth control from the time of consent through 6 months following CAR T cell infusion (both male and female subjects).B24
1) Transformed FL 2) Small lymphocytic lymphoma 3) Histological Grade 3b FL 4) Subject will have undergone autologous transplant within 6 weeks of planned leukapheresis or has undergone allogeneic transplant. 5) Subject has evidence of involvement of the heart by lymphoma or requirement for urgent therapy due to ongoing or impending oncologic emergency (e.g. mass effect, tumor lysis syndrome, etc.)
Inclusion Criteria:\n\n All subjects must meet the following criteria for admission into the study:\n\n 1. Signed informed consent has been obtained.\n\n 2. Subject is at least 21 years of age.\n\n 3. Diagnosis of mycosis fungoides (MF) or Sézary 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 8.4 for details).\n\n 4. Completion of the mSWAT assessment.\n\n 5. A history of pruritus that meets following criteria:\n\n At Screening Day -7:\n\n - present on a daily basis for greater than one month prior to Screening Day -7,\n\n - NRS for Pruritus score ?5 as rated by the subject at the Day -7 Visit. Note: If\n the score is <5 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 -7 Visit procedures after washout.\n\n At Baseline Period 1 Day 0:\n\n - NRS for Pruritus score of at least 5 recorded in the subject diary on at least 4\n of the 7 days preceding Baseline Period 1 Day 0.\n\n 6. Pruritic treatment area of 5-95% of the subject's total treatable body surface area.\n\n 7. Subject can be expected to reliably follow treatment instructions and visit schedule.\n\n 8. 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 ? 1 year). A negative urine pregnancy\n test must be confirmed at Baseline screening for all female subjects who are not\n post-menopausal > 1 year or surgically sterile.\n\n 9. 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 10. 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 11. Subject is able to speak, read, and write English and agrees to participate and comply\n with the study procedures.\n\n 12. Subject has a body mass index (BMI) between 18.5 and 30.5 kglm2 (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 1. Pregnant or lactating female.\n\n 2. History of clinically significant heart failure.\n\n 3. Myocardial infarction within the past six months.\n\n 4. A history of ventricular arrhythmia requiring treatment.\n\n 5. Any medical condition which would, in the Investigator's opinion, preclude the subject\n from successfully participating in the study.\n\n 6. A known allergy to naloxone hydrochloride or any excipient in the formulation.\n\n 7. Previous naloxone use for pruritus.\n\n 8. Positive urine drug screen at Day 0 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 9. Treatment with any of the following during the restricted time period prior to Day -7,\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) 7 days, Topical antihistamines to any\n skin surface [e.g. Zonalon® (doxepin)] 7 days, Other investigational drugs (excluding any\n therapies for the treatment of MF or SS) 30 days
Subject with recent gastric bleeding or symptomatic subjects with proven gastric ulcers that would exclude the subject from participation.
In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Malignancy other than disease under study with the exception of those from which the subject has been disease-free for more than 2 years and not expected to affect the safety of the subject or the endpoints of the trial.
Subject has HNSCC with carotid artery encasement
Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
The subject presents with:
Subject is willing to be randomized between intervention and control arms
Cases in which the subject has a solitary or horseshoe kidney
Cases in which the subject has more than two masses in the applicable kidney
For France only: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
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 2 years.
Inclusion Criteria:\n\n Subjects must satisfy the following criteria to be enrolled in the study:\n\n 1. Subject is ? 18 years of age the time of signing the informed consent form (ICF).\n\n 2. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted.\n\n 3. Subject is willing and able to adhere to the study visit schedule and other protocol\n requirements.\n\n 4. 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 ? 20% leukemic blasts in the bone marrow: -Have an Isocitrate\n dehydrogenase 1 (IDH1) or Isocitrate dehydrogenase 2 (IDH2) gene mutation (R132, R140,\n or R172)\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 5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or\n 2.\n\n 6. Subject has adequate organ function defined as:\n\n - Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase\n (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ? 3 x ULN, unless considered\n due to leukemic organ involvement.\n\n - Serum total bilirubin < 1.5 x ULN. Higher levels are acceptable if these can be\n attributed to ineffective erythropoiesis, 3 times the upper limit of normal for\n Gilbert's syndrome (eg, a gene mutation in UGT1A1), or leukemic organ\n involvement.\n\n - Serum creatinine < 2 x ULN or creatinine clearance > 30 mL/min based on the\n Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR):\n\n GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if\n African American)\n\n 7. Agree to serial bone marrow aspirate/biopsies.\n\n 8. 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 4 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 25 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 25 mIU/mL) within 72\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 72-hour\n timeframe).\n\n 9. 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 4 months following the last study treatment (6\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 4 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 1. Subject is suspected or proven to have acute promyelocytic leukemia based on\n morphology, immunophenotype, molecular assay, or karyotype.\n\n 2. Subject has AML secondary to chronic myelogenous leukemia (CML).\n\n 3. Subject has received a targeted agent against an Isocitrate dehydrogenase 1 (IDH1) or\n Isocitrate dehydrogenase 2 (IDH2) mutation.\n\n 4. 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 72 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 5. Subject has received more than 1 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 1st cycle of azacitidine (7 days) can be screened for the\n study. On study, Cycle 1 must be started at 28 days (+/- 3 days) after initiation of\n the pre-study azacitidine.\n\n 6. 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 7. 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 8. Subject has significant active cardiac disease within 6 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) < 40% by echocardiogram (ECHO) or multi-gated\n acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment.\n\n 9. 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 ? 1 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 (T1a or T1b using the tumor,\n node, metastasis clinical staging system)\n\n 10. 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 11. 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 12. Subject has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or\n diastolic BP > 100 mmHg)\n\n 13. 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 5 half-lives prior to the start of study treatment:\n phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and\n tizanidine (CYP1A2).\n\n 14. 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 5 half-lives prior to the start of study\n treatment.\n\n 15. 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 16. Subject has known or suspected hypersensitivity to any of the components of study\n therapy.\n\n 17. Subject is taking medications that are known to prolong the QT interval unless he/she\n can be transferred to other medications within ? 5 half-lives prior to the start of\n study treatment.\n\n 18. Subject has Heart rate-corrected QT (QTc) interval (ie, Fridericia's correction\n [QTcF]) ? 450 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 19. Female subject who is pregnant or lactating.\n\n 20. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n illness that would prevent the subject from participating in the study.\n\n 21. 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 22. Subject has any condition that confounds the ability to interpret data from the study.
Subject has an air leak ? 100 mL/min, as measured by a digital thoracic drainage system (DTDS)
Subject has air leak present on at least the 5th day following origination.
Subject has air leak only on forced exhalation or cough
Subject has sepsis
Subject has pneumonia
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
Subject meets institutional requirements for IL-2 therapy
Subject has any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications
At least 60 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 requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
For subjects in the UK only: Refusal of permission to allow the subject's General Practitioner to be notified of their participation in the study.
Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
Subject has had prior treatment with lenalidomide. 7. Subject is pregnant or lactating.
High-grade Ta papillary disease based on a biopsy within 8 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 8 weeks. This diagnosis must be confirmed by the independent central pathology reviewer prior to subject enrollment. A subject with persistent T1 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 ?1 prior treatment with a combination chemoimmunotherapy regimen.
Subject has a known dysfibrinogenemia, hypofibrinogenemia or a fibrinogenemia, without preoperative correction of fibrinogen levels.
Subject participating in studies involving approved drug or device will be enrolled only following a mutual consideration of the investigator together with the Sponsor.
Subject requires additional unrelated anastomosis during the surgery.
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 12 months of completing said therapy.
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 1. Subject is ?18 years of age at the time of signing the informed consent form (ICF).\n\n 2. 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 2016 criteria.\n\n 3. Subject has anemia defined as:\n\n 1. Cohorts 1 and 3A\n\n - Obtain ? 3 Hemoglobin (Hgb) levels of ? 9.5 g/dL recorded on ? 3 different\n days, including the day of dosing, in the 84-day period immediately up to\n the C1D1 date. There must be ? 14 days in between each Hgb measurement. No\n subjects with an interval ? 42 days between hemoglobin measurements will be\n enrolled.\n\n - There must not be any Red blood cell (RBC) transfusions within the 84-day\n period immediately up to the C1D1 date.\n\n 2. Cohorts 2 and 3B\n\n - Average RBC-transfusion frequency: 2 to 4 RBC units/28 days over at least\n the 84 days immediately up to the C1D1 date. There must be no interval > 42\n days without ? 1 RBC-transfusion.\n\n - Subjects must have a Hgb value of < 13 g/dL on C1D1 prior to luspatercept\n administration.\n\n - Only RBC transfusions given when the Hgb ? 9.5 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 4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ? 2.\n\n 5. Subject is not anticipated during the 6 months from the C1D1 date to receive a\n hematopoietic cell transplant.\n\n 6. A female of childbearing potential (FCBP) for this study is defined as a female who:\n 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or\n bilateral therapy does not rule out childbearing potential) for at least 24\n consecutive months (ie, has had menses at any time in the preceding 24 consecutive\n months). FCBP participating in the study must:\n\n 1. Have 2 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 2. 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, 28 days prior to\n starting investigational product, during the study therapy (including dose\n interruptions), and for 12 weeks (approximately 5 times the mean terminal\n halflife of luspatercept based on multiple-dose pharmacokinetics [PK] data) after\n discontinuation of study therapy.\n\n 7. 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 12 weeks (approximately 5 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 8. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted.\n\n 9. 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 1. Subject use of hydroxyurea or other drugs with potential effects on hematopoiesis or\n ongoing adverse events from previous treatment ? 112 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 ? 84 days immediately up to\n enrollment and is receiving a constant dose equivalent to ? 10 mg prednisone for the\n 28 days immediately up to enrollment.\n\n 2. Cohort 1 and 2 only: subjects treated with Janus kinase 2 gene (JAK2) inhibitors ? 112\n days immediately up to the enrollment date or if anticipated/substantial likelihood\n for subject to receive ruxolitinib within the first 168 days on the study.\n\n 3. Cohort 3 only: subjects not receiving a stable dose of ruxolitinib as part of their\n standard-of-care therapy for 112 days immediately up to the enrollment date.\n\n 4. Subject use of ESAs or androgenic steroids ? 112 days immediately up to the enrollment\n date.\n\n 5. Initiation of iron chelation therapy (ICT) or change with ICT dose within ? 112 days\n up to the enrollment date.\n\n 6. Subject with anemia from iron deficiency, B12 and folate deficiencies, hemolytic\n anemia, infection, or bleeding.\n\n 7. Pregnant or breastfeeding females.\n\n 8. Subject with blood myeloblasts ? 5%.\n\n 9. Subject with major surgery within 8 weeks up to the enrollment date. Subject must have\n completely recovered from any previous surgery immediately up to the enrollment date.\n\n 10. Subject with prior history of malignancies, other than disease under study, unless the\n subject has been free of the disease for ? 5 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 (T1a or T1b using the tumor,\n nodes, metastasis [TNM] clinical staging system)\n\n 11. Subject with prior therapy of luspatercept or sotatercept.\n\n 12. Subject participation in any other clinical protocol or investigational trial that\n involves administration of experimental therapy and/or therapeutic devices within 30\n days immediately up to the enrollment date.\n\n 13. Subject with prior hematopoietic cell transplant.\n\n 14. Subject with any of the following laboratory abnormalities:\n\n - Neutrophils < 1 x 109/L\n\n - White blood count (WBC) > 100 x 109/L\n\n - Platelets\n\n - Cohorts 1 and 2: < 25 x 109/L\n\n - Cohort 3A and 3B: < 50 x 109/L\n\n - All Cohorts: > 1000 x 109/L\n\n - Estimated glomerular filtration rate < 45 mL/min/1.73 m2 (via the 4-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) > 3.0 x upper\n limit of normal (ULN)\n\n - Direct bilirubin ? 2 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 15. Subject with stroke, deep venous thrombosis, pulmonary or arterial embolism within 6\n months immediately up to the enrollment date.\n\n 16. Subject with diastolic blood pressure ? 90 mmHg or systolic blood pressure ? 140 mmHg\n measured during the Screening Period despite appropriate treatment.\n\n 17. Subject with inadequately controlled heart disease and/or have a known left\n ventricular ejection fraction <35%.\n\n 18. 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 19. 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 20. Subject with human immunodeficiency virus (HIV), evidence of active infectious\n Hepatitis B (HepB), and/or evidence of active Hepatitis C (HepC).\n\n 21. 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 22. 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 23. Subject with any condition or concomitant medication that confounds the ability to\n interpret data from the study.\n\n 24. Subject on anticoagulant therapy not under appropriate control or subject not on a\n stable dose of anticoagulant therapy for ? 8 weeks up to the enrollment date.\n\n 25. Subject on anagrelide within 28 days immediately up to the enrollment date.\n\n 26. 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 ? 2g/dL or leading\n to transfusion of ? 2 units of packed red cells) in the last 6 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;
Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4 weeks prior to day 1.
In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Subject is on any systemic steroid therapy, within one week before the planned date for first dose of study treatment. Subject is on any other form of immunosuppressive medication
Subject must be deriving benefit from continued treatment without any persistent intolerable toxicity from continued treatment of ASP2215.
Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
The subject has had a hypoglycemic episode requiring medical intervention while on insulin (or other anti-diabetic) treatment within 12 months before Day 1.
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
Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
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.
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.
Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk
Subject is considered an adult according to local regulation at the time of obtaining informed consent.
Subject has any of the following comorbidities:
Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
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 a documented severe congenital or acquired immunodeficiency;
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 4 weeks prior to initiating study treatment\r\n* The subject has no new or progressive neurologic symptoms AND neurological symptom stability for the last 4 weeks prior to the study\r\n* The subject has been off of corticosteroids for at least 7 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 1. Male or female subject is between 18 and 65 years of age at the time of signing the\n Informed Consent Form (ICF).\n\n 2. Subject has definitive histologically or cytologically confirmed metastatic pancreatic\n adenocarcinoma.\n\n 3. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.\n\n 4. 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 1.1.\n\n 5. Subject has the following blood counts / Hemoglobin (Hgb) at screening:\n\n - Absolute neutrophil count (ANC) ? 1.5 × 10^9/L;\n\n - Platelet count ? 100,000/mm3 (100 × 10^9/L);\n\n - Hgb ? LLN or 10 g/dL.\n\n 6. Subject has the following blood chemistry levels at screening:\n\n - AST (SGOT), ALT (SGPT) ? 2.5 x upper limit of normal range (ULN); if hepatic\n metastases present ? 5.0 x ULN\n\n - Total bilirubin ? 1.5 X ULN\n\n - Creatinine clearance ? 60 mL/min (by Cockroft-Gault)\n\n - Albumin ? 3.5 grams/dL7.\n\n 7. Females of childbearing potential (FOCBP) [defined as a sexually mature woman who (1)\n have not undergone hysterectomy (the surgical removal of the uterus) or bilateral\n oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally\n postmenopausal for at least 24 consecutive months (ie, has had menses at any time\n during the preceding 24 consecutive months)] must:\n\n - Have a negative pregnancy test (?-human chorionic gonadotropin [? -hCG]) as\n verified by the study doctor within 72 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 6 months following last dose of study\n IP.\n\n 8. 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 6 months following last dose of study IP.\n\n 9. Subject has no clinically significant abnormalities in urinalysis results at baseline.\n\n 10. Subject is able to adhere to the study visit schedule and other protocol requirements.\n\n 11. 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 12. Subject must consent to provide protocol-mandated tumor and blood samples for\n molecular analysis.\n\n 13. 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 1. 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 2. Subject has known brain metastases unless previously treated and controlled for a\n minimum of 2 weeks prior to enrollment. Subject is not receiving corticosteroids with\n no evidence of cerebral edema.\n\n 3. Pre-existing peripheral neuropathy > Grade 1\n\n 4. Subject with unstable stent.\n\n 5. History of malignancy in the last 3 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 3 years.\n\n 6. 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 7. 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 8. 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 4 weeks prior to\n Day 1 of treatment in this study or surgical wound has not fully healed.\n\n 9. 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 10. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).\n\n 11. 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 12. 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 ? 3 (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 6 months\n\n - coronary stenting\n\n - myocardial infarction\n\n - coronary bypass surgery\n\n 13. Recent history of clinically significant hemoptysis.\n\n 14. Pregnant and nursing (lactating) women.\n\n 15. Any significant medical condition, laboratory abnormality, or psychiatric illness that\n would prevent the subject from participating in the study.\n\n 16. 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 17. Subject has any condition that confounds the ability to interpret data from the study.
Subject's lesions are not amenable to local therapies which may be beneficial, such as transarterial chemoembolization (TACE), radiofrequency ablation, radiotherapy, etc., and the subject is not a candidate for any curative treatments such as resection or liver transplant.
Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
Has known active Hepatitis B unless subject has been on antiviral agents for at least 2 months (baseline testing not required)
Subject had disease refractory to an AI
The subject has evidence of wound dehiscence
Subjects with signs or symptoms of other major diseases including, but not limited to: end organ failure, major chronic illnesses other than cancer, coagulation disorders, hemolytic conditions (eg, sickle cell disease ) or active infections that, in the opinion of the investigator, make it undesirable for the subject to participate in the study.
greater than or equal to 60 to 74 years will be eligible if the subjects has at least one of the following co-morbidities, which make the subject unfit for intensive chemotherapy:
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.
For subject eligibility and withdrawal, QT correction formula QTcB will be used.
Subject has active and uncontrolled autoimmune cytopenia
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:
Subject is currently being treated with anti-epileptics.
Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
Subject was diagnosed as acute promyelocytic leukemia (APL) or AML with good risk cytogenetics; t(8;21), inv(16) or t(16;16). (Subjects with pending cytogenetics that require treatment may enroll. Any subject that is found to have good risk cytogenetics after initiation of treatment will discontinue ASP2215 and be taken off trial).
Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Inclusion Criteria:\n\n Subjects must satisfy the following criteria to be enrolled in the study:\n\n 1. Subject is ? 18 years of age at the time of signing the informed consent form (ICF).\n\n 2. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted.\n\n 3. Subject is willing and able to adhere to the study visit schedule and other protocol\n requirements.\n\n 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.\n\n 5. Subjects must have a documented diagnosis of MM and measurable disease at enrollment.\n\n 6. Subjects must have the following laboratory values:\n\n - Absolute neutrophil count (ANC) ? 1.25 x 109/L without growth factor support for\n ? 7 days (? 14 days for pegfilgrastim).\n\n - Hemoglobin (Hgb) ? 8 g/dL.\n\n - Platelets (plt) ? 75 x 109/L without transfusion for ? 7 days (? 50 x 109/L for\n subjects with > 50% plasma cells in bone marrow).\n\n - Corrected serum calcium ? 13.5 mg/dL (? 3.4 mmol/L).\n\n - 24-hr creatinine clearance (CrCl) ? 45 mL/min.\n\n - AST/SGOT and ALT/SGPT ? 3.0 x upper limit of normal (ULN).\n\n - Serum bilirubin ? 1.5 x ULN.\n\n - Uric acid ? 7.5 mg/dL (446 ?mol/L).\n\n - PT/INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN, (for\n subjects not receiving therapeutic anticoagulation).\n\n 7. Females of childbearing potential (FCBP) must:\n\n 1. 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-92480. This applies even if\n the subject practices true abstinence* from heterosexual contact.\n\n 2. 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, 28 days\n prior to starting CC-92480, during the study therapy (including during dose\n interruptions), and for 28 days after discontinuation of study therapy.\n\n 8. Male subjects must:\n\n 1. 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 3 months following CC-92480 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 1. Subject has a significant medical condition, laboratory abnormality, or psychiatric\n illness that would prevent the subject from participating in the study.\n\n 2. 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 3. Subject has any condition that confounds the ability to interpret data from the study.\n\n 4. Subject has non- or oligosecretory multiple myeloma.\n\n 5. Subject has plasma cell leukemia or active leptomeningeal myelomatosis.\n\n 6. Subject has documented, systemic light chain amyloidosis or Polyneuropathy,\n Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS)\n Syndrome.\n\n 7. Subject has immunoglobulin class M (IgM) myeloma.\n\n 8. Subject has a history of allogeneic bone marrow transplantation.\n\n 9. Subject is undergoing dialysis.\n\n 10. Subjects with peripheral neuropathy ? Grade 2.\n\n 11. Subjects with gastrointestinal disease that may significantly alter the absorption of\n CC-92480.\n\n 12. Subject has impaired cardiac function or clinically significant cardiac disease,\n including any of the following:\n\n - LVEF < 45% 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 ?6 months prior to starting CC-92480.\n\n - Unstable or poorly controlled angina pectoris, including the Prinzmetal variant\n of angina pectoris.\n\n 13. Concurrent administration of strong CYP3A modulators.\n\n 14. Subject had prior systemic myeloma treatment (approved or investigational) ? 5\n half-lives or 4 weeks prior to starting CC-92480, whichever is shorter.\n\n 15. Subject had major surgery ? 2 weeks prior to starting CC-92480.\n\n 16. Subject is a pregnant or nursing female or intends to become pregnant during\n participation in the study.\n\n 17. Subject has known human immunodeficiency virus (HIV) infection.\n\n 18. Subject has known active chronic hepatitis B or C virus (HBV/HCV) infection.\n\n 19. Subject has a history of concurrent second cancer requiring ongoing systemic\n treatment.\n\n 20. Subjects has a history of prior malignancy other than MM, unless the subject has been\n free of disease for ?3 years except for the following noninvasive malignancies treated\n with curative intent:\n\n 21. Subject has known or suspected hypersensitivity to the excipients contained in the\n formulation of CC-92480 or dexamethasone.\n\n 22. Subject has undergone either of the following within 14 days of initiating CC-92480:\n\n - Plasmapheresis.\n\n - Radiation therapy other than local therapy for symptomatic relief of MM\n associated bone lesions.\n\n 23. Subject has received immunosuppressive medication within 14 days prior to the first\n dose of CC-92480.
Inclusion criteria :\n\n I 01. Males or females enrolled in Phase 1 or Phase 2 studies of SAR245408 or SAR245409 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 02. 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 3\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 SAR245408 due to possible drug-drug interaction.\n\n I 03. 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 12 months. However,\n women who have been amenorrheic for 12 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 01. The subject discontinued the parental study due to toxicity\n\n E 02. Ongoing Grade 3 or higher Adverse Event (AE)\n\n E 03. Ongoing Serious Adverse Event (SAE)\n\n E 04. 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 1 of the initiation period\n\n E 05. The subject has any of the following laboratory values ? Common Terminology of\n Adverse Events (CTCAE) Grade 3\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 06. The subject has a baseline corrected QT interval (QTc) >481 msec or if a subject has\n had a QTc interval increase of ? 60 msec from parental protocol baseline to an absolute\n value of > 470 msec\n\n E 07. The subject has a known allergy or hypersensitivity to components of the study\n treatment formulation(s)\n\n E 08. 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.
Subjects enrolled in France: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Subject must have either:
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Subject has a positive serum Yo antibody
Subject whose groins are not accessible
Subject has hematopoietic failure at baseline as defined by one of the following:
If the subject received at least 4 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
Inclusion Criteria:\n\n Subjects must satisfy the following criteria to be enrolled in the study:\n\n 1. Subject has an eligible disease:\n\n - Primary Acute myeloid leukemia (AML) induction failure: no Complete Remission\n (CR) after 2 or more induction attempts or\n\n - Relapsed AML: not in CR after 1 or more cycles of standard re-induction\n chemotherapy\n\n - For relapsed subjects > 60 years of age, the 1 cycle of standard\n re-induction chemotherapy is not required if either of the following\n criteria is met:\n\n - relapse within 6 months of last chemotherapy\n\n - blast count <30% within 10 days of starting this protocol therapy or\n\n - Secondary AML (MDS transformation or treatment related):\n\n or\n\n • AML relapsed > 2 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 2 weeks prior to Visit 1.\n\n 2. Subject is ? 18 and ? 70 years of age at the time of signing the informed consent form\n (ICF).\n\n 3. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted.\n\n 4. Subject is willing and able to adhere to the study schedule and other protocol\n requirements.\n\n 5. Karnofsky Performance Status > 50%.\n\n 6. Ability to be off prednisone and other immunosuppressive drugs for at least 3 days\n prior to the PNK-007 cell infusion.\n\n 7. 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 8. Either commit to true abstinence from heterosexual contact or agree to use, and be\n able to comply with, effective contraception without interruption, 28 days prior to\n starting PNK-007, during the study therapy (including dose interruptions), and for 28\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 28 days following PNK-007 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 1. 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 2. 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 3. A subject has any condition that confounds the ability to interpret data from the\n study.\n\n 4. Subject has a body weight exceeding 120kg.\n\n 5. Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or\n alkaline phosphatase ? 2.5 x the upper limit of normal (ULN) at screening.\n\n 6. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at screening\n calculated using the Modification of Diet in Renal Disease Study equation or history\n of an abnormal eGFR < 60 and a decline of > 15 mL/min/1.73 m2 below normal in the past\n year.\n\n 7. Subject has a bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease)\n at screening.\n\n 8. Subject has had prior treatment with biologic antineoplastic agents no less than 7\n days before PNK-007 infusion and at least 5 half lives. For agents that have known\n Adverse Events (AEs) occurring beyond 7 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 9. Subject has bi-phenotypic acute leukemia.\n\n 10. Subject has had a transplant < 60 days prior to Visit 1 (Screening/Baseline visit).\n\n 11. Subject has had treatment for graft-versus-host disease < 30 days prior to Visit 1\n (Screening/Baseline visit).\n\n 12. Subject is pregnant or breastfeeding.\n\n 13. 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 14. Subject has active autoimmune disease other than controlled connective tissue disorder\n or those who are not on active therapy.\n\n 15. Subject is HIV positive.\n\n 16. 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 5 years prior to PNK-007\n infusion.\n\n 17. 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 18. Untreated chronic infection or treatment of any infection with systemic antibiotics\n within 2 weeks prior to dosing with PNK-007.\n\n 19. Subject has any other organ dysfunction (CTCAE Version 4.03 Grade 3) that will\n interfere with the administration of the therapy according to this protocol.\n\n 20. Subject has a resting left ventricular ejection fraction (LVEF) of < 35% 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-122 or touch the capsules, unless gloves are worn.
Subject has received previous systemic therapy for Hepatocellular carcinoma including sorafenib, chemotherapy and investigational agents 2. Subject has received any local anticancer therapy ? 4 weeks prior to baseline tumor evaluation 3. Subject has undergone major surgery within the last 4 weeks or minor surgery within the last 2 weeks prior to signing the Informed Consent Form or who have not recovered from surgery 4. Subject has received an investigational drug or therapy for disease other than Hepatocellular carcinoma within the last 4 weeks or 5 half-lives, whichever is shorter, prior to signing the Informed Consent Form 5. Subject has completed any radiation treatment less than 2 weeks prior to signing the Informed Consent Form 6. Subject has received the last dose of ?-interferon, ribavirin, sofobuvir and/or other antiviral therapies for Hepatitis C Virus (HCV) less than 4 weeks prior to signing the Informed Consent Form 7. Subject has any clinically significant bleeding, including bleeding from esophageal/gastric varices within ? 3 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 ? 3 months prior to signing the informed consent form). See Inclusion Criterion 10 8. Subjects requiring therapeutic anticoagulation with either warfarin or low molecular weight heparin. Low dose low molecular weight heparin for catheter maintenance are permitted 9. Subject has tumor invasion of stomach or duodenum 10. Subject has histologic proof of fibrolamellar carcinoma 11. Subjects with known symptomatic brain metastasis 12. 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 4.03) Grade 2, despite medical management, or any other significant GI disorder that could affect the absorption of either study drug 13. Subject has history of concurrent second cancers requiring active, ongoing systemic treatment. 14. Subject has a known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory) 15. Subject has peripheral neuropathy of at least NCI CTCAE Grade 2 16. Subject has a history of persistent skin rash of at least NCI CTCAE Grade 2 17. Subject has impaired cardiac function or clinically significant cardiac disease including any of the following:
Subjects with baseline blood pressure 140/90 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 100 pg/mL 18. 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 19. Subject has undergone liver transplantation or other solid organ transplantation requiring immunosuppression 20. 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 21. Subjects with history of non-healing wounds or ulcers, or bone fractures less than 3 months of a prior fracture 22. Subject is being treated with concomitant strong CYP3A4 inducers such as St. John's Wort, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital. The use of concomitant strong CYP3A4 inducers may decrease sorafenib plasma concentrations and must be avoided.
Subject is a female who is pregnant or is breast feeding 24. Subject is unwilling or unable to comply with the protocol, in the opinion of the investigator 25. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study 26. Subject has any condition that confounds the ability to interpret data from the study
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
French subjects: The French subject has participated in any study using an investigational study treatment(s) during the previous 28 days.
Inclusion Criteria:\n\n Subjects must satisfy the following criteria to be enrolled in the study:\n\n 1. Subject received at least 3 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 60 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 1 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 1 regimen containing a immunomodulatory agent\n their disease must be refractory to the most recent immunomodulatory agent\n containing regimen.\n\n 2. 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 3. Subject has measurable disease defined as:\n\n 1. M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis\n (uPEP): sPEP ? 0.5 g/dL or uPEP ? 200 mg/24 hours) and/or\n\n 2. Light chain MM without measurable disease in the serum or the urine: serum\n immunoglobulin free light chain ?10 mg/dL and abnormal serum immunoglobulin kappa\n lambda free light chain ratio\n\n 4. Subject achieved a response (minimal response [MR] or better) to at least 1 prior\n treatment regimen.\n\n 5. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2\n or less.\n\n 6. Subject's toxicities resulting from previous therapy (including peripheral neuropathy)\n have resolved or stabilized to ? Grade 1.\n\n 7. Subject is at least 18 years of age the time of signing the informed consent form\n (ICF).\n\n 8. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted.\n\n 9. Subject is willing and able to adhere to the study visit schedule and other protocol\n requirements.\n\n 10. Females of childbearing potential (FCBP) must:\n\n a. Have 2 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 72 hours prior to starting study treatment\n (Cycle 1, Day 1), 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), 28 days prior to starting\n study treatment, during the study therapy (including dose interruptions), and for at\n least 90 days after discontinuation of study treatment.\n\n c. Agree to abstain from breastfeeding during study participation and for at least 90\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 90 days after the final dose of DURVA\n or DARA, whichever is later.\n\n 11. Male subjects must:\n\n 1. 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 90 days following study treatment discontinuation,\n even if he has undergone a successful vasectomy.\n\n 2. Refrain from sperm donation for at least 90 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 1. Subject has had prior exposure to anti-CTLA-4, anti-PD-1 (Programmed cell death-1),\n anti-PD-L1 (Programmed death-ligand 1) Monoclonal antibody (mAbs), or cancer vaccines\n\n 2. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks\n before the date of randomization.\n\n 3. History of organ or allogeneic stem cell transplantation\n\n 4. Subject received any of the following within the last 14 days of initiating study\n treatment:\n\n 1. Plasmapheresis\n\n 2. Major surgery (as defined by the investigator)\n\n 3. Radiation therapy other than local therapy for myeloma associated bone lesions\n\n 4. 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 5. Subject received prior treatment with a monoclonal antibody within 5 half-lives of\n initiating study treatment, other than DARA.\n\n 6. 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 7. Subject has any of the following laboratory abnormalities:\n\n 1. Absolute neutrophil count (ANC) < 1,000/µL\n\n 2. Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to\n reach this level)\n\n 3. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject\n to reach this level)\n\n 4. Creatinine clearance (CrCl) < 45 mL/min (calculated using the Cockcroft-Gault\n formula or directly calculated from the 24-hour urine collection method)\n\n 5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)\n\n 6. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 ×\n upper limit of normal (ULN)\n\n 7. Serum total bilirubin > 1.5 × upper limit of normal (ULN) or > 3.0 mg/dL for\n subjects with documented Gilbert's syndrome\n\n 8. Subject has clinical evidence of central nervous system (CNS) or pulmonary\n leukostasis, disseminated intravascular coagulation, or CNS MM\n\n 9. Subject has known chronic obstructive pulmonary disease (COPD) with a forced\n expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that forced\n expiratory testing (FEV1) is required for subjects suspected of having COPD and\n subjects must be excluded if FEV1 is < 50% of predicted normal.\n\n 10. Subject has known moderate or severe persistent asthma within the past 2 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 11. Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome\n (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes),\n or amyloidosis\n\n 12. Subject has nonsecretory MM\n\n 13. Subject has known allergy or hypersensitivity to study drug formulations\n\n 14. 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 3 years prior to the start of treatment. The following are exceptions to this\n criterion:\n\n 1. Subjects with vitiligo or alopecia.\n\n 2. Subjects with hypothyroidism (eg, following Hashimoto's disease) stable on\n hormone replacement.\n\n 3. Psoriasis not requiring systemic treatment.\n\n 15. Subject has history of primary immunodeficiency\n\n 16. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active\n hepatitis B or active hepatitis A or C.\n\n 17. Subject has received live, attenuated vaccine within 30 days prior to the first dose\n of DURVA (NOTE: Subjects, if enrolled, should not receive live vaccine during the\n study and through 30 days after the last dose of DURVA)\n\n 18. Subject is currently using or has used immunosuppressive medication within 14 days\n prior to the first study dose of study treatment. The following are exceptions to this\n criterion:\n\n 1. Intranasal, topical, inhaled, or local steroid injections (eg, intra-articular\n injection).\n\n 2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of\n prednisone or equivalent.\n\n 3. Steroids as premedication for hypersensitivity reactions (eg, infusion-related\n reactions, computed tomography [CT] scan premedication).\n\n 19. Subject has any one of the following:\n\n 1. Clinically significant abnormal Electrocardiogram (ECG) finding at screening\n\n 2. Congestive heart failure (New York Heart Association Class III or IV)\n\n 3. Myocardial infarction within 12 months prior to starting study treatment\n\n 4. Unstable or poorly controlled angina pectoris, including Prinzmetal variant\n angina pectoris\n\n 20. Subject has prior history of malignancies, other than MM, unless the subject has been\n free of the disease for ? 5 years with the exception of the following noninvasive\n malignancies:\n\n 1. Basal cell carcinoma of the skin\n\n 2. Squamous cell carcinoma of the skin\n\n 3. Carcinoma in situ of the cervix\n\n 4. Carcinoma in situ of the breast\n\n 5. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM\n [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is\n curative\n\n 21. 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 22. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n illness that would prevent the subject from participating in the study\n\n 23. 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 24. Subject has any condition that confounds the ability to interpret data from the study
Prior malignancy is acceptable if the subject is considered to be cured; in most cases this will mean a 5-year disease-free period; contact the principal investigator for any specific question regarding this requirement
Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocol
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days
Subject has known significant cardiovascular disease or cerebrovascular accident within 3 months of enrollment, or within the timeframe as stipulated in the additional criteria outlined in the protocol.
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: > 18 years\n\n - Subject has documented diagnosis of Barrett's esophagus, maximum endoscopic length of\n no more than C2M5 (i.e. no more than 2cm of circumferential extent and no more than\n 5cm of tongues) containing HGD/EC as follows:\n\n - HGD or EC documented on biopsy within previous 6 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 2 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 7 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 >C2M5\n\n - The subject is pregnant or planning a pregnancy during the study period (12 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 1. Subject is ? 60 years of age at the time of signing the ICF\n\n 2. 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 3. 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-2 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 60 days] after the hypomethylating\n therapy.)\n\n 4. Subject has the following disease status:\n\n 1. Refractory to or relapsed after second- or third-line of intensive therapy for\n AML (eg, the \7 + 3\ regimen):\n\n at least 5% 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 2. Refractory to or relapsed after second- or third-line low-intensity AML therapy\n (eg, LDAC, azacitidine or decitabine):\n\n at least 5% leukemic blasts in bone marrow after at least 2 treatment cycles\n\n 5. 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 6. Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2\n (Appendix D)\n\n 7. Subject has IDH2 gene mutations tested centrally (using the \investigational use\n only\PCR assay, Abbott RealTime IDH2) 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 IDH2 gene mutation by local\n evaluation, the subject may be eligible for randomization with approval by the Medical\n Monitor.)\n\n 8. 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) ? 3\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 ? 1.5 x ULN, unless considered due to Gilbert's syndrome\n (eg, a gene mutation in UGT1A1) or leukemic organ involvement, following review\n by the Medical Monitor; and\n\n - Creatinine clearance > 30 mL/min based on the Modification of Diet in Renal\n Disease (MDRD) glomerular filtration rate (GFR):\n\n GFR (mL/min/1.73 m2) = 175 × (serum creatinine)-1.154 × (Age)-0.203 × (0.742 if\n female) × (1.212 if African American)\n\n 9. 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 4 months following the last study treatment (6 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 25 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 25 mIU/mL) within 72\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 72-hour\n timeframe).\n\n 10. 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 4 months following the last study treatment (6 months following the last\n dose of cytarabine; 6 months following the last dose of azacitidine in Canada)\n\n 11. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted\n\n 12. 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 1. Subject is suspected or proven to have acute promyelocytic leukemia based on\n morphology, immunophenotype, molecular assay, or karyotype\n\n 2. Subject has AML secondary to chronic myelogenous leukemia\n\n 3. Subject has received a targeted agent against an IDH2 mutation\n\n 4. Subject has received systemic anticancer therapy or radiotherapy < 14 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 72 hours prior to and after administration of azacitidine).\n\n 5. Subject has received non-cytotoxic or investigational agents < 14 days or 5\n half-lives, whichever is longer, prior to the start of study treatment\n\n 6. Subject has undergone HSCT within 60 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 7. Subject has persistent, clinically significant non-hematologic toxicities from prior\n therapies\n\n 8. 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 9. 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 10. 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 11. Subject has significant active cardiac disease within 6 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) < 40% by echocardiogram (ECHO) or\n multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of\n study treatment\n\n 12. Subject has prior history of malignancy, other than MDS, MPN or AML, unless the\n subject has been free of the disease for ? 1 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 (T1a or T1b using the tumor,\n node, metastasis clinical staging system)\n\n 13. 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 14. 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 15. Subjects has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or\n diastolic BP > 100 mmHg)\n\n 16. Subject is a pregnant or lactating female\n\n 17. Subject has known or suspected to have hypersensitivity to any of the components of\n study treatment\n\n 18. Subject is taking those medications (listed in Section 8.2) that are known to prolong\n QT interval unless the subject can be transferred to other medications at least 5\n half-lives prior to the start of study treatment\n\n 19. Subject has QTc interval (ie, Fridericia's correction [QTcF]) ? 450 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 20. 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 5 half-lives prior to the start of study treatment:\n paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S-mephenytoin (CYP2C19),\n thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2)\n\n 21. 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 5 half-lives prior to the start of study\n treatment\n\n 22. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n illness that would prevent the subject from participating in the study\n\n 23. 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 24. 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 requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor, with the exception of drugs that are considered absolutely essential for the care of the subject.
Subject has concomitant active second malignancies unless remission was achieved at least 3 years prior to study entry and subject is no longer on therapy for the malignancy.
Subject has not received fosbretabulin treatment in the study OX4218s
Subject has received either:
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.
Subject required treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
Key Inclusion Criteria:\n\n Male or female age ? 18 years with histologically confirmed diagnosis of melanoma and\n unresected stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c 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 ? 1.5 x\n upper limit of normal, and Eastern Cooperative Oncology Group (ECOG) performance status of\n 0 or 1, 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 3 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 1 ( HSV-1) 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?
Does the subject have any gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine?
The subject has a history of delayed healing/open wounds or diabetic ulcers.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
French subjects: The French subject has participated in any study using an investigational study treatment(s) during the previous 30 days.
total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable;
The subject has had another active malignancy within the past 3 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.
Subject has received rifampin within 4 days prior to first dose of ABT-263
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?0thal
Subject requires hospitalization
Subject had a painful crisis requiring hospitalization within the preceding 14 days or has experienced > 5 hospitalizations for VOC in the prior 6 months
Subject is hospitalized for a condition other than VOC
Subject has complications related to SCD
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Subject has completed a prior study utilizing ABT-806 or 111ln ABT-806 (ABT 806i) and the Investigator believes that continued treatment with ABT-806 is in the best interest of the subject.
The subject must have received tivozanib while enrolled in another protocol, must be tolerating study drug and must currently display clinical benefit. The length of time that a subject must be on the parent protocol before rolling over to this protocol will be dictated by the parent protocol.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
French and Korean subjects: the French or Korean subject has participated in any study using an investigational drug during the previous 30 days.
Progressive or massive organomegaly French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
subject elected not to undergo treatment with Gliadel wafer
The subject must have received intravenous fluid resuscitation
Subject has had chest compressions as part of CPR
Subject has uncontrolled hemorrhage
Subject has sustained extensive third-degree burns
Subject must be participating in an Astellas-sponsored ASP8273 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 ASP8273 treatment in the parent study.
Subject who requires the following medications will be excluded:
Inclusion Criteria: -\n\n Subject must have either • Relapsed or refractory Chronic Lymphocytic Leukemia/Small\n Lymphocytic Lymphoma (for Waves 2 or 3)\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 ? 1 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 1, 2, or 3, 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 3 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 ? 1 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 2.\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 > 6 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-2 or PI3K 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 14 days or 5 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 2 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 30 days prior to first dose of duvelisib or venetoclax.\n\n - Subject has received live or live attenuated vaccines within 6 weeks prior to first\n dose of duvelisib or venetoclax.\n\n - Subject has received the following within 7 days prior to the first dose of duvelisib\n or venetoclax:\n\n - Steroid therapy for anti-neoplastic treatment;\n\n - Strong and Moderate CYP3A inhibitors;\n\n - Strong and Moderate CYP3A inducers;\n\n - Chronic immunosuppressants, other than corticosteroids given at daily dose < 20\n mg prednisone equivalent for ITP or AIHA.
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 has participated in another clinical study for systemic therapy within 6 weeks of baseline.
EXCLUSION - STUDY 1: Under the circumstance that a subject develops CIPN during study 1, the subject will be withdrawn from the study but may be asked to participate in study 2
The subject is willing to consent to randomization of lavage vs. standard lavage
The subject does not have a surgical indication for pancreatectomy
SUBJECT: A child has plans to start a new treatment for attention/memory problems in the next 3 months.
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 has evidence, in the opinion of the PI, of either ongoing systemic or pleural infection
Subject is pregnant, planning to become pregnant, or is lactating. 4. Subject has a history of empyema. 5. Subject has a history of chylothorax. 6. Subject has an uncorrected coagulopathy. 7. Subject has a hypersensitivity to new or existing pleural catheter or it's components.
Subject has evidence, in the opinion of the Investigator, of either on-going systemic or pleural infection.
Subject has had a lobectomy or pneumonectomy on the side of the effusion. 10. 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 ?2 cm toward the side of the effusion. 15. Subject is receiving concurrent intrapleural chemotherapy or radiation therapy to the ipsilateral chest.
Subject is anticipated to have therapy with TKI continued for >= 3 months
Subject reported symptoms of vaginal infection with significant vaginal discharge or odor
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 2 years.
Subject has MF with evidence of persistent disease despite ruxolitinib monotherapy treatment, consisting of:
Subject is planned to undergo either of the following:
Subject has one of the following underlying diseases:
Subject has middle ear effusion upon clinical examination.
Subject is receiving sodium-thiosulfate or amifostine therapy with chemotherapy.
Subject is currently participating on a separate otoprotection clinical study.
Subject receiving radiotherapy alone as treatment for his/her haematologic malignancy.
Subject is in acute unstable condition
Subject does not fit into 129-Xe vest coil used for MRI
Subject cannot hold his/her breath for 15 seconds
Subject weighs more than 450 pounds or otherwise cannot be safely fit into the imaging system
Any condition that would preclude the subject from getting the required biopsy as stated in the protocol
Subject does not meet institutional MRI safety screening requirements
Ability to understand and carry out subject instructions
Male subject who is considering fathering a child or donating sperm during the study or for approximately 90 days after the last dose of study drugs
Inclusion Criteria:\n\n Subjects must satisfy the following criteria to be enrolled in the study:\n\n 1. Subject has eligible disease status:\n\n 1. Newly diagnosed and are undergoing induction therapy prior to undergoing first\n Autologous stem cell transplant (ASCT) or\n\n 2. Myeloma patients with prior relapse undergoing first ASCT. or\n\n 3. 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 2. Subject is > 18 and ? 70 years of age at the time of signing the informed consent form\n (ICF).\n\n 3. Subject must understand and voluntarily sign an ICF prior to any study-related\n assessments/procedures being conducted.\n\n 4. Subject is willing and able to adhere to the study schedule and other protocol\n requirements.\n\n 5. Performance status of Karnofsky performance status ? 70% or Eastern Cooperative\n Oncology Group (ECOG) < 2\n\n 6. Ability to be off immunosuppressive drugs for at least 3 days prior to the PNK-007\n cell infusion. Steroids at the equivalent of no more than 5 mg prednisone per day are\n permissible.\n\n 7. Be a candidate for ASCT based on institutional practices.\n\n 8. Subjects must have autologous peripheral blood stem cell graft available in storage\n for additional transplant in the event of engraftment failure.\n\n 9. Female of childbearing potential (FCBP) must:\n\n 1. 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 2. 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 28 days after\n discontinuation of PNK-007.\n\n A female of childbearing potential (FCBP) is a female who:\n\n 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or\n bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea\n following cancer therapy does not rule out childbearing potential) for at least\n 24 consecutive months (ie, has had menses at any time in the preceding 24\n consecutive months).\n\n 10. Male subjects must:\n\n 1. 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 28 days following PNK-007\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 1. Subject has plasma cell leukemia.\n\n 2. Subject has non-secretory myeloma.\n\n 3. Subject has previously undergone allogeneic stem cell transplant.\n\n 4. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n illness that would prevent the subject from participating in the study.\n\n 5. 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 6. Subject has any condition that confounds the ability to interpret data from the study.\n\n 7. Subject has a body weight exceeding 120 kg.\n\n 8. Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or\n alkaline phosphatase ? 2.5 x the upper limit of normal (ULN) at screening.\n\n 9. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at screening\n calculated using the Modification of Diet in Renal Disease Study equation.\n\n 10. Subject has a bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease)\n at screening.\n\n 11. Subject has had prior treatment with biologic antineoplastic agents no less than 7\n days before PNK-007 infusion and at least 5 half-lives. For agents that have known AEs\n occurring beyond 7 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 12. Subject is pregnant or breastfeeding.\n\n 13. 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 14. Subject has active autoimmune disease other than controlled connective tissue disorder\n or those who are not on active therapy.\n\n 15. Subject has human immunodeficiency virus (HIV) are excluded due to increased risk of\n lethal infections when treated with myeloablative chemotherapy.\n\n 16. Subject has history of malignancy, other than multiple myeloma (MM), unless the\n subject has been free of disease for > 3 years from the date of signing the ICF.\n Exceptions include the following:\n\n 1. Basal cell carcinoma of the skin\n\n 2. Squamous cell carcinoma of the skin\n\n 3. Carcinoma in situ of the cervix\n\n 4. Carcinoma in situ of the breast\n\n 5. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)\n\n 17. 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 18. Untreated chronic infection or treatment of any infection with systemic antibiotics\n within 2 weeks prior to melphalan.\n\n 19. Subject has any other organ dysfunction that will interfere with the administration of\n the therapy according to this protocol.\n\n 20. Subject has a resting left ventricular ejection fraction (LVEF) of < 35% obtained by\n echocardiography or multigated acquisition scan (MUGA).\n\n 21. Subject was treated with an investigational product no less than 28 days before\n PNK-007 infusion. Subject must no longer be a participant in the previous\n interventional study at the time of the PNK-007 infusion.
Subject is < 2 months from the start of the last cycle of consolidation and should have completed the recommended number of consolidations per local practice.
Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
Subject's schedule permits compliance with all study procedures
EXCLUSION CRITERIA - FOR NORMAL HEALTHY FEMALE COHORT: Any condition, according to investigator's best judgement, that prevents the subject to participate in the trial
Subject must have histologic or cytologic confirmation of advanced melanoma
Subject enrolls into LCCC9819
FOCUS GROUP SUBJECT SELECTION
RANDOMIZED-CONTROLLED TRIAL SUBJECT SELECTION
Inclusion Criteria:\n\n Subjects who meet all of the following criteria may be enrolled in this Study:\n\n 1. Subject is male or female, age 18 or older.\n\n 2. Subject has undergone CT scan of the lung(s) that indicates one or more nodules or\n lesions suspicious for lung cancer.\n\n 3. Subject's pulmonary nodule or lesion is greater than 4mm. Size is determined by the\n largest nodule or lesion dimension identified from CT imaging.\n\n 4. 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 5. Subject must be able to receive a ProLung Test\n\n - within 60 days of abnormal CT (Inclusion Criterion 2 & 3)\n\n - within 60 days prior to the tissue biopsy or surgical resection (Inclusion\n Criterion 4).\n\n 6. Subject is capable of understanding and agreeing to fulfill the requirements of this\n Protocol.\n\n 7. 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 1. Subject has an implanted electronic device in the chest.\n\n 2. Subject receiving therapy for suspected chest infection such as fungal infection or\n tuberculosis.\n\n 3. 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 2 or more suspicious pulmonary nodules.\n\n 4. Subject has received an invasive medical or surgical procedure within the thoracic\n cavity within 30 days prior to the ProLung Test or within the previous 14 days for a\n bronchoscopic procedure.\n\n 5. Subject presents with an anomalous physical or anatomical condition that precludes\n ProLung Test measurement.\n\n 6. Subject will have undergone unusually strenuous exercise within 24 hours.\n\n 7. 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 1. Subject is male or female, age 18 or older.\n\n 2. Subject has undergone CT scan of the lung(s) that indicates one or more nodules or\n lesions suspicious for lung cancer.\n\n 3. Subject's pulmonary nodule or lesion is greater than 4mm. Size is determined by the\n largest nodule or lesion dimension identified from CT imaging.\n\n 4. 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 5. Subject must be able to receive a ProLung Test\n\n - within 60 days of abnormal CT (Inclusion Criterion 2 & 3)\n\n - within 60 days prior to the tissue biopsy or surgical resection (Inclusion\n Criterion 4).\n\n 6. Subject is capable of understanding and agreeing to fulfill the requirements of this\n Protocol.\n\n 7. 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 1. Subject has an implanted electronic device in the chest.\n\n 2. Subject receiving therapy for suspected chest infection such as fungal infection or\n tuberculosis.\n\n 3. 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 2 or more suspicious pulmonary nodules.\n\n 4. Subject has received an invasive medical or surgical procedure within the thoracic\n cavity within 30 days prior to the ProLung Test or within the previous 14 days for a\n bronchoscopic procedure.\n\n 5. Subject presents with an anomalous physical or anatomical condition that precludes\n ProLung Test measurement.\n\n 6. Subject will have undergone unusually strenuous exercise within 24 hours.\n\n 7. 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 2 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
Subject at risk of airway compromise in the event of postinjection tumor swelling/inflammation based on investigator judgment.
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.
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
Patient has any other medical, psychiatric, or social condition, including substance abuse, that in the opinion of the investigator would preclude compliance with the requirements of this study
Patients with any other medical condition or laboratory value that would, at the discretion of the investigator, preclude the patient from participation in this clinical study
Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
Any other condition which, in the opinion of the investigator, would preclude participation in this trial
Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel).
Any electrocardiogram (ECG) abnormality, which in the opinion of the Investigator would preclude safe participation in the study.
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
Any condition that in the opinion of the investigator, would preclude participation in this study
Any medical conditions that, in the opinion of the investigator, would preclude use of AGEN1884, including AGEN1884 hypersensitivity.
Any other serious medical condition which in the Investigator's opinion would preclude safe participation in the study.
Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
In the opinion of the principal investigator (PI), the participant has a condition that will preclude them from complying with study treatment
Any condition which, in the opinion of the investigator, would preclude participation in this trial
Any medical, psychological or social condition that in the opinion of the investigator, would preclude participation in this study.
Any other health condition that would preclude participation in the study in the judgment of the principal investigator
Other medical or psychiatric conditions that in the opinion of the investigator would preclude safe participation in the protocol
No other condition which, in the opinion of the Investigator, would preclude participation in this trial
Any condition which, in the opinion of the investigator, would preclude participation in this trial
Have a serious preexisting medical condition that, in the opinion of the investigator would preclude participation in the study (for example a GI disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome) or that would result in a life expectancy of less than 1 year
Any condition that in the opinion of the investigator, would preclude participation in this study
Any condition which, in the opinion of the investigator, would preclude participation in this trial
Any medical or other condition that, in the opinion of the investigator, would preclude the subject's participation in a clinical study
Any electrocardiogram (ECG) abnormality that in the opinion of the principal investigator would preclude safe participation in the study
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by P.I.)
Patients with a medical condition or social situation that at the discretion of the Principal Investigator (PI) would preclude them from completion of the trial
No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
Patients with psychosocial circumstances or illnesses that preclude protocol participation (to be determined by PI)
Co-morbid illnesses that preclude protocol participation (to be determined by PI)
Any condition which, in the opinion of the investigator, would preclude participation in this trial
RENAL & BLADDER: Any condition that in the opinion of the investigator, would preclude participation in this study
Other medical or psychiatric conditions that in the opinion of the investigator would preclude safe participation in the protocol
Any condition that in the opinion of the investigator, would preclude participation in this study
Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
Subject with any other condition which in the opinion of the investigator would preclude participation in the study.
have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study
Serious illness other than cancer that would preclude safe participation in the study.
Medical or psychiatric illness or social situations that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
Any condition that would preclude the ability to deliver appropriate IP therapy
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
Has an Underlying medical condition that would preclude study participation.
history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromise the patient's ability to give informed consent.
Have any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
Any medical or other condition that in the opinion of the investigator would preclude the subject's participation in a clinical study
Any condition that would preclude informed consent, consistent follow-up and compliance for the study participation
Any condition which, in the opinion of the investigator, would preclude participation in this trial
Any medical or other condition that in the opinion of the investigator(s) would preclude the subject's participation in a clinical study or would preclude them from completing the study.
Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves.
Any condition which, in the opinion of the investigator, would preclude participation in this trial
Subjects with a clinically significant or unstable medical condition that would preclude safe and complete study participation
No other significant medical or psychiatric problems that would preclude study participation or interfere with capacity to give informed consent.
Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel)
History of medical or psychiatric disease which, in the view of the principal investigator, would preclude safe treatment
Have serious preexisting medical conditions that, in the opinion of the investigator, that cannot be adequately controlled with appropriate therapy or would preclude participation in this study
Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial or the investigator’s belief that the subject is medically unfit to receive eribulin mesylate and atezolizumab or unsuitable for any other reason
The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
Any medical condition that would preclude adequate evaluation of the safety and toxicity of the study combination
Any other condition which, in the opinion of the Investigator, would preclude participation in this trial
Any medical condition that would preclude adequate evaluation of the safety and toxicity of the study combination
Any other condition which, in the opinion of the investigator, would preclude participation in this trial
Patient has any other medical, psychiatric, or social condition, including substance abuse that in the opinion of the investigator would preclude participation in the study.
Any condition, which in the opinion of the investigator, would preclude participation in this trial
Illness or any other circumstances (as defined by the investigator), which would preclude safe performance of study procedures or compromise the ability of the patient to consent to study
Any condition which, in the opinion of the investigator, would preclude participation in this trial
Any medical or other condition which, in the opinion of the PI or designee, will preclude participation in a clinical trial.
Have serious preexisting medical conditions that would preclude participation in the study
Any condition that in the opinion of the investigator, would preclude participation in this study
No known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder study adherence
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking intervention
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking intervention
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
Any condition that in the opinion of the investigator would preclude participation in this study
Psychiatric condition that would preclude or take precedence over study participation (e.g., active psychosis, suicidal ideation)
One or more significant medical conditions or other issues that in the physician’s judgment preclude participation in the walking intervention
Significant psychiatric disturbance sufficient, in the investigator's judgment, to preclude participation in the intervention (e.g., acute psychiatric symptoms which requires individual treatment)
In the opinion of the principal investigator (PI), the participant has a condition that will preclude them from complying with study treatment
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking or strength training intervention
One or more significant medical conditions that in the physician’s judgment preclude participation in the walking intervention
One or more significant medical conditions that in the treatment team’s judgment preclude participation in the walking intervention
Any condition that, in the opinion of the investigator, would preclude safe and adequate test performance
Significant co-morbidities (e.g., diabetes, cardiac disease, or other condition that in the opinion of the primary physician or investigators would limit participation in the intervention groups) that would preclude study participation
Other medical condition or laboratory value that would, at the discretion of the investigator, preclude the patient from participation in this clinical study
Uncontrolled illness or comorbidity that in the judgment of the principal investigator (PI) would preclude participation in the study
Any condition which, in the opinion of the investigator, would preclude participation in this trial
Patients with any other medical condition or laboratory value that would, at the discretion of the investigator, preclude the patient from participation in this clinical study.
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
Presence of concomitant intercurrent illness, or any condition which in the opinion of the Investigator, would compromise safe participation in the study, e.g. active severe infection, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia.
Any other active malignancy other than melanoma that, in the opinion of the investigator, would interfere with study participation (for treatment phase)
Has a medical condition that requires immunosuppression
Any other condition that may interfere with compliance of the study protocol
High likelihood of protocol non-compliance (in opinion of investigator)
Medical condition such as uncontrolled infection or cardiac disease that, in the opinion of the physician, would make this protocol unreasonably hazardous for the patient (see Section 4.4-4.10).
Any serious medical condition that interferes with adherence to study procedures.
Patient must not have a co-morbid condition(s) that, in the opinion of the investigator, prevent safe treatment
Any condition, in the opinion of the investigator, that compromises compliance with study requirements
In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer.
History of any major disease that might interfere with safe protocol participation, as determined by the investigator
Any serious medical condition that interferes with adherence to study procedures.
Any medical condition that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of study treatment
Serious cardiopulmonary medical condition
Any other medical or social condition that, in the opinion of the investigator, would not permit the patient to complete the study or sign informed consent
PROCUREMENT EXCLUSION CRITERIA: Patients with a chronic uncontrolled medical condition that, in the opinion of the principal investigator, precludes them from participation
Patients with a chronic uncontrolled medical condition that, in the opinion of the principal investigator, precludes them from participation
Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject’s ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results
Have other concurrent severe and/or uncontrolled medical condition that would, in the site Investigator's judgment contraindicate the patient's participation in the clinical study
Any significant psychiatric disease, medical or other condition, which in the opinion of the principal investigator could prevent adequate informed consent or compromise participation in the clinical trial
Any medical condition which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient; subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, laboratory tests, and according to the investigator’s judgment
Any other pathology or condition which the principal investigator may deem to negatively impact treatment safety
Patients who, in the opinion of the principal investigator, have significant medical or psychosocial problems that warrant exclusion including:\r\n* Other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy to less than 2 years\r\n* Any condition, medical, psychiatric or otherwise, that would preclude informed consent, consistent follow-up, or compliance with any aspect of the study
Patients whose comorbid medical condition, in the investigator’s opinion, would make participation in this trial and adherence to the protocol guidelines difficult should be excluded
Any other medical intervention or condition which could compromise adherence to study requirements or confound the interpretation of study results.
Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the investigator
Patients must NOT have any concurrent medical condition that, in the opinion of the PI or designee, would prevent the patient from undergoing protocol-based therapy; patients with a primary immunodeficiency/ bone marrow failure syndrome are excluded from this trial
Patients with rapidly progressing disease in the opinion of the principal investigator
Intercurrent illness that will interfere with the radiation therapy such as immunosuppression due to medication or medical condition
Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements.
Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the patient’s study physician to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with scheduled visits, treatment schedule, laboratory tests and other study requirements.
The recipient has another medical problem or neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery in which the opinion of the principal investigator would place the recipient at unacceptable risk
Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the long-term follow-up), or would interfere with the evaluation of the trial endpoints
Any other condition that in the investigator’s judgement would significantly increase the risks of participation.
Significant medical conditions (including widely disseminated metastatic disease) or laboratory results that, in the opinion of the investigator, indicate an increased vulnerability to study drugs and procedures.
Presence of a concomitant medical condition that (in the judgement of the investigator) interferes with the ability of the subject to participate in the study.
Any other medical condition (eg, alcohol abuse) or psychiatric condition that, in the opinion of the investigator, might interfere with the subject’s participation in the trial or interfere with the interpretation of trial results
In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer.
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study Cancer-Related Exclusion Criteria
Medical history that includes any condition, or requires the use of concomitant medications which, in the investigator's judgment, are associated with or create a risk of increased carotid sinus sensitivity, symptomatic bradycardia, or syncopal episodes.
Subjects must NOT have any concurrent medical condition that, in the opinion of the protocol PI or designee, would prevent the patient from undergoing protocol-based therapy; subjects with a primary immunodeficiency/bone marrow failure syndrome are excluded from this trial
Any other sound medical, psychiatric, and/or social reasons as determined by the investigator
Another significant medical, psychiatric, or surgical condition which is currently uncontrolled by treatment and which would likely affect the subject's ability to complete this protocol
Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the patient’s study physician to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with scheduled visits, treatment schedule, laboratory tests and other study requirements
Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject’s ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results.
Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe or ineligible for protocol procedures
Subjects must NOT have any concurrent medical condition that, in the opinion of the protocol PI or designee, would prevent the patient from undergoing protocol-based therapy; subjects with a primary immunodeficiency/bone marrow failure syndrome are excluded from this trial
Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment
Subjects with medical condition that could adversely impact the study participation or assessments.
Male subjects will be considered to be of non-reproductive potential if they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition)
Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study
Part of another study that may interfere with our outcome of interest, unstable mental condition
Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
History of severe eczema (as determined by the investigator) requiring medical treatment
Unstable or severe uncontrolled medical condition (e.g. unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the risk to the patient associated with his or her participation in the study
The presence of any medical condition that the Investigator deems incompatible with participation in the trial
Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject’s ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results
Any other pathology or condition that the principal investigator deems to negatively impact treatment safety
Patients with uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent.
Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, including any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the IP or procedures.
Patients with known diabetes whose glucose control or general health condition may be adversely affected by the use of metformin as per the study protocol as deemed by either the study investigator or endocrinologist are excluded
Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled
Concurrent severe and/or uncontrolled medical condition or psychiatric condition
Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with interpretation of the study results, or predispose the patient to safety risks.
Presence of underlying medical condition that in the opinion of the investigator or sponsor could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of DS-8273A and nivolumab in treated subjects
Has known serious neuropsychiatric condition
Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which cord blood [CB] transplantation is proposed), or psychiatric condition that would limit informed consent
Current evidence of any of the following:\r\n* Uncontrolled hypertension \r\n* Gastrointestinal disorder affecting absorption\r\n* Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated\r\n* Any condition that in the opinion of the investigator, would preclude participation in this study
Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results
Any medical condition which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient; subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, electrocardiogram (ECG), laboratory tests, or chest-X-ray and according to the investigator’s judgment
Patients with any other severe and/or uncontrolled concurrent disease affecting the cardiovascular system, liver, kidneys, hematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures/results or compromise compliance with the protocol.
Major medical conditions that might affect study participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) are not eligible; other significant comorbid condition which the investigator feels might compromise effective and safe participation in the study
Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the principal investigator
History of any other significant medical disease such as major gastric or small bowel surgery, recent drainage of significant volumes of ascites or pleural effusion (as per Investigator's judgement) or a psychiatric condition that might impair the subject's well-being or preclude full participation in the trial
Current evidence of any of the following:\r\n* Uncontrolled hypertension\r\n* Gastrointestinal disorder affecting absorption\r\n* Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis)\r\n* Any chronic medical condition requiring a dose of corticosteroid higher than 10 mg prednisone/prednisolone once daily\r\n* Any condition that, in the opinion of the site investigator, would preclude participation in this study\r\n* Moderate or severe hepatic impairment (Child Pugh class B or C)
Have any medical or social condition that, in the opinion of the Investigator, might place a subject at increased risk, affect compliance, or confound safety or other clinical trial data interpretation
Patients with other concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or places them at an unacceptable risk for participation in the study
Serious medical or psychiatric illness/condition likely in the judgment of the Investigator to interfere with compliance to protocol treatment/research
Active, uncontrolled infection, any other concurrent disease, or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
No active major medical or psychosocial problems that could be complicated by study participation
Life expectancy of ? 2 months. 6. Subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include: • Unstable cardiovascular conditions at Baseline including but not limited to:
Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence with study requirements or confound the interpretation of study results
Other investigational procedures while participating in this study that could affect the primary objective of the study as determined by the principal investigator (PI) are excluded
Major active medical or psychosocial problems that could be exacerbated by the study treatment
The recipient has a medical problem or neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the principal investigator would place the recipient at unacceptable risk
Any other medical condition for which the treating physicians deem might lead to unacceptable toxicity or morbidity for that treatment plan for the patient e.g., allergy to a component of therapy or a medical condition that might be aggravated by the therapy and increases potential risk of toxicity in the opinion of the treating physicians
History of psychiatric disorder or any other condition which may compromise compliance with transplant protocol or expose patient to unnecessary risk as determined by principal investigator or lead associate investigator
Patient does NOT have any concurrent medical condition that, in the opinion of the protocol PI or designee, would prevent the patient from undergoing protocol-based therapy; patients with a primary immunodeficiency/bone marrow failure syndrome are excluded from this trial
Any other pathology or condition where the principle investigator may deem to negatively impact treatment safety
Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen, or any other condition that puts the subject at an imminent risk of death.
Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
History of severe eczema (as determined by the Investigator) requiring medical treatment
Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the investigator
In the judgment of the investigator, participation in the protocol offers acceptable risk/benefit ratio when considering current NF2 disease status, medical condition, and the potential benefits of and risks of surgery or irradiation
No active major medical or psychosocial problems that could be complicated by study participation
Infection or any other severe systemic disease or medical or surgical condition deemed significant by the principal investigator
Any co morbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol
A serious underlying medical condition other than NSCLC such that life expectancy is less than 2 years.
Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject. Additional Exclusion Criteria for Cohort 1:
Any active and persistent dermatological condition
Any condition that prevents compliance with the protocol or adherence to therapy.
Patient with any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events Previous treatment
Have at least stable disease, as determined by the investigator.
Has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements.
Patients who, in the opinion of the principal investigator, have significant medical or psychosocial problems that warrant exclusion including:\r\n* Other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy to less than 2 years\r\n* Any condition- medical, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study
In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject’s ALL
History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.
In the investigator's judgment, any other condition that jeopardizes the patient's participation in the treatment phase
Any condition medical or psychosocial that in the opinion of the investigator would hinder compliance
Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results
Concurrent medical condition that precludes safe participation in this study
Evidence of any other serious medical condition (such as psychiatric illness, infectious diseases, physical or laboratory findings) that may interfere with the planned treatment, affect compliance or place the patient at high risk from treatment-related complications or potentially interfere with the completion of the treatment as per the protocol
History of and or medical condition (e.g. diverticular disease; aneurysm) that predisposes to risk of major hemorrhage
Any serious medical condition that interferes with adherence to study procedures.
History of intratumoral or peritumoral hemorrhage if deemed significant by the treating investigator; if there are questions, the treating investigator should contact the study overall principal investigator (P.I.), Eudocia Quant Lee, medical doctor (MD), at 617-632-2166 or eqlee@partners.org
Active infection or other medical condition that would make prednisone use contraindicated
Any other therapy or serious medical condition, as specified in the protocol, or abnormality in clinical laboratory tests that, in the investigator's judgement, precludes the participant's safe participation in and completion of the study
Any concurrent or past medical condition that, in the opinion of the Investigator, would exclude the subject from participation or any psychosocial conditions that would hinder study compliance or follow-up, at the discretion of the Investigator
No new or worsened existing acute medical condition that would require a dose hold or delay
Any other medical condition (eg, alcohol abuse) or psychiatric condition that, in the opinion of the Investigator, might interfere with the subject’s participation in the trial or interfere with the interpretation of trial results
Uncontrolled psychiatric condition
Any medical condition which in the opinion of the investigator puts the patient at risk of potentially serious complications while on this therapy
Patients may be excluded at the discretion of the PI/LAI if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk
Patients may be excluded at the discretion of the principal investigator (PI) or if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk
Subjects who, in the opinion of the Investigator, cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratory disorders).
c) History of other malignancy that in the Investigator's opinion would not affect the determination of study treatment effect
Subjects with other concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study, or places them at an unacceptable risk for participation in the study
Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study.
Subject has a concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases subject risk, in the opinion of the Investigator, such as but not limited to:
Patients with any medical condition, including alcohol or drug abuse or mental incapacity / hypersensitive to the study drug, which in judgment of the investigator will interfere with the patient's participation in the study or evaluation of study results
Serious infection, immunosuppression or concurrent medical condition (chronic or acute in nature) that may prevent safe participation or ability to meet follow-up requirements
No coexisting medical problems of sufficient severity to limit compliance with the study
Significant concurrent medical condition that would make prednisone/prednisolone use contraindicated or would interfere with the patient’s ability to participate in the trial
Another significant medical, psychiatric, or surgical condition which is currently uncontrolled by treatment and which would likely affect the subject's ability to complete this protocol
Patients with unstable or severe intercurrent medical conditions or laboratory abnormalities that would impart, in the judgment of the protocol principal investigator, excess risk associated with study participation or study agent administration
Have evidence of any other serious systemic disease, including active bacterial or fungal infection, or any medical condition that, in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
Subjects with pre-existing medical illnesses or medications which might interfere with the study as determined by principal investigator (PI)
Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator or the sponsor's medical monitor.
Any new condition or worsening of existing condition that could make the patient unsuitable for participation, or interfere with the patient participating in and/or completing the study
Subjects with pre-existing medical illnesses or medications which might interfere with the study as determined by principal investigator (PI)
Presence of underlying medical condition that in the opinion of the investigator or sponsor could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of panobinostat and ipilimumab in treated subjects
Requires myelofibrosis therapy, in the opinion of the investigator
Subject is diagnosed with a known medical condition associated with a hypercoagulable state.
Any other medical condition that in the opinion of the investigator may interfere with a subject participation in, or compliance with, the study
Physical abnormality or medical condition that limits swallowing multiple pills, or has a history of non-adherence to oral therapies.
No coexisting medical problems of sufficient severity to limit compliance with the study
Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, contraindicate patient participation in the clinical study (eg, chronic pancreatitis, etc.).
Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include, but are not limited to:
Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject’s ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results
Patient has any severe psychiatric disease that would interfere with participation in the trial as determined by the study investigator
Any other medical condition (eg, alcohol abuse) or psychiatric condition that, in the opinion of the investigator, might interfere with the subject’s participation in the trial or interfere with the interpretation of trial results
Any medical condition that precludes the surgery necessary to administer DNX-2401 into the tumor using the cannula
Having a history or presence of a significant psychiatric disorder or any other condition that, in the investigator’s judgment, would interfere with participation in the trial
Any medical condition which, in the opinion of the investigator, puts the patient at risk of potentially serious complications while on study treatment
Medical, social, or psychosocial factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures.
High likelihood or protocol non-compliance (in opinion of investigator)
Has any disease or condition that, per protocol or in the opinion of the investigator, might affect:
Any clinically significant medical or psychiatric condition that would interfere with protocol treatment
Any clinically significant medical or psychiatric condition that would interfere with protocol treatment
Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the long-term follow-up), or would interfere with the evaluation of the trial endpoints
the patient is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT
Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk
Any physical or mental condition or social situation that in the opinion of the Investigator may interfere with the patient's ability to comply with the trial procedures
Medical or other condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective
Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk
Concurrent and or uncontrolled psychiatric or medical condition which may interfere with the study completion
General medical condition: fit for the proposed surgery and/or radiation treatment as determined by the treating investigator
Any medical condition which would, in the investigator's opinion, compromise the patient's ability to mount an immune response, renders the patient a poor candidate for this trial or could confound the results of the study
No other serious medical condition that would interfere with follow-up
Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation; (excluding primary disease for which cord blood [CB] transplantation is proposed), or psychiatric condition that would limit informed consent
Has, in the Investigator's opinion, any medical condition that makes the subject a poor candidate for the investigational procedure, or interferes with the interpretation of study results.
Is actively participating in another investigational clinical study which, in the Investigator's or Sponsor's opinion, would interfere in this study.
Subject has a concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases subject risk, in the opinion of the Investigator, such as but not limited to:
Has an intercurrent (non-malignant) chronic medical or psychiatric illness or condition(s) not optimally controlled and carrying a moderate to high risk of interfering with protocol therapy administration or compliance with required procedures, in the judgment of the investigator
The presence of any medical condition that the Investigator deems incompatible with participation in the trial
DONOR: The presence of any medical condition that the investigator deems incompatible with participation in the trial
Concurrent clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram or laboratory finding that, in the opinion of the investigator, could adversely affect the safety of the subject or impair the assessment of the study results.
Any preexisting medical condition of sufficient severity to prevent full compliance with the study.
Any preexisting medical condition of sufficient severity to prevent full compliance with the study.
Any concurrent disease and/or medical condition that, in the opinion of the Investigator, would prevent the subject's participation.
Significant, concurrent, uncontrolled medical condition which, in the opinion of the investigator, may interfere with patient participation in the study.
Uncontrolled diabetes or other medical condition that may interfere with assessment of toxicity.
Subject has an existing medical condition that is likely to require repetitive MRI evaluation in the future (i.e. epilepsy, stroke, multiple sclerosis, acoustic neuroma, tumor)
Subject has an existing medical condition that is likely to require the use of diathermy in the future
Any other medical condition that, in the opinion of the principal investigator (PI), may interfere with a subject's participation in or compliance with the study
Any other medical condition that, in the opinion of the PI, may interfere with a subject's participation in or compliance with the study
Key Inclusion Criteria:\n\n - Received an autologous or allogeneic HCT using any conditioning regimen\n\n - Evidence of new abnormalities on chest X-ray obtained < 48 hours prior to screening,\n determined to be consistent with LRTI by the local radiologist, relative to the most\n recent previous chest X-ray. If chest X-ray is not available, a chest X-ray must be\n obtained for screening.\n\n - Documented RSV in both the upper (eg, nasal swab, nasopharyngeal swab, nasal wash) and\n lower (eg, induced sputum, bronchoalveolar lavage, lung biopsy, but not spontaneous\n sputum) respiratory tract as determined by local testing (eg, polymerase chain\n reaction, direct fluorescence antibody, respiratory viral panel assay, or culture).\n All samples must have been collected ? 6 days prior to Day 1, or as determined at\n screening as per protocol.\n\n - An informed consent document signed and dated by the participant or a legal guardian\n of the participant and investigator or his/her designee.\n\n - A negative urine or serum pregnancy test is required for female participants (unless\n surgically sterile or greater than two years post-menopausal)\n\n - Male and female participants of childbearing potential must agree to contraceptive\n requirements as described in the study protocol\n\n - Willingness to complete necessary study procedures and have available a working\n telephone or email\n\n Key Exclusion Criteria:\n\n Related to concomitant or previous medication use:\n\n - Use of non-marketed (according to region) investigational agents within 30 days, OR\n use of any monoclonal anti-RSV antibodies within 4 months or 5 half-lives of\n screening, whichever is longer, OR use of any investigational RSV vaccines after HCT\n\n - Use of a moderate or strong cytochrome P450 enzyme inducer including but not limited\n to rifampin, St. John's Wort, carbamazepine, phenytoin, efavirenz, bosentan,\n etravirine, modafinil, and nafcillin, within 2 weeks prior to the first dose of study\n drug\n\n Related to medical history:\n\n - Pregnant, breastfeeding, or lactating females\n\n - Unable to tolerate nasal sampling required for this study, as determined by the\n investigator\n\n - Known history of HIV/AIDS with a CD4 count <200 cells/?L within the last month\n\n - History of drug and/or alcohol abuse that, in the opinion of the investigator, may\n prevent adherence to study activities\n\n Related to medical conditions:\n\n - Requiring invasive mechanical ventilation at the time of randomization\n\n - Documented to be positive for other respiratory viruses (limited to influenza,\n parainfluenza, human rhinovirus, adenovirus, human metapneumovirus, or coronavirus),\n from the lower respiratory tract sample as determined by local testing\n\n - Clinically significant bacteremia or fungemia within 7 days prior to screening that\n has not been adequately treated, as determined by the investigator\n\n - Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to\n screening that has not been adequately treated, as determined by the investigator\n\n - Excessive nausea/vomiting at screening, as determined by the investigator, or an\n inability to swallow pills that precludes oral administration of the investigational\n medical product (for individuals without an NG tube in place)\n\n - Any condition which, in the opinion of the investigator, would prevent full\n participation in this trial or would interfere with the evaluation of the trial\n endpoints\n\n Related to laboratory results:\n\n - Creatinine clearance < 30 mL/min (calculated using the Cockcroft-Gault method)\n\n - Clinically significant aspartate aminotransferase/alanine aminotransferase, as\n determined by the investigator\n\n - Clinically significant total bilirubin, as determined by the investigator\n\n Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria:\n\n - Received an autologous or allogeneic HCT using any conditioning regimen\n\n - Documented to be RSV-positive as determined by local testing (eg, polymerase chain\n reaction, direct fluorescence antibody, respiratory viral panel assay, or culture)\n using an upper respiratory tract sample collected ? 6 days prior to Day 1\n\n - New onset of at least 1 of the following respiratory symptoms for ? 7 days prior to\n Day 1: nasal congestion, runny nose, cough, or sore throat, or worsening of one of\n these chronic (associated with a previously existing diagnosis, eg, chronic\n rhinorrhea, seasonal allergies, chronic lung disease) respiratory symptoms ? 7 days\n prior to Day 1\n\n - No evidence of new abnormalities consistent with LRTI on a chest X-ray relative to the\n most recent chest X-ray, as determined by the local radiologist. If a chest X-ray is\n not available or was not obtained during standard care < 48 hours prior to screening,\n a chest X-ray must be obtained for screening\n\n - O2 saturation ? 92% on room air\n\n - An informed consent document signed and dated by the participant or a legal guardian\n of the participant and the investigator or his/her designee\n\n - A negative urine or serum pregnancy test is required for female participants (unless\n surgically sterile or greater than two years post-menopausal)\n\n - Male and female participants of childbearing potential must agree to contraceptive\n requirements as described in the study protocol\n\n - Willingness to complete necessary study procedures and have available a working\n telephone or email\n\n Exclusion Criteria:\n\n Related to concomitant or previous medication use:\n\n - Use of non-marketed (according to region) investigational agents within 30 days, OR\n use of any monoclonal anti-RSV antibodies within 4 months or 5 half-lives of\n screening, whichever is longer, OR use of any investigational RSV vaccines after HCT\n\n Related to medical history:\n\n - Pregnant, breastfeeding, or lactating females\n\n - Unable to tolerate nasal sampling required for this study, as determined by the\n investigator\n\n - Known history of HIV/AIDS with a CD4 count <200 cells/?L within the last month\n\n - History of drug and/or alcohol abuse that, in the opinion of the investigator, may\n prevent adherence to study activities\n\n Related to medical condition at screening:\n\n - Documented to be positive for other respiratory viruses (limited to influenza,\n parainfluenza, human rhinovirus, adenovirus, or human metapneumovirus, or coronavirus)\n within 7 days prior to the screening visit, as determined by local testing (additional\n testing is not required)\n\n - Clinically significant bacteremia or fungemia within 7 days prior to screening that\n has not been adequately treated, as determined by the investigator\n\n - Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to\n screening that has not been adequately treated, as determined by the investigator\n\n - Excessive nausea/vomiting at screening, as determined by the investigator, or an\n inability to swallow pills that precludes oral administration of the investigational\n medical product (for participants without an nasogastric tube in place)\n\n - Any condition which, in the opinion of the investigator, would prevent full\n participation in this trial or would interfere with the evaluation of the trial\n endpoints\n\n Related to laboratory results:\n\n - Creatinine clearance < 30 mL/min (calculated using the Cockcroft-Gault method)\n\n - Clinically significant aspertate aminotransferase/alanine aminotransferase, as\n determined by the investigator\n\n - Clinically significant total bilirubin, as determined by the investigator
A medical condition that precludes adequate study treatment or increases patient risk
Requires myelofibrosis therapy, in the opinion of the investigator
Patient has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the subject including but not limited to uncontrolled infection, heart failure, pulmonary hypertension, etc.
Concomitant intercurrent illness, or any condition which in the opinion of the Investigator, would compromise safe participation in the study, e.g. active severe infection, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia
Subjects who, in the Investigator's opinion, have any medical condition that makes the subject a poor candidate for the investigational procedure, or interferes with the interpretation of study results.
Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that would, in the investigator's opinion, contraindicate participation in this study
Patients with uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent
Concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent)
Ongoing or recent history of any other uncontrolled and/or clinically significant systemic disease or condition which, in the Investigator's medical opinion, should exclude participation in the study
In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the individual's NHL
Any other clinically significant medical condition, psychiatric illness, and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol or which, in the views of investigator, preclude combination chemotherapy.
Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,
Patients with a co-morbid condition(s) that, in the opinion of the investigator, prevents safe surgery/biopsy procedure
The presence of any medical condition that the Investigator deems incompatible with participation in the trial
DONOR: The presence of any medical condition that the Investigator deems incompatible with participation in the trial
Have a history of thrombocytopenia with complications including hemorrhage or bleeding >= grade 2 using NCI CTCAE v4.03, 14 June 2010 that required medical intervention or any hemolytic condition or coagulation disorders that would make participation unsafe in the opinion of the investigator
Has medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
Active infection or antibiotics within one-week prior to study, including unexplained fever; any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial
Any other condition including but not limited to major co-morbidities, which in the opinion of the investigator would render the patient ineligible.
Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol compliance
Presence of serious illnesses or medical condition(s) e.g. brain metastases, systemic infection, heart failure
Inclusion Criteria:\n\n 18 years;\n\n - Clinical confirmation of adrenocortical carcinoma that is locally advanced or\n metastatic and not amendable to surgical resection;\n\n - Failed or declined mitotane (adjuvant or therapeutic) therapy or a platinum-based\n chemotherapy regimen;\n\n - Able to understand and comply with the protocol requirements;\n\n - Willing and able to provide informed consent.\n\n Exclusion Criteria:\n\n - Mitotane level > 5\n\n - Use of contraindicated concomitant medications\n\n - Unstable medical condition that, in the judgment of the investigator, could interfere\n with study procedures or data interpretation.
The risk of rapidly fatal illness and death within 72 hrs, or any concomitant condition not related to ventilator-associated pneumonia that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy
Subjects may not have an underlying medical condition that in the opinion of the investigator could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of dasatinib and ipilimumab in treated subjects
Any medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study Cancer-Specific Exclusion Criteria
Donor must not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation.
Any known preexisting medical condition that could interfere with the subject's participation in and completion of the study such as:
Any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator or co-investigators, could prevent adequate informed consent or compromise participation in the clinical trial
Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, patient with unstable cardiac disease as defined by: Cardiac events such as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; patients with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
Has any condition(s), which seriously compromises the subject's ability to participate in this study, sign consent, or has a known history of poor adherence with medical treatment
Patients who are severely underweight in the opinion of the investigator
Presence of a severe unmanaged psychiatric condition (i.e., psychotic disorder or episode) or a psychiatric condition (e.g., suicidal intent) that would contraindicate safe participation in the study as indicated by the medical chart, treating oncologist, or interactions with the medical/study staff
Has another serious or chronic medical or psychiatric condition that contributes to substantial physical or emotional disability that would detract from participating in either of the intervention programs or from the measurement of intervention outcomes
PATIENTS: Existence of co-morbid disease, which in the opinion of the investigator prohibits participation in the protocol
Have a history of thrombocytopenia with complications including hemorrhage or bleeding of ?Grade 2 per NCI CTCAE v4.03 that required medical intervention or have any hemolytic condition or coagulation disorder that would make participation unsafe in the opinion of the investigator.
Concurrent ocular or intraocular condition that requires medical or surgical intervention to prevent or treat vision loss
Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
Possesses any condition, or is under treatment for any condition which, in the opinion of the investigator and/or consulting physicians(s), may constitute an unwarranted surgical risk
Presence of a severe psychiatric condition (i.e., psychotic disorder or episode) or a psychiatric condition (e.g., suicidal intent) that would contraindicate safe participation in the study as indicated by the medical chart, treating oncologist, or interactions with the medical/study staff
Any current treatment, medical history, or uncontrolled condition, other than malignancy, (e.g., alcoholism or signs of alcohol abuse, seizure disorder, medical or psychiatric condition) that, in the opinion of the investigator, would confound the results of the study or pose any unwarranted risk in administering study drug to the subject
Has been diagnosed with/exhibits any mental neurological disorder/disease/condition that would prevent participation in the study in the opinion of the investigator
In the opinion of the principal investigator (PI) or an associate investigator (AI), the subject has significant cognitive or emotional difficulties that would prevent them from being able to understand and/or participate fully in the intervention or the measures
Subjects with significant concurrent medical complications that in the judgment of the principal investigator(s) could affect the patient's ability to complete the planned trial; there are no therapy restrictions or restrictions regarding the use of other investigational agents
Presence of medical co-morbidities, which, in the opinion of the investigator complicates the surgical procedure or would require additional hospital stay
Medical conditions precluding participation in the intervention or likely to lead to death within 6 months, as determined by the principal investigator (PI)
Either the child or the parent has a mental health or medical condition that, in the opinion of investigators or the treating oncologist, would make it difficult to participate in the study
Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; examples of this would be hearing loss or neuropathy which would prevent tolerance to cisplatin, and paclitaxel administration; the investigator should feel free to consult the Study Chair or Study Co-Chairs for uncertainty in this regard
Presence of a severe psychiatric condition (i.e., psychotic disorder or episode) or a psychiatric condition (e.g., suicidal intent) that would contraindicate safe participation in the study as indicated by the medical chart, treating oncologist, or interactions with the medical/study staff
History of a chronic medical condition that has the potential to significantly impact upper extremity function (e.g. stroke, Parkinson’s disease, multiple sclerosis)
Medical, psychiatric condition which in the investigators opinion will affect the successful completion of study
Known previous or concomitant serious illness (other than advanced cancer with metastatic bone disease) or medical condition, such as, HIV, significant gastrointestinal disease, or cardiovascular event that in the opinion of the investigator may worsen and/or interfere with participation in the study
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's and/or Medical Monitor's judgment, precludes the participants safe participation in and completion of the study
Subject has any clinical condition, diagnosis, or social circumstance that, in the opinion of the Investigator, would mean participation in the study would be contraindicated.
Caregivers: Absence of a serious medical condition likely to influence cortisol assessment in their hair
Participants who, in the judgment the study principal investigator (PI), have severe or unstable mental illness which could interfere with participation in the trial
Subjects with current alcohol use, illicit drug use, or any other condition (e.g., psychiatric disorder) that, in the opinion of the Investigator, may interfere with the subject's ability to comply with the study requirements or visit schedule
Any mental or physical condition, in the opinion of the principal investigator (PI) or PI designee, which could interfere with the ability of the subject to understand or adhere to the requirements of the study
Serious or unstable medical condition that could likely lead to hospitalization during the course of the study or compromise study participation
Self-report or have a medical record of an unstable comorbid medical or psychiatric condition that would make it unsafe or impossible to adhere to the study protocol
Acute or chronic medical disorder that, in the opinion of the investigator or medical monitor, may prevent the subject from completing participation in the study
Any serious, uncontrolled comorbidity or condition that an Investigator believes would interfere with the intent of the study or would make participation not in the best interest of the patient Intraoperative Exclusion Criteria
A medical condition, movement or neurological disorder, or medication use that contraindicates participation in moderate intensity exercise (confirmed by self-report on the Health History Questionnaire, and by physician clearance; if in the professional opinion of the Principal Investigator, Dr. Kerri Winters-Stone, contraindications other than those identified by the patient or physician are present, she may consider the participant ineligible)
Patients must have no significant medical or psychiatric condition that would preclude study completion; tests and exams for this determination should be completed within 28 days prior to registration
Have any medical disease or condition that, in the opinion of the site principal investigator is a contraindication to study participation; this includes any chronic medical condition, defined as persisting 3 months (defined as 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject’s successful completion of this study
Any current treatment, medical history, or uncontrolled condition, other than malignancy, (e.g., alcoholism or signs of alcohol abuse, seizure disorder, medical or psychiatric condition) that, in the opinion of the investigator, would confound the results of the study or pose any unwarranted risk in administering study drug to the subject
Significant unstable medical/psychiatric or substance use disorders, or medically/psychiatrically at risk in the judgment of the study physician (or licensed medical professional designated to consult in his absence) or principal investigator (PI)
Presence of any major medical condition which, in the opinion of the investigator, precludes participation in the study
Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including follow-up), or would interfere with the evaluation of the trial endpoints
Uncontrolled concurrent medical condition likely to limit compliance with the study interventions
Any other medical condition(s) that, in the judgment of the Site Investigator, might interfere with the study or require treatment that might interfere with the study
Subjects with pre-existing medical illnesses or medications which might interfere with the study as determined by principle investigator (PI)
Subjects with any other condition that would contraindicate participation, as determined by the Investigator.
Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible, provided they fulfil the inclusion criteria related to organ system function.
Medical comorbidities that in the opinion of the investigator limits the patient’s ability to complete this study
Subject has significant uncontrolled medical condition within 6 months prior to enrollment, as determined by the investigator.
Significant medical or psychiatric history which would make the participant a poor protocol candidate, in the opinion of the principal investigator, for any aspect of study participation including metformin, unsupervised exercise program or dietary behavior change
Individuals suffering from any unstable medical condition precluding the use of NRT (identified using the Medical History Questionnaire given at baseline)
Have any condition that in the opinion of the investigator would confound the efficacy, safety and tolerability assessments, such as oral thrush.
Positive history of a medical condition that precludes use of the nicotine patch
Serious medical condition (e.g., cancer, heart disease, kidney disease, diabetes)
Any medical condition judged by the investigator to constitute a risk to safe participation
Intercurrent illness or other major medical condition or comorbid condition that might affect study participation (uncontrolled renal, pulmonary or hepatic dysfunction or infection)
A medical condition such as uncontrolled infection or cardiac disease that, in the opinion of the treating surgeon, makes resection unreasonably hazardous for the patient
Subjects with other medical conditions deemed by the principal investigator (or associates) to make the subject ineligible for protocol procedures
Subjects with significant concurrent medical complications that in the judgment of the principal investigator(s) could affect the patient's ability to complete the planned trial, including the multiple imaging studies
Patient/participant has a medical condition which in the judgment of the investigator might make supine positioning for the duration of the scan unsafe, such as (but not limited to) congestive heart failure or significant pulmonary\r\ndisease
Any condition, medical or psychosocial, that in the opinion of the principal investigator would hinder compliance
Patients with psychiatric or other conditions rendering them incapable of participating in informed consent or the requirements of this protocol or other condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete good quality data
Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for protocol procedures
Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for protocol procedures
History of intercurrent or past medical or psychiatric illness that would make participation in a research biopsy protocol difficult or not feasible at the discretion of the principal investigator or co-investigator(s)
Any condition which, in the opinion of the investigator precludes the patient from completion of the study procedure
HEALTHY VOLUNTEER: Any other condition precluding subject participation as per investigator judgment
Any condition which, in the opinion of the investigator, might interfere with study objective
DONOR: Any condition which, in the opinion of the investigator, might interfere with study objective
Patient has any other condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete good quality data
Unstable medical condition, such as ischemic heart disease, or any other disease or medical condition that may place the patient at added risk during the study, as assessed by the Principal Investigator. A patient with a seizure disorder, focal or generalized, not adequately controlled by anti-convulsant therapy, and /or patient who have experienced an event of focal or generalized seizure within 7 days prior to screening will be considered neurologically unstable.
Medical condition uncontrolled by treatment making completion of study unlikely
Patients will be referred by the Urology or Medical Oncology Departments for participation in the study
Medical condition uncontrolled by treatment making completion of study unlikely
Any other condition which in the opinion of the investigator would interfere with successful completion of this clinical trial.
Any other local condition including bacterial superinfection which in the opinion of the investigator would interfere with the efficacy evaluation.
Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for protocol procedures
Subjects with other medical conditions deemed by the principal investigator (or associates) to make the subject ineligible for protocol procedures
Any other condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete good quality data
BIODISTRIBUTION COHORT: Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
DYNAMIC COHORT: Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
No unstable and significant medical conditions as determined by medical history (to ensure safety of the subject, to minimize the effects of poor health on biomarker measures and to maximize compliance to study procedures)
No unstable and significant medical or psychiatric conditions, including lack of stabilization of medications, to be determined by medical history and Prime- doctor of medicine (MD) (to ensure safety of the subject, to minimize the effects of poor health on biomarker measures and to maximize compliance to study procedures)
Having a history or presence of a significant psychiatric disorder or any other condition that, in the investigator’s judgment, would interfere with participation in the trial
Concurrent disease or condition that interferes with participation or safety
Patients suffering from a severe psychiatric disorder or condition that would significantly interfere with study participation
Patients suffering from a severe psychiatric disorder or condition that would significantly interfere with study participation, as determined by the principal investigator or by the attending palliative care physician
Any condition that would in the Investigator's judgment prevents compliance with the requirements of the protocol.
Subjects with any other medical condition, including but not limited to malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study
Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study
Patients with any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results, will not be eligible
Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Have any other medical or psychological condition deemed by the Investigator to likely interfere with the subject's ability to give informed consent or participate in the study.
Has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results
Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
If they have any other condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
Any other medical or psychological condition deemed by the Investigator to be likely to interfere with a subject's ability to give informed consent or participate in the study
Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Any other condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
Any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent or cooperate and participate in the study or with the interpretation of the results
Patients must not have any other condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare or ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Patients with any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results;
If they have any other condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
Have any other medical or psychological condition deemed by the Investigator to be likely to interfere with the subject's ability to give informed consent or participate in the study.
Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Subjects with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study.
Participants with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the participant's ability to sign the informed consent form or his/her ability to cooperate and participate in the study, or to interfere with the interpretation of the results
Subjects with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study.
Patients with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Patients must not have any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient’s ability to give informed consent or cooperate and participate in the study or interfere with the interpretation of the results
Any condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the clinical trial.
Patients with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the patient’s ability to sign the ICF or his/her ability to cooperate and participate in the study, or to interfere with the interpretation of the results
Presence of any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with interpretation of the results
Subjects with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subject to cooperate and participate in the study
Any other medical condition, including mental illness or substance abuse, deemed by the principal investigator to likely interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study
Any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Patients with any other medical or psychological condition deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Any other condition, including mental illness or substance abuse deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate, and participate in the study
Any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or follow up procedures
Any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or follow up procedures
Subjects with any coexisting medical or psychiatric condition which, in the opinion of the investigator likely to interfere with study procedures and/or results
Concurrent medical condition or disease (e.g., autoimmune disease, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in the study
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results
Subject has any concurrent medical condition or disease (eg, active systemic infection, laboratory abnormalities) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results
Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results including uncontrolled severe infections, as well as uncontrolled cardiac disease, or other organ dysfunction; patients with history of tuberculosis, human immunodeficiency virus (HIV) or hepatitis B and C are excluded
Subject has any concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
No serious uncontrolled coexisting medical condition
Any coexisting medical condition precluding full compliance with the study
Any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Any concurrent medical or psychiatric condition or disease (eg, autoimmune disease, active systemic disease, myelodysplasia) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures
Diagnosis of a coexisting medical condition which limits life expectancy to < 2 years
Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Patients must not have any coexisting medical condition that is likely to interfere with study procedures or results, and must be reasonable candidates for intensive chemotherapy, in the opinion of their treating physicians
Medical or psychiatric condition or disease (for example, active systemic disease, uncontrolled diabetes) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results
Participants with any co-existing medical or psychiatric condition that is likely to interfere with study procedures and/or results
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results
Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
Any other medical history, including laboratory results, deemed by the investigator likely to interfere with their participation in the study, or to interfere with the interpretation of the results
Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results
Any other medical issue, including laboratory abnormalities, deemed by the Investigator to be likely to interfere with patient participation
Any other medical history, including laboratory abnormalities, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results
Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator’s opinion would be likely to interfere with a patient’s participation in the study, or with the interpretation of the results
Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
Patients with medical conditions that compromise their ability to complete the study or confound interpretation of study results
Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history that, in the Investigator's opinion, would likely interfere with the person's study participation or the interpretation of his or her results.
Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results.
Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results
Patients with serious illnesses, medical conditions, or other medical history, including a prior history of pericarditis/pericardial effusion, or abnormal laboratory results, which, in the investigator's opinion, would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
History of other malignancies in the last 5 years, in particular those that could interfere with interpretation of results.
Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
FOLFIRI therapy is appropriate for the patient and is recommended by the Investigator.
For inclusion into optional exploratory genetic and biomarker research, patients must fulfill the following criteria:\r\n* Provision of informed consent for genetic research\r\n* Provision of informed consent for biomarker research\r\n** If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient; the patient will not be excluded from other parts of the study
The patient must have undergone either a mastectomy (total, skin-sparing, or nipple-sparing) or lumpectomy
Patient has undergone total resection of the primary tumor with curative intent\r\n* NOTE: Patient is to be pre-registered to screening (Step 0) and tissue submitted to Foundation Medicine as soon as possible after surgery in order to meet the 8 week deadline to register the patient to Step 1 after surgery; full assay minimum turn-around time is 17-24 days
Surgical formalin-fixed paraffin-embedded (FFPE) specimen must be available for submission to GenomeDx for genomic analysis on DECIPHER GRID platform\r\n* Please note: If a patient already has a Decipher risk score and meets all of the other eligibility criteria, the patient is eligible to be registered; however, the Decipher risk report will need to be submitted to GenomeDx for validation
Although they will not be considered formal eligibility (exclusion) criteria, physicians should recognize that the following may seriously increase the risk to the patient entering this protocol:\r\n* Psychiatric illness which would prevent the patient from giving informed consent\r\n* Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient\r\n* Patients with a “currently active” second malignancy other than non-melanoma skin cancers; patients are not considered to have a “currently active” malignancy if they have completed therapy and are free of disease for >= 3 years; there is an exception for patients with a history of well differentiated thyroid cancer that has progressed to anaplastic thyroid cancer\r\n* Patients who cannot swallow oral formulations of the agent(s)\r\n* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study ; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)\r\n* Efatutazone is metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), and inhibits CYP2C8, 2C9, 2C19, and 3A4, and is a substrate of P-glycoprotein (PgP) and breast cancer resistance protein (BCRP)
Patient must have chemosensitive disease as defined by at least a partial response to salvage therapy at their latest assessment
As of Amendment 2, if the registering site is a photon center (registering patients to group I), the patient must agree to participate in the advanced imaging sub-study
Patient must have undergone extended surgical staging including mediastinoscopy or endobronchial ultrasound; at minimum, samples must be obtained from the mediastinal stations 4R, 7 (subcarinal), and 4L; this surgical staging must be performed within 42 days prior to step 1 registration; patient must be T1-3 and N0-N2 (single station)
Patient may have discontinued RT early due to toxicity or other reasons
If the patient is a primary English speaker, the patient must participate in the NCF and patient reported outcomes part of the study; if the patient is a primary French or Spanish speaker, the patient must participate in the patient reported outcomes part of the study
In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy\r\n* Clinical situations in which emergent treatment may be indicated include, but are not limited to, the following circumstances:\r\n** Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)\r\n** Uncorrectable coagulopathy\r\n* For a patient to maintain eligibility for AHEP1531 when emergent treatment is given, the following must occur:\r\n** The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility criteria at the time of emergent treatment\r\n** Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP1531 enrollment\r\n* Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
Relevant diseases or clinical situations which may increase the patient's risk
For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria:\r\n* Patient is in second salvage or more and B1931022 has been considered and ruled out as a treatment option; OR\r\n* Patient was treated on the standard of care arm of B1931022 and failed therapy
Hospitalization for an acute medical issue within 4 weeks prior to screening visit that would otherwise not be managed in an infusion center or outpatient clinic setting (i.e., a patient admitted to complete a transfusion would not be ineligible)
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Patient with angina not well-controlled by medication;
Patient declines participation in NANT 2004-05, the NANT Biology Study
If cardiorespiratory abnormalities are identified, please refer the patient to his managing physician for further assessment and diagnosis.
RER is not a criteria of the test. This objective measure should only be used to assist practitioners with patient management and decision-making.
If sexually active male, patient must:
The patient and/or the patient’s legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained, in accordance with institutional policies approved by the U.S. Department of Health and Human Services
PIK3CA WILD TYPE COHORT (closed 03/17/2016): If premenopausal, patient must be willing to comply with pregnancy requirements
Patient intolerant to imatinib
Post randomization exclusion will occur if the patient is found to have unresectable disease at laparotomy and therefore will not have the potential for the same post-operative complications
Non-cooperative behavior or non-compliance of the patient and/or of his/her family
Patients with leiomyosarcoma must have tumors with intact Rb as documented by protein expression by immunohistochemistry (IHC) for study entry; patients without sufficient archival tissue for testing will not be eligible; in the event that a patient has prior sequencing information (i.e. through commercial testing) suggestive of intact Rb, the patient may be included into the study on a case by case basis as determined by the principle investigators; the patient will still be required to submit tissue for Rb determination by IHC, but will not need to wait for these results for study entry
Patient is pregnant or breastfeeding, or plans to become pregnant or father children from time of signing consent and lasting until 6 months after the last dose of trial treatment
Patients will be strongly encouraged to participate in 10-C-0086; if a patient does not agree to enroll on 10-C-0086, germline genetic analysis will not be performed
Confirmation that the patient’s health insurance will pay for the treatment in this study (patients may still be responsible for some costs, such as co-pays and deductibles); if the patient’s insurance will not cover a specific treatment in this study and the patient still wants to participate, confirmation that the patient would be responsible for paying for any treatment received
Patient must sign informed consent form to indicate patient's understanding study's purpose and procedures and willingness to participate. Should patient be incapable of giving consent, the patient's legally authorized representative (as defined by local regulation) must give consent. However, should patient, in any manner, choose not to participate this takes precedence and will be respected.
Depending on the stage of the protocol, pathway activation based on p-S6 will need to be done in real time to assess if patient is eligible
Willingness and ability of participants to use the electronic device to report selected study outcomes; Caregivers and site staff can assist with patient diary input but patient must be able to independently comprehend and answer the questionnaires
For inclusion in optional genetic research, the patient must provide a written informed consent for genetic research.
Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
Patient selected to undergo Whipple procedure or distal pancreatectomy
Any patient with an open oral ulceration(s) should avoid dosing with AZD4635 oral suspension.
Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and/or requirements.
Other medical or surgical conditions, especially involving the cardiac, respiratory, renal or hepatic organ systems that would either be unsafe for the patient, would limit study participation, or that would impede the determination of causality of any adverse events experienced during the conduct of this study.
The patient is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids.
Disease status: patients with malignancy are to be referred in remission for evaluation, except in cases of virus-associated malignancy who may be referred at any time; should a patient have progressive disease or a donor becomes unavailable after enrollment, the patient will be referred back to his/her primary hematologist-oncologist for treatment; if this course of action is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease under the current study, although this should only occur as a bridge to transplant; if under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off the study; patients receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
General poor health, multiple co-morbidities placing the patient at risk or otherwise unsuitable for trial participation
Patients who have a history of another primary malignancy from which the patient has been disease free for < 3 years at the time of enrollment, with the exceptions of: a patient with a familial cancer syndrome-associated NETs including MEN1, VHL, NF-1, and thymidylate synthetase (TS)
Patients with a \currently active\ second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patient is more than 6 months since the last dose of FOLFIRI
Post exploratory thoracotomy must be done > 3 weeks prior to study registration or patient did not have post exploratory thoracotomy.
Women with post-surgical temporary breast expanders will require individual assessment. Depending on the manufacturing product and other treatment planning-specific details the patient may be eligible or may be deemed ineligible, as determined by treating investigator.
Patient must not have any active infection or concurrent illness obscuring toxicity or dangerously altering drug metabolism
For Cohorts 1, 3 and 4, contraindication to chemotherapy as first-line therapy due to patient age, comorbidity or patient preference
Patient's medical history does not contraindicate treatment with at least one of the following antibiotics: ampicillin, clindamycin and erythromycin/clarithromycin.
Patient must have a primary medical or surgical oncologist in the community or at NCI who is willing to collaborate with the ROB staff in the clinical management of the patient
Patient re-enrollment: This study permits the re-enrollment of a patient that has discontinued the study as a screen failure (ie, patient has not been dosed/has not been treated); if re-enrolled, the patient must be re-consented and satisfy all eligibility criteria
At time of registration and within 4 weeks prior to initiating on-protocol treatment: Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L\r\n* May be waived on a case-by-case basis for patient populations recognized to have normal baseline values below this level.
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
If a patient engages in sexual intercourse with a woman of childbearing potential, a condom and another form of birth control must be used during and for 100 days after completing treatment with CORT125281 or enzalutamide. A condom is required during and for 100 days after completing treatment with enzalutamide if a patient is engaged in sexual activity with a pregnant woman. Patients must also agree to avoid sperm donation during the study and for at least 100 days after the final treatment administration.
The patient has a contra-indication for using a CPAP device.
The patient is uncooperative.
The patient has reduced consciousness.
The patient has sustained trauma or burns to the face.
Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement
The patient has untreated concurrent urothelial cancer in other locations other than the target area (unless treated during screening)
Patient must have metal stent in place if duodenal stent is required. If patient has plastic stent, this must be replaced prior to radiation.
Patient's indication is commercially available and reimbursed in the local country.
Patient has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication.
Patient currently has unresolved toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study.
Patient must receive the following medical regimen as part of standard of care immunoprophylaxis for GvHD in either study arm at doses and regimen determined by local institutional guidelines, physician preference, and patient need: MTX or MMF + calcineurin inhibitor (CSA or TAC) +/- ATG (ATG use is limited to 30% of patients).
Any other condition that would cause a risk to the patient if he/she participated in the trial.
Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this clinical study protocol, so long as they consent to that part.
Patient has poorly controlled hypertension and on multiple antihypertensives
Patient has a history of interstitial cystitis
Mental condition that prevents patient from performing the study activities and requirements
Patients must not have current evidence of any condition, therapy, or laboratory abnormality (including active or uncontrolled myelosuppression [ie, anemia, leukopenia, neutropenia, thrombocytopenia]) that might confound the results of the study or interfere with the patient's participation for the full duration of the study treatment or that makes it not in the best interest of the patient to participate
Patient is or will be enrolled on protocol 00-CH-0093, Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma
Must have outside endocrinologist/medical oncologist who can follow the patient after receiving peptide receptor radionuclide therapy (PRRT) at the NIH
Patient must have no active major medical or psychosocial problems that could be complicated by study participation
Patient has sufficient stored T cell product to manufacture appropriate doses of T-APCs
Patient with a history of genetic prothrombotic state
Availability of and patient acceptance of curative therapy
Non-English speakers will be excluded from participating in the patient-reported outcomes component of the study.
Patient on Coumadin and not willing to change to LMWH or oral Factor II or Xa inhibitor with half-life of less than 24 hours.
If a patient declines to participate in genetics research, there will be no penalty or loss of benefit to the patient; a patient who declines genetics research participation will not be excluded from any other aspect of the main study
Availability of and patient acceptance of curative therapy
Prior treatment with everolimus is allowed, if the patient was able to tolerate 10 mg daily everolimus with acceptable side effects, and if everolimus was not given in combination with fosbretabulin; a 1 week washout period will be required if patient was previously on everolimus
Any reason, at the investigator’s discretion, that the participation of the patient in this protocol would not be in patient’s best interest, or where the patient would be unable to adhere to the study requirements
The patient must have received a boost immunization with trivalent inactivated poliomyelitis (IPOL) (Sanofi-Pasteur) at least 1 week prior to administration of the study agent
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements
Patient on anti-retroviral medications
Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible
No known infection with HIV. Due to the mechanism of action of ipilimumab, activity and side effects in an immune compromised patient are unknown.
Patients on concurrent anti-cancer therapy, unless specifically agreed to by the patient's medical oncologist and consenting professional
Patient is receiving any azole.
Patient is currently participating in an Immunocore-sponsored study of IMCgp100 and is actively receiving IMCgp100. Patient must have fulfilled all required assessments in the parent study (unless the study is being terminated)
Patient has demonstrated compliance with the parent study requirements, as assessed by the principal investigator and patient is able to comply with the necessary visits and assessments as part of the rollover study
Patient has been permanently discontinued from any IMCgp100 study or from IMCgp100 treatment in the parent study due to unequivocal progressive disease, unacceptable toxicity, non-compliance to study procedures, withdrawal of consent, or any other reason
Patient must have a graded prognostic assessment (GPA) score 0.5 or greater
Confirmed availability of production capacities for the patient's ACTolog products.
Patient must be a candidate for SBRT to at least one intrahepatic lesion; there is no limit on the number of intrahepatic lesions the patient may have
In accordance with National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) policy, protocol treatment is to begin within 2 working days of patient registration
Patient on anti-retroviral medication (as these medications may alter patient metabolism)
The expression of WT1 in the patient’s peripheral blood and/or bone marrow will be determined; if WT1 expression in the patient specimen is within the normal physiologic range or is not detected, the patient will be ineligible for treatment with WT1-specific T cells (and will not be included in the observation cohort)
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer
Inoperable disease because of patient refusal, neurosurgical evaluation, or any other medical reasons
Multidisciplinary evaluation of the patient must be performed with a consensus recommendation for reirradiation
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patient must be able to maintain a 30 second breath hold
Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug
Patient may have been pretreated with intermediate to high dose cytarabine (more than 1000mg/m2/d over 5d) if the day of the last infusion was at least 90 days before inclusion in the study
psychiatric conditions e.g. patients unlikely to comply with the protocol, e.g. mental condition rendering the patient unable to understand the nature, scope, and possible consequences of participating in the study
Patient has received intervening therapy for lymphoma after CTL019 infusion
Patients have unresectable MPM or the patient refuses surgery for resectable MPM
This study permits the re-enrollment of a patient who has discontinued the study for a reason other than treatment failure or adverse event(s) of the study treatment; the patient must be re-consented and assigned a new subject number
Investigator does not believe study participation, for any reason, is in the best interest of the patient
Patient and partner are willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer.
Any other disease, either metabolic or psychological, that as per Investigator assessment may affect the patient's compliance or place the patient at an increased risk of potential treatment complications.
Patient must be able to have gold fiducial markers placed in the prostate or, if patient already has fiducial markers placed, they must be in accordance with the protocol specifications
The patient is eligible for TSEBT
Localized EAC and its baseline clinical stage determined as: T2-T3N0 or T1-3N positive (+); imaging studies suspicious for metastases must be followed with a negative biopsy before a patient can enter the study
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
Have biopsiable disease; if biopsy is attempted and unsuccessful (the patient undergoes an invasive procedure), the patient may still be treated
Young patient age between 12 – 15 could be included in only 6 centers (Bordeaux, Lyon, Villejuif, Lille, Marseille and Paris)
Willingness to take varenicline OR nicotine patch (patient choice)
Patient is mentally or legally incapacitated at the time of the study
Patient eligible for SABR to the IVC tumor thrombus as decided by the treating radiation oncologist
Patient eligible for IVC tumor thrombectomy as decided by the treating urologist
Patient must have injectable disease (direct injection or ultrasound guided)
Patient must have no active major medical or psychosocial problems that could be complicated by study participation
Patient must have no active major medical or psychosocial problems that could be complicated by study participation
Patient has completed participation in one of the ONC201 protocol, has not shown tumor progression while on study treatment, and has tolerated the study drug without unacceptable toxicities
Patient has not met criteria for withdrawal from the base protocol
Confirmation by a surgeon that the patient is able to undergo a low anterior resection with total mesorectal excision =< 28 days prior to registration
Patient will have opted for SBRT among definitive treatment choices
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
Unreliable for follow-up (drug use, planning to move out of region ,etc.); any patient that lives more than 100 miles away will be excluded
Imaging studies show evidence of recurrent tumor(s); if a patient is going to be enrolled to dose level two or higher, the patient must have a component of supratentorial disease (so as to enable placement of a Rickham reservoir/catheter) that is amenable to resection or biopsy
Infiltrative form of HCC on imaging; if there is at least one measurable lesion per modified RECIST (mRECIST) criteria and otherwise patient is eligible for the study, the patient can be enrolled
Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease
One of the following must be satisfied:\r\n* The patient is undergoing mobilization to collect and store for an autologous PBSC transplant in the future\r\n* The patient is eligible to undergo autologous PBSC transplantation on institutional protocols in the future
Patient not candidate for orthotopic liver transplantation at the Hospital of the University of Pennsylvania based on review of patient imaging and history at multidisciplinary Hepatic Tumor Conference at the Hospital of the University of Pennsylvania
The patient is allergic to naproxen or ibuprofen
If younger than 40, there must be comorbidities which preclude the patient to undergo cyclophosphamide (Cy) TBI conditioning regimen
Inclusion criteria at the time of Procurement:\n\n - Patient with malignant or nonmalignant diseases who are candidates for transplant.\n\n - Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA\n class I (serological) and II (molecular) antigens.\n\n Inclusion criteria at the time of CTL infusion:\n\n - Recipients of at least one unmanipulated cord blood unit fractionated into 2 fractions\n (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with\n CMV/Adenoviral disease or reactivation.\n\n - Lansky/Karnofsky scores >60\n\n - Absolute neutrophil count (ANC) greater than 500/ul.\n\n - No evidence of GVHD > Grade II at time of enrollment.\n\n - Life expectancy > 30 days\n\n - Absence of severe renal disease (Creatinine > x 3 normal for age)\n\n - Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x\n upper limit of normal.\n\n - Patient must be at least 30 days post transplant to be eligible to receive CTL\n\n - Written informed consent and/or signed assent line from patient, parent or guardian.\n\n - Patient not on Fi02 of >60%\n\n Exclusion criteria at the time of Procurement\n\n - Pregnant or lactating\n\n - Patients with active central nervous system disease\n\n - Patients with Karnofsky performance status <70%\n\n - Patients with grade 3 or 4 or primary myelofibrosis\n\n - Patients with suitable related donors\n\n Exclusion criteria at the time of CTL infusion\n\n - Pregnant or lactating\n\n - Unable to wean steroids to ?0.5 mg/kg/day prednisone.\n\n - Patients with other uncontrolled infections (except CMV and/or adenovirus and/or\n EBVemia).\n\n - Patients with less than 50% donor chimerism in either peripheral blood or bone marrow\n or patients with relapse of original disease.
Patient must be eligible for HD IL-2 treatment
RECIPIENT: Patients are to be referred in remission for evaluation; should a patient have progressive disease, or a donor becomes not available after enrollment, the patient will be referred back to their primary hematologist-oncologist for treatment; if this course of action is not in the best interest of the patient according to the clinical judgment of the principal investigator (PI)/lead associate investigator (LAI), then the patient may receive standard treatment for the malignant disease under the current study; if under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol
Patient is currently benefiting from the treatment with pasireotide, as determined by the investigator
Patient has demonstrated compliance, as assessed by the investigator, with the parent study requirements
Patient has been permanently discontinued from pasireotide study treatment in the parent study due to unacceptable toxicity, non-compliance to study procedures, withdrawal of consent or any other reason
Patient has participated in a Novartis sponsored combination trial where pasireotide was dispensed in combination with another study medication and is still receiving combination therapy. (only patients receiving pasireotide monotherapy can be included)
Subjects who experience a significant flare after discontinuation of a tumor necrosis factor (TNF) inhibitor as part of this study that requires urgent medical management or hospitalization, or in the estimation of the principal investigator poses excessive risk to the patient to enter the study
Must be a patient to be treated with SBRT only at Johns Hopkins Hospital
Patient must be able to have fiducials placed; if not, the tumor must be posterior and adjacent to the aorta and treatment will only be permitted at the discretion of the principal investigator
Patient must be able to drink and eat more than 75% of their usual daily meals
Patient has signed the informed consent document agreeing to the use of the study drug, domperidone
Patient refusal
Patient agrees that intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
Patient has any disease that will obscure toxicity or dangerously alter drug metabolism
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patient must live within 30 minutes of the treating physician’s office during outpatient treatment
Any patient with hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied; patients treated on this protocol will be without morphological evidence of disease, or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemo-responsive
Patient must be able to swallow enteral medications; patient must not require a feeding tube; patient must not have intractable nausea or vomiting, gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, or uncontrolled inflammatory bowel disease (Chron’s, ulcerative colitis)
For clinically stage II patients, the patient must have been evaluated by a thoracic surgeon, and deemed medically or technically inoperable, or the patient must refuse surgery
Patients with malignancy are to be referred in remission for evaluation, except in the case of viral associated malignancies; should a patient have progressive disease or a donor becomes unavailable after enrollment, the patient will be referred back to their primary hematologist-oncologist for treatment; if this course of action is not in the best interest of the patient according to the clinical judgment of the principal investigator (PI)/lead associate investigator (LAI), then the patient may receive standard treatment for the malignant disease under the current study; if under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol
Patients should have uncontrolled intercurrent illness, which in the opinion of the attending medical oncologist, would render the patient unsuitable for the study (i.e., preclude safe administration of the prescribed chemotherapy treatment).
The donor and the patient and/or the patient’s legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policy approved by the United States (U.S.) Department of Health and Human Services
Patient who is otherwise considered unsuitable for transplant at the discretion of the principal investigator
The patient and/or the patient's legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policies approved by the United States (U.S.) Department of Health and Human Services; informed consent must be signed prior to registration on study
Presence of the t(9;22) (q34;q11) or bcr-abl fusion in the leukemic cells (if data are not known, patient still may be eligible)
Patient is unlikely to comply with study procedures, restrictions and requirements and judged by the Investigator that the patient is not suitable for participation in the study.
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
Protocol treatment is to begin within 5 working days of patient enrolment.
not completed treatment as defined in the base protocol for reasons that are not considered critical and unmanageable for the safety of the patient (as evaluated by the investigator and/or the sponsor) and the patient clearly showed response of PR or better.
Patient has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements.
Patient is currently benefiting from treatment with everolimus, as determined by the guidelines of the parent protocol.
Patient has been permanently discontinued from everolimus study treatment in the parent study.
Patient is currently enrolled in a Novartis-sponsored, Oncology Clinical Development & Medical Affairs study receiving imatinib and has fulfilled all their requirements in the parent study. 2.Patient is currently benefiting from the treatment with imatinib, as determined by the investigator. 3. Patient has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements.4. Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures. 5. Written informed consent obtained prior to enrolling in roll-over study.
Patient has been permanently discontinued from imatinib treatment in the parent study due to unacceptable toxicity, non-compliance to study procedures, withdrawal of consent or any other reason.
Patient has participated in a Novartis sponsored combination trial where imatinib was dispensed in combination with another study medication and patient is still receiving combination therapy.
Inclusion Criteria:\n\n -Patient is currently enrolled in a Novartis-sponsored, Oncology Clinical Development &\n Medical Affairs study receiving nilotinib and has fulfilled all their requirements in the\n parent study -Patient is currently benefiting from the treatment with nilotinib, as\n determined by the investigator -Patient has demonstrated compliance, as assessed by the\n investigator, with the parent study protocol requirements -Willingness and ability to\n comply with scheduled visits, treatment plans and any other study procedures -Written\n informed consent obtained prior to enrolling in roll-over study\n\n Exclusion Criteria:\n\n - Patient has been permanently discontinued from nilotinib treatment in the parent study\n due to unacceptable toxicity, non-compliance to study procedures, withdrawal of consent or\n any other reason - Patient has participated in a Novartis sponsored combination trial where\n nilotinib was dispensed in combination with another study medication and patient is still\n receiving combination therapy -Patients who are currently receiving treatment with any\n medications that have the potential to prolong the QT interval or inducing Torsade de\n Pointes and the treatment cannot be either safely discontinued at least one week prior to\n nilotinib treatment or switched to a different medication prior to start of nilotinib\n treatment and for the duration of the study -Pregnant or nursing (lactating) women, where\n pregnancy is defined as the state of a female after conception and until the termination of\n gestation, confirmed by a positive hcG laboratory test. -Women of child-bearing potential,\n defined as all women physiologically capable of becoming pregnant, unless they are using\n highly effective methods of contraception during the study and for 30 days after the final\n dose of nilotinib.
Patient refractory to dacarbazine defined as patient presenting a disease progression after 3 months of dacarbazine therapy.
Patient presenting with at least one of the following feature: ischemic heart disease, cardiac failure, conduction disorders or arrythmia
Naïve patient or patient previously treated with imatinib as neoadjuvant/adjuvant who relapsed after imatinib discontinuation
Patient who are receiving concurrent combination with sorafenib (Nexavar) and TACE (transarterial chemoembolization) in their originating study will be eligible.
Patients who have completed the End of Treatment assessments in their originating study. Every effort should e made to conduct the End of Treatment visit such that the patient does not have any interruption in sorafenib dosing.
Inclusion Criteria:\n\n - • Patient has a non-palpable breast lesion that requires excision\n\n - Lesion depth ? 3 cm from the skin surface in the supine position\n\n - Patient is scheduled for excision or BCT at a participating institution\n\n - Patient is between the ages of 18 and 90 years\n\n - Patient is female\n\n - Patient is willing and able to comply with all study procedures and be available\n to follow-up for the duration of the study\n\n - For lesions requiring multiple reflectors for localization, they must allow for\n reflectors to be placed ? 1cm from one another relative to the coronal plane\n Subject Exclusion Criteria\n\n An individual who meets any of the following criteria will be excluded from participation\n in this study:\n\n - Patient had a previous ipsilateral breast cancer\n\n - Patient has multicentric breast cancer\n\n - Patient has Stage IV breast cancer\n\n - Patient has been treated with neoadjuvant chemotherapy\n\n - Patient is pregnant or lactating\n\n Exclusion Criteria:
Patient declines participation in NANT 2004-05, the NANT Biology Study
Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements
Patient is anticipated to continue for at least 28 days with an EGFR inhibitor or restart ? 14 days of registration and continue for at least 28 days
Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed)
Patient has a foreign body which in the opinion of the treating investigator could be difficult to manage in case of infection
The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient’s health and survival, than of the MCL, within the subsequent 6 months at the time of consent.
FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Reasonable expectation that the patient can wait 3-6 months for generation of data for subsequent treatment selection.
FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH STANDARD OF CARE (PART 2): The patient condition remains suitable for the selected therapy. If the patient receives prior therapy with a given agent (X) and progressed, but the testing in Part 1 found this agent to be effective in a combination, the patient remains eligible for this combination that includes agent X.
THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: PDX data are non-informative.
THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: Part 1 data contradict clinical judgment. The investigator should discuss with the principal investigator (PI) and use the best discretion.
It will be at the Principal Investigator's (PIs) discretion to enroll a patient who has a small, asymptomatic brain hemorrhage, but patients who have had symptomatic hemorrhages will be excluded
Patient is premenopausal defined as either:
Patient had last menstrual period within the last 12 months or
Patient must have:
Respiratory illness requiring hospitalization at the time of step 1 registration\r\n* Note: if the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patient must be able to swallow capsules and have no surgical or anatomic condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis
Patients who speak English (or read one of the languages for which a translation is available must consent to complete the mandatory dysphagia-related patient reported instrument (MDADI); if the patient cannot understand spoken English and reads only languages not available in the MDADI translations, the patient can still participate in the trial, as this has been factored into the trial statistics; for all other patients, the MDADI is mandatory as it is included in the primary endpoint to be studied
Patient is allergic to 5-FC, leucovorin, or 5-FU
Patient has had prior therapy with neural stem cells
Patient must be tolerating oral intake
Patient agrees that intravenous (IV) bisphosphonates will be withheld during the first 8 weeks of dasatinib therapy due to risk of hypocalcemia
Patient must not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
Donors: If a patient is homozygous at a particular loci, mismatching at that loci is not allowed due to an isolated graft rejection vector, i.e., patient A*0101 and the donor is A*0101, A*0201; such a mismatch may increase the risk of graft rejection; if patient and donor pairs are both homozygous at a mismatched loci, they are considered a two-HLA antigen mismatch, i.e., the patient is A*0101 and the donor is A*0201, and this type of mismatch is not allowed
Potential patients referred for the study may not be eligible for the experimental protocol therapy due to reasons such as uncertainty about donor HLA typing or need to control malignant disease, infection, or metabolic abnormality such as hypercalcemia on an emergent basis; should a referred patient present to us in such a scenario, the patient will be referred back to their primary hematologist-oncologist for treatment; however, if referral back to the referring physician is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease or complicating conditions (infection, metabolic problems) under the current study; in other cases, a patient may have reasonable control of malignancy but does not meet the CD4 cell cut-off of 100 cells per microliter required for cohort 3 therapy (or, absolute lymphocyte count [ALC] value of < 300); in such cases, standard care chemotherapy regimens may be administered for the specific goal of reducing the CD4 count (that is, immune depleting regimens such as the pentostatin plus cyclophosphamide combination, administered similar to the manner that we have developed on protocol 08-C-0088); if it becomes apparent that the patient will not be able to proceed to experimental therapy, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol; because such standard care therapy is not experimental, it is not necessary to complete the eligibility criteria prior to receiving such standard care; however, prior to initiation of the experimental therapy, the patient must meet each of the eligibility criteria detailed above; attempts will be made to standardize such pre-transplant chemotherapy (by administration of EPOCH-FR chemotherapy); however, other regimens using approved agents will be allowed if such regimens are thought to be in the best interest of the patient
Any other concurrent illness which in investigator’s opinion puts the patient at excessive risk of treatment related toxicities
Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
Operative report or other source documentation in the patient record
Patient has identified PIK3CA status
Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment
Patient must be planning to undergo complete cytoreduction of all peritoneal disease
No or minimal disease-related symptoms not affecting patient daily activities.
Before starting therapy the patient should be able to maintain adequate oral nutrition of >= 1500 calories estimated caloric intake per day and be free of significant nausea and vomiting
If surgical margin status cannot be determined after consultation with the operating surgeon and the institutional pathologist, the patient will be ineligible
Patient has been permanently discontinued from ribociclib (LEE011) in the parent protocol for any reason.
Patient meets all sub-protocol specific criteria of each applicable sub-protocol
Before enrolling a patient, the institution must verify the availability of an adequate supply of methotrexate for a full course of therapy
Known peripheral neuropathy > grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
Main inclusion criteria:\n\n 1. Female patient, with histologically or cytologically confirmed advanced / metastatic\n epithelial ovarian cancer either :\n\n - refractory to first line platinum treatment (defined as progressive disease while\n receiving or persistent disease after platinum-based therapy, according to GOG),\n or\n\n - candidate to third line treatment.\n\n 2. Patient has recovered of all acute toxic side effects of prior therapy or surgical\n procedures to grade ?1 National Cancer Institute-Common Toxicity Criteria (NCI-CTCAE\n v4.02), except for the laboratory values\n\n 3. Patient has at least one target lesion that can be measured in one dimension,\n according to the Response Evaluation Criteria in Solid Tumors (RECIST)\n\n 4. ECOG Performance status ? 2\n\n 5. Patient with adequate organ function per laboratory tests evaluations\n\n 6. Patient with life expectancy > 3 months\n\n 7. Patient weight > 40 kg and BMI > 18\n\n 8. Female patient ? 18 years\n\n 9. Patient with nutritional risk index (NRI) ? 83.5, i.e. with no or moderate\n malnutrition;\n\n 10. Female patient of childbearing potential (entering the study after a menstrual period\n and who have a negative pregnancy test), who agrees to use two methods (one for the\n patient and one for the partner) of medically acceptable forms of contraception during\n the study and for 3 months after the last treatment intake.\n\n Main exclusion criteria:\n\n 1. Patient intolerant to gemcitabine\n\n 2. Patient who has not recovered from any significant treatment toxicities prior to\n baseline (?Grade 2)\n\n 3. Patient presenting with serious cardiac disorders defined in the protocol\n\n 4. Pregnant or nursing female patient\n\n 5. Patient with active central nervous system (CNS) metastasis or with history of CNS\n metastasis\n\n 6. Patient treated for a cancer other than epithelial ovarian cancer within 5 years\n before enrolment, with the exception of basal cell carcinoma or cervical cancer in\n situ\n\n WASH-OUT:\n\n 1. Patient is at least 4 weeks from any major surgery (at baseline/W0)\n\n 2. Patient treated with any investigational agent within 4 weeks prior baseline\n\n 3. Patient who had systemic chemotherapy within 4 weeks before baseline\n\n 4. Patient who had radiotherapy within 4 weeks before baseline
Any reason that, in the opinion of the Investigator, contraindicates that the patient participates in the study
A signed Patient Authorization Form (HIPAA) has been obtained prior to registration
Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
All infections must be resolved and the patient must remain afebrile for seven days without antibiotics prior to being placed on study
household contact with hepatitis B infected patient(s),
household contact of hepatitis C infected patient(s),
Active hepatitis B, unless patient has been on antiviral agents for at least 2 months (baseline testing not required)
Patient with baseline symptoms of incontinence defined as urine leak in any of the following circumstances: 20.1. Before the patient can get to the toilet 20.2. When coughing or sneezing 20.3. While being asleep 20.4. While being physically active/exercising 20.5. After finishing urinating and being dressed 20.6. Leaking for no obvious reason
Patient with baseline impotence scoring 17 or below in the IIEF-5 (SHIM) questionnaire
The participating urologist judges that the standard next therapy, based on present urologic guidelines for this patient, is radical cystectomy
In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled on AHEP0731 without a biopsy\r\n* Clinical situations in which such emergent treatment may be indicated include, but are not limited to, the following circumstances:\r\n** Anatomic or mechanical compromise of critical organ function by tumor (eg, respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc)\r\n** Uncorrectable coagulopathy\r\n* For a patient to maintain eligibility for AHEP0731 when emergent treatment is given, the following must occur:\r\n** The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alpha fetoprotein, and must meet all AHEP0731 eligibility criteria at the time of emergent treatment\r\n** Patient must be enrolled on AHEP0731 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP0731 enrollment\r\n** If the patient receives AHEP0731 chemotherapy PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements; Note: Patients who are likely to require surgery or radiation for NF2-related tumors during the first year of treatment in the investigator’s opinion should not be enrolled on this clinical trial
Patient has score of 0 or 1 on the neurotoxicity evaluation, as determined by the healthcare provider
Patient has or has ever had
Patient has a history of interstitial cystitis.
Pregnancy; patient attestation that they are not pregnant will be acceptable as per standard policy for MRIs at Dartmouth Hitchcock Medical Center (DHMC)
Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy.
The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient’s health and survival, than of the MCL, within the subsequent 6 months at the time of consent; investigator discretion is allowed
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Standard chemotherapy/trastuzumab declined by patient OR patient is deemed by physician for any reason to not be a candidate for standard therapy (i.e. patient and/or provider choose not to pursue standard trastuzumab-based chemotherapy regimen because of concerns related to toxicity or patient preference)
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
Patient has evidence of uncontrolled malabsorptive diarrhea that would prevent adequate absorption of PBI 05204.
Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded; patient should have complete resolution of their systemic disease not requiring additional systemic therapy (e.g. maintenance rituximab or Decadron)
Patient is mentally or legally incapacitated at the time of the study
The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient’s health and survival, than of the MCL, within the subsequent 6 months at the time of consent; investigator discretion is allowed
Patient has valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
As judged by the investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
Patients who cannot undergo staging laparoscopy; for example, this may include patients with a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or potentially harmful; the patient is eligible if they have a common bile duct stent adjacent to the tumor that may be used as an internal marker, or if the patient has already had a staging laparoscopy without marker implantation and the markers can be implanted (by interventional radiology) prior to the beginning of radiation therapy
Patient has up to 6 local pulmonary metastases targetable by cryoablation.
Genetic disorder predisposing patient to skin cancers or radiation sensitivity (basal cell nevus syndrome, xeroderma pigmentosum, ataxia telangiectasia mutans)
Patients must have been surgically or medically castrated; if the patient is being treated with medical castration, he must be willing to continue this treatment for the duration of the study; ADT should not be initiated, terminated, or dose-adjusted during the study
The patient must be discussed at GI Tumor Board, NCI and suitability for the interventional procedure (TACE or RFA) re-affirmed
Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease
Patient may not be receiving any other antineoplastic agents (hydroxyurea is allowed)
Patient must NOT have absorption issues that would limit the ability to absorb study agents
For subjected enrolled in the United States, no coverage or not-acceptable by patient co-pay for lenalidomide
Patient is eligible for Low-Dose Cytarabine (LDAC) treatment.
Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
Patient has documented MR4.5 at the time when switched from imatinib to nilotinib
Patient ever attempted to permanently discontinue imatinib or nilotinib treatment
Patient must not have a true unknown primary in which permanent section results are negative for malignancy in completely excised ipsilateral oropharyngeal tissue (palatine and lingual tonsil)
In the opinion of the investigator, the patient is felt not to be appropriate for the study
Patients must have progressive disease based on RECIST Criteria, Version 1.1 while receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease progression must be centrally confirmed. In order to make the assessment, two CT (or MRI) scans are required. The oldest scan must not be older than 3 years from the date of randomization. The most recent scan must not be older than 4 weeks from the date of randomization. Both scans must be obtained while the patient is receiving the same fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable for either scan to be obtained before or during the time a patient receiving a fixed dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to the Octreotide LAR fixed dose after the OctreoScan® has been obtained.
Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.
Patient must be consented to the study prior to salvage assessment
Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the trial
If radiotherapy is required in a given patient, that patient should be withdrawn from the study
Have one or more symptoms that the Investigator believes to be related to the patient's MTC.
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patient must be able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis
Patient has a history of listeriosis or prior ADXS11-001 therapy
Patient has poorly controlled hypertension and on multiple antihypertensives
Extensive (invasive) loco-regional tumor mass and/or metastatic spread, rendering patient inoperable
If a patient has any serious medical problems which may preclude receiving this type of treatment
Patients on Coumadin therapy are eligible for study; there have been some reports of prolonged INR in this patient population and regular screening is recommend in this population, but this should not exclude a patient from participation
Platelets =< 125,000 cells/ul (blood work will be repeated within 2 weeks and if still abnormal, patient will be excluded)
Platelets >= 20,000/mm^3; this requirement may be waived if patient has hematologic relapse of disease or if patient has not yet recovered counts from chemotherapy
DONOR EXCLUSION: New health conditions which would exclude a transplant donor from a second blood donation are limited, but include:\r\n* New onset of an human immunodeficiency virus (HIV) infection\r\n* Other uncontrolled infection which could be transmitted to the patient by blood cells and would place the patient at significant increased risk of severe morbidity or death\r\n* Significant anemia with hemoglobin (Hgb) =< 10 gm/dl, persisting since the time of the original transplant donation\r\n* History of myocardial infarction or stroke since the time of hematopoietic stem cell transplant (HSCT) donation which might increase the risk of blood donation
Patients with acute leukemia or myelodysplastic syndrome or chronic myelomonocytic leukemia must be in a hematologic remission, defined as < 5% blasts present in both blood and marrow to be referred for evaluation; should a patient have > 5% blasts or a donor not be available by the time the patient is ready for enrollment, the patient will be referred back to their primary hematologist-oncologist for treatment; patients with diseases other than acute leukemia including but not limited to Hodgkin’s and Non-Hodgkin’s lymphoma, CLL/SLL, natural killer T-cell lymphoma (NKTCL), peripheral T-cell lymphoma (PTCL), must have stable disease to their most recent regimen received within 8 weeks if chemo/radiotherapy or within 12 weeks after prior autologous stem cell transplantation; should a patient in either of these scenarios have progressive disease or a donor not be available after enrollment, the patient will be referred back to their primary hematologist-oncologist for treatment; if either of these scenarios are not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease under the current study; if under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol
Patient must meet the organ function requirements as stated in the protocol.
Patient declines participation in NANT 2004-05, the NANT Biology Study.
Patient meets the FDA-approved indication for Atezolizumab treatment in NSCLC.
Any co-morbid condition or social situation, which has a high likelihood of causing poor compliance with the study protocol or jeopardizes the patient's safety.
Patient who underwent TCD boost without counts recovery and are considered for another TCD boost will be treated off protocol
Inclusion Criteria:\n\n For patients with solid tumors:\n\n - documented cKit-positive neoplasms\n\n - Patient must have progressive disease as defined by any of the following:\n\n - SCLC: patient has progressed after at least 1 prior therapy\n\n - GIST : patient has relapsed or has refractory disease, and no further approved\n effective therapeutic option exists\n\n - Patients with other cKit-positive solid tumors: patient has progressed after at least\n one prior line of therapy and no further approved effective therapeutic option exists\n\n - Patient has measurable disease as per RECIST v1.1 criteria\n\n For patients with AML:\n\n - documented cKit-positive acute myelogenous leukemia\n\n - Consent to newly obtained bone marrow aspirate\n\n - Patient must have progressive disease defined as relapsed or refractory non-PML AML\n following standard therapy or for whom no effective therapy exists.\n\n - Blast count < 50,000/mm3\n\n Exclusion Criteria:\n\n For patients with solid tumors:\n\n - Patient has central nervous system (CNS) metastatic involvement unless the CNS\n metastases have been previously treated and the patient is clinically stable and on a\n stable dose of corticosteroids for at least 4 weeks prior to enrollment.\n\n - Patient has the presence of other clinically significant hematologic, cardiac,\n respiratory, gastrointestinal, renal, hepatic or neurological conditions.\n\n - Patient has a history of serious allergic reactions, which in the opinion of the\n investigator may pose an increased risk of serious infusion reactions\n\n - Patient has been previously treated with cKit directed antibodies\n\n - Pregnant or nursing women\n\n For patients with AML:\n\n - Patient has received prior allogeneic bone marrow transplant (BMT).\n\n - Patient has the presence of other clinically significant cardiac, respiratory,\n gastrointestinal, renal, hepatic or neurological disease\n\n - Patient has a history of serious allergic reactions, which in the opinion of the\n investigator may pose an increased risk of serious infusion reactions\n\n - Patient has been previously treated with cKit directed antibodies\n\n - Pregnant or nursing women
Patient may not be receiving any other antineoplastic agents
Historical control data will be derived from patient medical records at the Ohio State University Medical Center (OSUMC)
Patient medication lists will be reviewed by a member of the study team for possible interactions with the nelfinavir; a patient may be deemed ineligible for the study if he/she is taking an essential medication that is known to interact with nelfinavir
The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient’s health and survival, than of the MCL, within the subsequent 6 months at the time of consent; investigator discretion is allowed
The patient has an uncontrolled and active infection that would preclude study conduct and assessment
Any condition that, in the clinical judgment of the treating physician, is likely to prevent the patient from complying with any aspect of the protocol or that may put the patient at unacceptable risk.
Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive chemotherapy and/or radiation therapy
Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive chemotherapy and/or radiation therapy
Patient has:
Patient has:
No patient may be entered onto the study without consultation with the principal investigator or his designee
Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
As judged by the investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
FOR PHASE I: If patient is on erlotinib at the time of signed consent, the patient does NOT need to be discontinued prior to initiation of erlotinib and onalespib; other EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and onalespib
FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to receiving treatment erlotinib and onalespib; last dose of erlotinib must be less than 28 days from when patient signs consent
Patient must have a palpable femoral/radial pulse in the affected extremity
Patient has Grade B aGvHD with skin-only involvement.
Patient has had prior treatment with mesenchymal stem cells (MSCs), including remestemcel-L.
Patient shows evidence of encephalopathy as defined by a change in mental status since the onset of aGVHD.
Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed).
Patient has a foreign body which in the opinion of the treating investigator could be difficult to manage in case of infection (e.g. prosthetic hip).
AST and ALT < 10 x ULN AND decreasing at two timepoints if patient is status/post (s/p) biliary stenting
Patient has received 6 cycles of DI-Leu16-IL2 on Protocol AO-101
Patient Re-enrollment: This study permits the re-enrollment of a patient that has discontinued the study as a screen failure (ie, patient has not been dosed/has not been treated). If re-enrolled, the patient must be re-consented.
Inappropriate risk to the patient such as cardiorespiratory compromise such that safe conscious sedation or prone decubitus cannot be obtained
Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures. For example, consider requirement to take mocetinostat with water and recommendation to avoid agents that increase gastric pH
Patient better served by concurrent chemoradiotherapy: the protocol recognizes that institutional standards regarding which patients are best served by operative and nonoperative approaches vary; therefore, consistent with the American College of Chest Physicians (ACCP) guidelines, the protocol recommends multidisciplinary discussion of each patient and enrollment only of patients felt best served by the approach described herein
The tumor must be deemed as being borderline resectable; final computed tomography (CT) confirmation of surgical staging/eligibility will be at the discretion of the pancreatic surgeon of the patient
Patient has no evidence of jaundice at the time of enrollment; if stent is required to alleviate jaundice, it should be metallic; if patient has a previously placed stent and this is plastic, this should be changed to metallic
Inclusion Criteria Include:\n\n - Patient has histologically- or cytologically- confirmed metastatic or advanced-stage\n solid malignant tumor that is refractory to standard therapy and for whom no therapy\n exists that would be curative or might provide significant benefit and therefore for\n whom experimental therapy is a reasonable option.\n\n - Patient experienced progressive disease during or following or was intolerant of their\n most recent treatment regimen.\n\n - Patient is male or female aged ?18 years.\n\n - Patient has an ECOG performance status of 0 (fully active, able to carry out all\n pre-disease activities without restriction) or 1 (unable to perform physically\n strenuous activity but ambulatory and able to carry out work of a light or sedentary\n nature), as assessed on C1D1, before the first dose of TVB 2640.\n\n - Patient has adequate renal function (creatinine ?1.5 times the upper limit of normal\n [ULN]) or a glomerular filtration rate (GFR) of ?50 mL/min.\n\n - Patient has adequate hepatic function,\n\n - Patient has adequate bone marrow function\n\n - Patient has no significant ischemic heart disease or myocardial infarction (MI) within\n 6 months before the first dose of TVB 2640 and currently has adequate cardiac function\n\n For the Monotherapy Expansion Cohorts of the Study ONLY:\n\n - Patient has a specific tumor-type and histology, as designated by the Sponsor based on\n nonclinical and clinical data obtained prior to enrollment in the Expansion Cohort.\n\n - Patient has measurable disease, as determined by the Investigator using RECIST,\n version 1.1 (1).\n\n For the Combination Cohorts ONLY:\n\n - In addition to meeting monotherapy criteria above, the commercially-available\n anticancer agent of interest being investigated in combination with TVB-2640,\n administered according to the dose regimen in the prescribing information, is deemed\n appropriate for the patient's disease and clinical status.\n\n Exclusion Criteria Include:\n\n - Patient is unable to swallow oral medications or has impairment of GI function or GI\n disease that may significantly alter drug absorption\n\n - Patient has uncontrolled or severe intercurrent medical condition (including\n uncontrolled brain metastases).\n\n - Patient underwent major surgery within 4 weeks before the first dose of TVB 2640 or\n received cancer-directed therapy or an investigational drug or device within 4 weeks\n (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is\n shorter) before the first dose of TVB 2640.\n\n - If female, patient is pregnant or breast-feeding.\n\n - Patient has evidence of a serious active infection\n\n - Patient has a history of other malignancy treated with curative intent within the\n previous 5 years with the exception of adequately treated non-melanoma skin cancer or\n carcinoma in situ of the cervix.
Part A only: For patient who has been treated with afatinib: last treatment at reduced dose below the assigned dose level
Patient is contraindicated for endoscopic procedure for any reason
Patient presents with esophagorespiratory fistula
Any other factor identified by the Investigator that would disqualify the prospective patient from participation in the study including but not limited to coagulative disorders and anesthetic risk.
patient was currently benefiting from treatment with single agent oral dovitinib or dovitinib and fulvestrant coadministration as determined by the guidelines of the parent protocol and according to the investigator's clinical judgment.
patient had demonstated compliance
Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present
Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Patient has a GAD-7 mood scale score ? 15.
Males must agree to use condoms during sex to prevent spillage of semen for the duration of the study and for 3 months after the patient leaves the study
Inclusion Criteria:\n\n Patients are eligible if they:\n\n 1. have undergone noncardiac surgery;\n\n 2. are ?45 years of age;\n\n 3. have suffered MINS based upon fulfilling one of the following criteria: A. Elevated\n troponin or CK-MB measurement with one or more of the following defining features i.\n ischemic signs or symptoms (i.e., chest, arm, neck, or jaw discomfort; shortness of\n breath, pulmonary edema); ii. development of pathologic Q waves present in any two\n contiguous leads that are ?30 milliseconds; iii. electrocardiogram (ECG) changes\n indicative of ischemia (i.e., ST segment elevation [?2 mm in leads V1, V2, or V3 OR ?1\n mm in the other leads], ST segment depression [?1 mm], OR symmetric inversion of T\n waves ?1 mm) in at least two contiguous leads; iv. new LBBB; or v. new or presumed new\n cardiac wall motion abnormality on echocardiography or new or presumed new fixed\n defect on radionuclide imaging B. Elevated troponin measurement after surgery with no\n alternative explanation (e.g., pulmonary embolism, sepsis) to myocardial injury; AND\n\n 4. provide written informed consent to participate within 35 days of suffering their\n MINS.\n\n Exclusion Criteria:\n\n Patients meeting any of the following criteria will be excluded:\n\n 1. hypersensitivity or known allergy to dabigatran;\n\n 2. history of intracranial, intraocular, or spinal bleeding;\n\n 3. hemorrhagic disorder or bleeding diathesis;\n\n 4. known hepatic impairment or liver disease expected to have an impact on survival;\n\n 5. condition that requires therapeutic dose anticoagulation (e.g., prosthetic heart\n valve, venous thromboembolism, atrial fibrillation);\n\n 6. currently using or plan to initiate rifampicin, cyclosporine, itraconazole,\n tacrolimus, ketoconazole, or dronedarone;\n\n 7. women who are pregnant, breastfeeding, or of childbearing potential who refuse to use\n a medically acceptable form of contraception throughout the study;\n\n 8. investigator considers the patient unreliable regarding requirement for study\n follow-up or study drug compliance; OR\n\n 9. previously enrolled in the MANAGE Trial.\n\n Also excluded will be patients in whom any of the following criteria persist beyond 35 days\n of their suffering MINS:\n\n 1. the attending surgeon believes it is not safe to initiate therapeutic dose\n anticoagulation therapy;\n\n 2. the attending physician believes ASA, intermittent pneumatic compression, or elastic\n stockings are not sufficient for venous thromboembolism (VTE) prophylaxis and that the\n patient requires a prophylactic-dose anticoagulant;\n\n 3. the patient has an indwelling epidural or spinal catheter that cannot be removed, or\n the first dose of dabigatran will occur within 4 hours of epidural catheter removal;\n OR\n\n 4. estimated glomerular filtration rate (eGFR) <35 ml/min as estimated by calculated\n creatinine clearance.\n\n 5. it is expected that the patient will undergo cardiac catheterization for MINS.\n\n Exclusion Criteria Specific to Patients in the Omeprazole Factorial Component of the Trial:\n\n Patients meeting any of the following criteria:\n\n 1. hypersensitivity or known allergy to omeprazole;\n\n 2. requirement for a proton pump inhibitor, an H2-receptor antagonist, sucralfate,\n atazanavir, clopidogrel, or misoprostol;\n\n 3. esophageal or gastric variceal disease; OR\n\n 4. patient declines participation in the omeprazole arm of MANAGE.
Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
Any significant finding in the patient's medical history or physical examination that, in the opinion of the investigator, would affect patient safety or compliance with the dosing schedule.
Patient declines participation in NANT 04-05. (Neuroblastoma Biology Study)
If a patient has any serious medical problems which may preclude receiving this type of treatment
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements; each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate\r\n* A similar process must be followed for sites outside of Canada as per their respective cooperative group’s procedures
Patient has a QT interval prolongation > 480 ms at screening. If a patient has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon Investigator evaluation (ie, the patient otherwise has no cardiac abnormalities), then the patient may be eligible to participate in the study following discussion with the Medical Monitor.
If any patient develops symptomatic diabetes requiring drug therapy, he must receive such a therapy, which may include metformin; this must be documented, and the patient will not continue on the study
Inclusion Criteria (must all be answered \Yes\):\n\n - Has the patient given written informed consent?\n\n - Is the patient between 18 years old and 80 years old inclusive?\n\n - Has the patient had histologically proven HGG with recurrence or progression following\n initial definitive therapy(s) such as surgery with or without adjuvant radiation\n therapy and/or chemotherapy (confirmed by diagnostic biopsy or contrast-enhanced MRI\n and evaluable by Macdonald criteria)? Note if first recurrence of GBM is documented by\n MRI, an interval of at least 12 weeks after the end of prior radiation therapy is\n required unless there is either: i) histopathologic confirmation of recurrent tumor,\n or ii) new enhancement on MRI outside of the radiotherapy treatment field.\n\n - Does the patient have a single, HGG tumor recurrence/progression that is ? 5 cm in its\n greatest dimension?\n\n - Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate\n for ? 80% resection?\n\n - Has the patient elected not to undergo treatment with the Gliadel® wafer?\n\n - Does the patient have a Karnofsky performance status ? 70?\n\n - Does the patient have an absolute neutrophil count (ANC) ? 1500/mm3?\n\n - Does the patient have an absolute lymphocyte count ? 500/mm3?\n\n - Does the patient have a platelet count ? 100,000/mm3?\n\n - Does the patient have a Hgb ? 10 g/dL?\n\n - Does the patient have a normal PT/PTT? (subnormal PT/PTT acceptable)\n\n - Does the patient have an estimated glomerular filtration rate of at least 50 mL/min\n (inclusive) by the Cockcroft-Gault formula?\n\n - Does the patient have an ALT < 3 times the upper limit of the laboratory reference\n range and total bilirubin < 1.5 mg/dL?\n\n - If the patient is a female of childbearing potential, has she had a negative serum\n pregnancy test within the past 21 days?\n\n - Is the patient willing to use condoms for contraception for 6 months after receiving\n Toca 511 or until there is no evidence of the virus in his/her blood, whichever is\n longer. If the patient is a fertile female, is she willing to use contraception for at\n least 12 months?\n\n - Is the patient willing and able to abide by the protocol?\n\n Exclusion Criteria (must all be answered \No\):\n\n - Has the patient received cytotoxic chemotherapy within the past 3 weeks (6 weeks for\n nitrosoureas) of the planned surgery date?\n\n - Does the patient have, or has the subject had, within the past 4 weeks any infection\n requiring antibiotic, antifungal or antiviral therapy?\n\n - Has the patient had a surgical procedure in the last 28 days or a surgical wound that\n is not healed?\n\n - Does the patient have any bleeding diathesis, or must the subject take any\n anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for\n surgery?\n\n - Does the patient have a history of allergy or intolerance to flucytosine?\n\n - Is the patient HIV positive?\n\n - Does the patient have any gastrointestinal disease that would prevent him or her from\n being able to ingest or absorb flucytosine?\n\n - Has the patient received any investigational treatment within the past 30 days?\n\n - Is the patient breast feeding?\n\n - Has the patient received Avastin® (bevacizumab) for this recurrence/progression, or\n within the past 5 weeks?\n\n - Does the patient have a history of prior malignancy, excluding basal or squamous cell\n carcinoma of the skin, with an expected survival of less than five years?
Fatigue which interferes with the patient's quality of life
The patient's blasts cells show expression of WT1 transcript, detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR).The patient received the following therapy according to the Institution's standard of care.
The patient has other concurrent severe medical prob-lems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
Patients with metastatic renal cell carcinoma referred for the study may not be eligible for the experimental protocol therapy due to reasons such as uncertainty about donor HLA typing or need to control malignant disease, infection, or metabolic abnormality such as hypercalcemia on an emergent basis; should a referred patient present to us in such a scenario, the patient will be referred back to their primary hematologist-oncologist for treatment; however, if referral back to the referring physician is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease or complicating conditions (infection, metabolic problems) under the current study; if it becomes apparent that the patient will not be able to proceed to experimental therapy, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol; it is not necessary to complete the eligibility criteria prior to receiving such standard care; however, prior to initiation of the experimental therapy (starting with the pentostatin-cyclophosphamide [PC] regimen), the patient must meet each of the eligibility criteria
The patient's blasts cells show expression of WT1 tran-script, detected by quantitative RT-PCR.
The patient has other concurrent severe medical prob-lems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
No more than 14 days lapse in gefitinib treatment between the patient completing the preceding gefitinib clinical study and beginning of this study except when agreed by the AstraZeneca physician.
Has any other clinically important abnormalities such that risk to patient of participation outweighs the potential benefit of therapy as determined by the investigator
Other patient eligibility requirements\r\n * Human immunodeficiency virus (HIV) 1 and HIV 2 negative\r\n * Not pregnant or at risk for pregnancy and willing to use acceptable birth control methods\r\n * No uncontrolled drug of alcohol abuse; patients will be screened for drug and alcohol abuse by a pediatric psychologist who is a member of the HSCT team; this information will not be recorded in the patients’ hospital chart\r\n * Signed informed consent by patient or legal guardian in accordance with research ethics board guidelines or institutional review board (IRB)\r\n * Lansky or Karnofsky performance score of 0, 1 or 2\r\n * Suitable haploidentical donor available\r\n * Cryopreserved autologous stem cells (minimum 1 x 10^6 cluster of differentiation [CD]34+ cells/kg) available for infusion for patient with solid tumors; subjects with solid tumors who have not had stem cells collected for clinical purposes prior to enrolling in the study will undergo autologous stem cell harvest following standard clinical procedures before beginning the study conditioning regimen
Patient is either ineligible for or declines radical cystectomy; the investigator must explain that a delay in cystectomy may increase the patient’s chance of disease progression
Patient is considered a poor surgical candidate for removal of a renal mass as determined by pre-operative assessment due to the following factors or various combinations thereof:\r\n* Significant comorbidity precluding ability to deliver anesthesia, without compromised ability to undergo systemic chemotherapy with pazopanib as deemed by the Urologist and Medical Oncologist \r\n* Medically documented contraindication for surgery due to religion or risk of blood transfusion\r\n* Size or location of tumor deemed high risk for surgical intervention by Urologist\r\n* Unacceptable risk for anesthesia, such as history of malignant hyperthermia\r\n* Any one of these factors may or may not constitute unresectability, but for consideration for this trial, the surgical and medical oncologist must agree that the particular constellation of findings for the patient under consideration would likely entail a low probability (< 50%) that the tumor would be resectable (with negative margins) or that the potential morbidity associated with an attempt at surgical resection would not be clinically acceptable\r\n* The numerical thresholds noted above are only a guideline and the clinical judgment of the surgeon and medical oncologist will determine unresectability or if patient refuses surgery or other forms of local therapy; the histopathology for this cohort is limited to clear cell carcinoma of the kidney
Patient must have undergone immediate reconstruction at the time of mastectomy or be planning to undergo reconstruction within 8 months after radiation
Patient must be premenopausal at breast cancer diagnosis, as determined locally and documented in patient record; (Note: it is understood that patients’ menopausal status may be unclear at the time of study enrollment)
Patient must be without clinical evidence of loco-regional and distant disease, as evaluated according to institutional assessment standards and documented in the patient record
The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines
Plan to be on chemotherapy or other allowable treatment for at least 3 months (minimum 70 days) and be willing to come in for study visits\r\n* The plan for treatment should be for at least 3 months at time of study enrollment; the treatment can stop earlier during the study at the discretion of the physician and patient (e.g., due to progression as noted through imaging, toxicity, or patient preference)
PATIENT: Lives in a state where their institutions’ PC clinicians are licensed to practice
PATIENT: They are already receiving PC or hospice services
Patient and partner are married or cohabitating and relationship duration >= 1 year
Patient with a history of a thrombotic event within 12 months of starting nintedanib treatment
Patient has constipation that was not primarily caused by opioids, as determined by the investigator
A treating clinician that feels the patient is inappropriate for the study
Patient participants will have an appointment in the Thoracic Oncology Program at the Brigham and Women’s Hospital
Patient lives with a partner (spouse/significant other – includes homo- and heterosexual couples)
PHASE I: Significant developmental delay per patient, parent, or physician report
Patient receiving antiplatelet agents
Patient has had no clinically significant change in renal status within 3 months prior to screening, according to Investigator's review of clinical patient records.
One of the below criteria must be met based on patient's therapy:
Patient cannot be on the following medications: GABA analogues (such as Neurontin, Lyrica), tricyclic antidepressants (such as amitriptyline or nortriptyline)
A relative or a friend upon whom the patient relies for help and who likely to be present during hospitalizations or clinic appointments, or willing to participate by phone
(Patient participation) Normal cognitive status, defined as a normal state of arousal and an absence of obvious clinical findings of confusion, memory deficits or concentration deficits, as determined by the patient's physician
Patient’s attending medical oncologist would not be surprised if the patient died in the next 12 months
Patient has not completed a Physician Orders for Scope of Treatment (POST) form
Patient is willing and able to consent and travel to the class location for 6 weekly 2-hour sessions
Patient has a family member or close friend eligible and interested in participating in the study
Patient reports a score of > 2 on the Activities and Function item from the Patient Generated Subjective Global Assessment (PG-SGA; the patient-reported version of the Eastern Cooperative Oncology Group score)
PATIENT ONLY: Regularly (self-defined) participation in psychotherapy or a formal cancer support group
Patient on stable analgesic regimen for > 7 days without escalation during study period with rescue or immediate release medication every 3 hours or longer
Does not complete baseline patient-reported outcome (PRO) assessment items required to determine stratification or whether the survivor meets inclusion and exclusion criteria
The patient and/or the patient's legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policies approved by the United States (U.S.) Department of Health and Human Services; informed consent must be signed prior to registration on study
Patient has bradyarrhythmia
Workshop A (2017 - 10 weeks- City of Hope)\r\n* Either one of the following:\r\n* City of Hope (COH) cancer patient (all types and at any time point of their disease) OR\r\n* Caretaker/friend family member of the cancer patient
FAMILY CAREGIVERS: Patient’s spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
CAREGIVERS: Family member or friend of an eligible patient.
PATIENTS: Lacks decision-making capacity, as determined by the patient's oncologist.
Patient receiving active intravenous, intraperitoneal or oral chemotherapy
Patient at University of Michigan Gynecologic Oncology Clinic
The oncologist \would not be surprised if the patient died in the next year\
Patient is self-identified as African-American
Patient is anticipating leaving the area within the next 12 months
DCG: Identifies himself/herself as a DCG for the patient
DCG: Lives > 1 hour travel time away from the patient
Patient reports pain, spasms, or urgency symptoms after stent placement, which are thought to be unrelated to other causes as per the patient or healthcare provider or both (documentation in the medical record is unnecessary)
History of patient reported PONV, chemotherapy-induced nausea and vomiting (CINV) or motion sickness
Any patient who is unable to comprehend and operate the activity tracker at the discretion of the enrolling provider
Participants will be recruited by BMT registered nurse (RN) coordinators and physicians prior to patient admission to the Pediatric BMT Unit; caregiver (age 18 years or older) of any patient eligible to undergo autologous or allogeneic BMT and any patient (age 10 years or older) eligible to undergo autologous or allogeneic BMT will be recruited during the “Pre-Transplant Work-up” stage in the outpatient setting
Patient who will be hospitalized to undergo first-time autologous or allogeneic BMT will be given the opportunity to assent/consent and participate in the study; with his/her permission, the patient will also be provided with their own iPad® BMT Roadmap information system to use
Inability to complete or perform measures of patient-reported outcomes or neurocognitive testing on the computer
Lower extremity neuropathy per patient report attributable to oxaliplatin, docetaxel or paclitaxel (neurotoxic chemotherapeutic agent) as determined by patient history of neurotoxic agent administration and no history of other attributable causes such as diabetic neuropathy
PATIENT:
Necessity of awake procedure requiring intraoperative participation of patient due to the presence of the lesion in eloquent brain areas
Has unstable suicidal ideation as determined by the patient's treating psychiatrist
Patient should describe fatigue as being present for a minimum of four days
Patient who eats yogurt equal or more than once a day in the last 3 days
If patient agrees to participate in the optional patient reported outcomes portion of the study, patient must be English speaking and willing to complete the MD Anderson Symptom Inventory (MDASI) questionnaires
Planning to live with the patient for the duration of RT
Participants will be recruited by BMT register nurse (RN) coordinators and physicians prior to patient admission to the BMT Unit; caregiver of any patient eligible to undergo autologous or allogeneic BMT and any patient eligible to undergo autologous or allogeneic BMT will be recruited during the “Pre-Transplant Work-up” stage in the outpatient setting
Patient-assessed ability to walk unassisted
Able to provide informed consent or, if the oncology physician determines the patient to not have decision-making capacity, a patient-designated health care proxy (per institutional policies) must sign consent by the baseline visit
Coming with the patient at the Seidman Comprehensive Cancer Center at University Hospitals Case Medical Center (UHCMC)
Planned treatment for stages I – III cancer at VICC or at MMC (patient)
Treatment expected to last longer than 12 months since this will make it impossible to deliver the end of therapy survivorship care planning session within the study timelines (patient)
Patient expresses inability or unfamiliarity with using SMS/MMS messaging on their phone and is unwilling to be trained in the use of this technology
Caregivers do not need to reside with the patient
Patient with known tracheobronchial anatomical anomalies
Patient requiring sizes not available in DLT or VDLT
The patient has a cell phone capable of receiving text messages
PATIENT: Be those whose attending medical oncologist would not be surprised if the patient died in the next 12 months
PATIENT: Be willing and able to travel to the class location for 6 weekly 2-hour sessions
PATIENT: Not have completed a Physician Orders for Scope of Treatment (POST) form
CANCER PATIENT GROUP: Caucasian or African-American/Black
NON-CANCER PATIENT GROUP: Caucasian or African-American/Black
NON-CANCER PATIENT GROUP: Sedentary defined as < 60 minutes of recreation or work requiring modest PA/week
A relative or a friend, identified by the patient who either lives with the patient or has in-person contact with him or her at least twice per week
Patient unable or not willing to perform all study related biopsies and blood draws for exploratory endpoints will not be enrolled on study as all study related procedures are mandatory
The patient must be less than 6’ 6” in height
The patient must feel comfortable in the prone position
Patient is allergic to components of the study drug; for arms A and B only, patient has perviously taken ibrutinib
Patient has a Patient Generated Subjective Global Assessment (PG-SGA; the patient-reported version of the Eastern Cooperative Oncology Group score) > 2
Patient does not have working phone service
Patient’s spouse, adult child, sibling, parent, other relative, or significant other (defined by the patient as a partner)
Clear indication for antiplatelet agents (e.g., cardiac stents); a patient receiving aspirin for primary prevention prior to index stroke may be enrolled as long as study investigators believe it would be safe for the patient to stop aspirin if the patient was randomized to the enoxaparin arm
Permission from the attending medical oncologist if the patient is currently on an interventional cancer therapy trial
Neutropenia (absolute neutrophil count < 1.0) (bloodwork is not required if patient did not have recent chemotherapy within last 2 weeks)
Relative or friend of patient participant who will likely accompany the patient to clinic visits
Patient on psychiatric hold
Insomnia present for >= 30 days per patient report
Severe marital maladjustment that prevents a patient from benefiting from the proposed intervention (< 85 on the Locke-Wallace Marital Adjustment Test)
Patient must have adequate kidney function as measured by eGFR greater than or equal to 50 calculated from a standard care serum creatinine performed within 30 days prior to the PN; patient must be able to give written informed consent
Patient has a single functioning kidney
Radiation oncology and medical oncology consults must deem patient suitable for protocol treatment
Patient being treated at St. Jude Children's Research Hospital
Pre-morbid condition that prevents patient from ambulating
Patient participating in another biomedical/oral health interventional research study
Patient deprived of freedom, under supervision or guardianship
Patient being treated at St. Jude Children’s Research Hospital
Patient currently residing in a skilled nursing facility
CAREGIVERS ONLY: Able to attend the last two days of the retreat with patient
Bothersome hot flashes (defined by their occurrence >= 28 times per week [about 4 per day]) and of sufficient severity to make the patient desire therapeutic intervention
Patient with poor bowel preparation
INHALATION: Patient has known respiration problems (i.e., emphysema)
Medical comorbidities making surgery unsafe as determined by the patient's surgeon
PATIENT (AS PER SELF-REPORT)
Patient has taken phenothiazines (prochlorperazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine, etc.) for any indication within the last 48 hours prior to the start of treatment with study drug
Patient elects to undergo active surveillance
Patient has taken finasteride or dutasteride during the prior 6 months
Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services
Patient is enrolled on an investigational nonmyeloablative HCT protocol or a nonmyeloablative treatment plan with postgrafting CSP that does not use acute GVHD as its primary endpoint (protocol 2546 serves as adjunct protocol); OR
Patient is not enrolled on an investigational nonmyeloablative HCT protocol, in which case protocol 2546 serves as an independent primary treatment protocol and the patient must meet the following inclusion and exclusion criteria:
Patients < 12 years of age must be approved by the principal investigator and by a relevant patient review committee, such as the Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC)
Patient has used a probiotic dietary supplement within the previous 30 days of enrollment; (consumption of yogurt products is allowed)
Patient is allergic to the third or fourth generation celphalosporins, carbapenem, or aminoglycosides which are used to empirically treat LBP bacteremia
Patient not already seen by UKanQuit staff as part of the hospital based clinical service
Inclusion Criteria:\n\n Diagnosis and Criteria for Inclusion:\n\n All patients:\n\n To be considered eligible to participate in this study, all of the following requirements\n must be met:\n\n 1. Patient, male or female, is at least 18 years of age.\n\n 2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy\n or for which standard therapy is not likely to provide meaningful benefit, or patient\n has refused standard therapy.\n\n 3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n\n 4. Patient is able to take oral medications.\n\n 5. Female patient, if of childbearing potential, has a negative serum pregnancy test\n within 72 hours prior to taking study drug and agrees to abstain from activities that\n could result in pregnancy from enrollment through 120 days after the last dose of\n study treatment, or be of non-childbearing potential. Non-childbearing potential is\n defined as (by other than medical reasons):\n\n - ?45 years of age and has not had menses for > 1 year.\n\n - Amenorrheic for < 2 years without a hysterectomy Post hysterectomy, bilateral\n oophorectomy, or tubal ligation..\n\n Note: Abstinence is acceptable if this is the established and preferred contraception\n for the patient.\n\n 6. Male patient agrees to use an adequate method of contraception starting with the first\n dose of study treatment through 120 days after the last dose of study treatment..\n\n 7. Patient is able to understand the study procedures and agrees to participate in the\n study by providing written informed consent.\n\n Patients with normal hepatic function (Group 1):\n\n Patients screened for the normal hepatic function group must meet the following additional\n criteria to be eligible for enrollment:\n\n 1. Patient has no history of hepatic impairment.\n\n 2. Patient has liver function test (LFT) results within normal range:\n\n - Total bilirubin ? ULN\n\n - Aspartate aminotransferase (AST) ? ULN.\n\n - INR ?1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR\n is within therapeutic range of intended use of anticoagulants.\n\n 3. Patient has adequate hematologic and renal function as defined below:\n\n - Absolute neutrophil count ?1500/µL\n\n - Platelets ?100,000/µL\n\n - Hemoglobin ?9 g/dL\n\n - Serum creatinine ?1.5 × ULN or a calculated creatinine clearance ?60 mL/min using\n the Cockcroft-Gault equation.\n\n Patients with moderate hepatic impairment (Group 2):\n\n Patients screened for the moderate hepatic impairment group must meet the following\n additional criteria to be eligible for enrollment:\n\n 1. Patient has stable, moderate hepatic impairment, defined as:\n\n - BILI: >1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1\n\n - AST: Any value\n\n - INR less than 1.8 unless the patient is receiving anticoagulant therapy and the\n INR is within therapeutic range of intended use of anticoagulants.\n\n 2. Patient has hematologic and renal function as defined below:\n\n - Absolute neutrophil count ?1000/µL\n\n - Platelets ?75,000/µL\n\n - Hemoglobin ?8 g/dL\n\n - Serum creatinine ?1.5 × ULN or a calculated creatinine clearance ?60 mL/min using\n the Cockcroft-Gault equation.\n\n 3. Patient's hepatic disease is deemed stable by the Investigator\n\n Criteria for Exclusion:\n\n Patients will not be eligible for study entry if any of the following criteria are met:\n\n All patients:\n\n 1. Patient has undergone palliative radiotherapy within 1 week of study drug\n administration, encompassing >20% of the bone marrow.\n\n 2. Patient is starting chemotherapy within 3 weeks of study drug administration.\n\n 3. Patient has a known hypersensitivity to the components of niraparib or excipients\n\n 4. Patients who received colony-stimulating factors within 2 weeks prior to the first\n dose of study treatment are not eligible.\n\n 5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for\n neuropathy, alopecia or fatigue.\n\n 6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases.\n\n 7. Patient has undergone major surgery within 3 weeks of starting the study or patient\n has not recovered from any effects of any major surgery.\n\n 8. Patient is considered a poor medical risk due to a serious, uncontrolled medical\n disorder (other than hepatic impairment) or active, uncontrolled infection.\n\n 9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of\n receiving niraparib.\n\n 10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving\n study treatment or for 3 months after the last dose of study treatment.\n\n 11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid\n leukemia (AML).\n\n NOTE: Exclusion Criteria 12-16 apply patients participating in the PK phase of the\n study.\n\n 12. Patient is currently receiving, or unable to refrain from taking from 4 days prior to\n dosing until the time of the last PK blood draw, any of the following cytochrome (CYP)\n 1A2 substrates: alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, and\n theophylline.\n\n 13. Patient is unable to refrain from any intake of grapefruit or grapefruit juice within\n 4 days of the first administration of niraparib until the final PK sample collection.\n\n 14. Patient is currently receiving, or unable to refrain from taking from 4 days prior to\n dosing until the last PK blood draw, any of the following P-glycoprotein (P-gp)\n inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin,\n conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine,\n itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine,\n ticagrelor and verapamil.\n\n 15. Patient is taking proton pump inhibitors, antacids, or histamine 2 (H2) blockers\n within 48 hours prior to niraparib administration, and/or within 6 hours after\n niraparib administration.\n\n 16. Patient has esophagogastrointestinal disease or resection that is likely to interfere\n with the absorption of niraparib.\n\n Patients with moderate hepatic impairment (Group 2):\n\n Patients screened for the moderate hepatic impairment group who meet any of the following\n additional criteria will be excluded from the study:\n\n 1. Patient has hepatic encephalopathy, severe portal hypertension and/or porto-systemic\n shunt.\n\n 2. Patient has fluctuating or rapidly deteriorating hepatic function as determined by the\n investigator within the screening period.\n\n 3. Patient has acute liver disease caused by drug toxicity or by an infection.\n\n 4. Patient has biliary obstruction or other causes of hepatic impairment not related to\n parenchymal disorder and/or disease of the liver.\n\n 5. Patient has esophageal variceal bleeding within the past 2 months.\n\n 6. Patient is receiving anticoagulant therapy with warfarin or related coumarins.\n\n 7. Patient has a history of hepatic transplant, systemic lupus erythematosus, or hepatic\n coma.
Patient choosing PSDO or RRSO must desire permanent sterilization
Patients with recent/ongoing pneumonia (< 15 days from initial surgical patient evaluation)
HIV-positive patient at Thomas Street Health Center
The patient must be willing to provide blood, urine, stool and saliva samples as required by the study
Patient must be cleared for bevacizumab administration with respect to any recent surgeries, and post-surgical scans must confirm the presence of measurable residual disease
The patient has diagnosed cancer of the cervix, vulva, or endometrium
The patient has an intermediate risk of malignancy (5-65% per the Mayo Model) and is in need of diagnosis for alternative treatment, OR The patient has a high probability of cancer (>65%) and will be referred for surgical evaluation or stereotactic body radiation therapy (SBRT). Note: If the patient refuses surgery or if the surgeon requests a definitive diagnosis prior to surgery the patient will have the option to be included in this study,
Patient capable of making informed decisions regarding his/her treatment
Pregnancy or lactation. Future plans for pregnancy do not exclude patient participation. Patient should not become pregnant within one month of completion of 18F-DA PET scan
As per patient report or as confirmed by the medical record, if the patient is taking anti-depression or anti-anxiety medication, < 2 months on these medications or a change in the prescribed dose in the past 2 months
Patient agrees to participate in the clinical study and to complete all required visits and evaluations. The pediatric population has a different disease profile from the glioma patients we hope to recruit. To reduce heterogeneity in the patient population we will not consider patients younger than 18 for this study.
The patient is found to have unfavorable anatomy to indicate that stereotactic biopsy could not be safely performed.
Patient may be of any race/ethnicity
Patient girth exceeds the bore of the PET/MRI scanner
Patient with metastatic disease (from primaries other than lung) who have suspicious mediastinal or hilar LN that require sampling
Presence of visual impairment to an extent that the patient is unable to complete the computer testing
Inability to adequately oxygenate the patient during the procedure
Acute respiratory failure with hypercapnia (unless the patient is intubated and ventilated)
Patient is being considered for SBRT
PATIENT: Patients with congenital heart defects
Patient must be seen at the St. Louis Children’s Hospital Neurofibromatosis (NF) Clinic
Patient must have histological or cytological confirmed breast cancer and fall into one of the following categories:\r\n* New diagnosis with plans for at least 6 months of neoadjuvant ET or any amount of neoadjuvant ET if surgery is planned as this will be used for response assessment \r\n* Patients with newly diagnosed metastatic breast cancer or patient with known metastatic disease who has progressed while on therapy (no washout period is needed if the patient was treated with aromatase inhibitors [AIs] or chemotherapy, but 2 months washout period is needed if the patient was treated with tamoxifen) who are going to be treated with ET
Any patient with tachycardia defined as heart rate (HR) of 100 or higher at the day of SPECT will not be eligible for this study
Patient to be treated with neoadjuvant chemotherapy or patient to be treated with definitive radiation therapy (RT), sequential chemotherapy (chemo)-RT, or concurrent chemo-RT (minimum dose of 50 Gy in 25 fractions)
The patient has an orbital mass which needs further diagnostic evaluation before treatment or for monitoring
The patient should not participate in this study is any of the following applies to the patient: the patients has a pacemaker, metallic cardiac valve(s), magnetic material such as surgical clips, implanted electronic infusion pumps or any other condition that would interfere with the MRI, the patient has a stent somewhere in the body, the patient has a history of allergic reaction to any metals, contrast agents, x-ray dyes, the patient has claustrophobia
The patient and/or the patient’s legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained, in accordance with institutional policies approved by the US Department of Health and Human Service
Any patient with permanent braces, permanent retainers or nonferrous implant that, in the judgement of the principal investigator, would interfere with obtaining spectroscopy in the area of the tumor
Patient is ? 18 years old at the time of the drug administration (Patient may be male or female of any race / ethnicity.)
Patient declines procedures that might be necessary for optimal primary cytoreduction (i.e. colostomy or splenectomy)
The protocol nurse will check with the patient that there is no history of (h/o) kidney disease
Patient is participating in other research protocols at the time of the NaF/FDG PETMRI scan
Patient with sinonasal carcinoma
The clinician/patient has made the decision as to whether the patient will proceed to wide local excision or mastectomy or patient has been diagnosed with invasive disease\r\n* NOTE: if surgical decision is delayed greater than 10 weeks after the MRI or patient is diagnosed with invasive disease, the patient should register to Step 2, arm B, and proceed to follow-up to capture all relevant data
The Oncotype DX Patient Report of the DCIS Score from the Oncotype DX Breast Cancer Assay performed by Genomic Health on the excision tissue have been uploaded by the site into the Rave electronic case report forms (eCRF)\r\n* NOTE: Prior to registration to Step 3, the institution must upload a redacted copy of the first page of the “Oncotype DX Patient Report” to the ‘DCIS Score’ eCRF in Rave; after submission of the Oncotype DX Patient Report, the institution may proceed to register the patient to Step 3
Patient may be part of other clinical trials (as long as no other local treatments beyond GK such as WBRT or other local therapy are indicated to the brain) or imaging studies
Patient must not require sedation for imaging purposes
Surgeon and medical oncologist agree one week window trial is appropriate/safe for the patient and that surgery appointment/initiation of therapeutic systemic therapy can accommodate treatment schedule as outlined in the study schema
Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements
The patient has hepatic dysfunction confirmed by bilirubin > 2 x normal (based on reference values from the laboratory used by the patient)
the investigational PET or SPECT tracer administration was well tolerated by the patient.
Investigator precludes participation for scientific reasons, for reasons of compliance (e.g., concurrent disease which could compromise the subject's study completion), or for reasons of the patient's safety
Female or male adult patient (patient having reached legal majority age)
Patient with national health insurance (according to local regulatory requirements)
Patient presenting with any condition which, based on the investigator's clinical judgment, would prevent the patient from completing all trial assessments and visits
The principal investigator determines that the patient is acting in ways that would lessen their chances of completing the study
Patient must have selected mastectomy for surgical option of treatment
Patient has two separate same histology lung tumors (where the question of two separate primaries or metastatic disease makes definitive clinical staging inaccurate)
Patient gives informed or surrogate consent
Patient will have vocal fold leukoplakia or other abnormal epithelial changes
As judged by the investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
* Patient volunteers for the DW- and DCE-MRI sequence parameter optimization portion of the study are exempt from these criteria
* Patient volunteers for the DW- and DCE-MRI sequence parameter optimization portion are exempt from these criteria
In the opinion of the investigator, the patient is felt not to be appropriate for the study
As judged by the investigator, the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements
A member of the patient’s surgical team must indicate equipoise for the benefit of the surgical treatment for MBO; the surgeon must respond “Yes” to each of the following questions and sign the S1316 Surgical Equipoise Documentation form for the patient to be eligible:\r\n* Is surgery for treatment of malignant bowel obstruction (MBO) being considered for this patient?\r\n* Do you have equipoise? if the treating team finds that an operation is required (e.g., for acute abdomen), or they would not offer the patient an operation (e.g., patient is too weak to tolerate surgery), then there is no equipoise
PATIENT: MSK patients
PATIENT: Willingness to be audio-recorded as per self-report
CAREGIVERS: A relative or a friend upon whom the patient relies for help and who will be likely to be present during hospitalization, or willing to participate by phone
Patient on the gynecologic oncology service
A referring physicians estimate of patient life expectancy must be between 1-12 months
Any patient who has lost MMR and is eligible for re-starting dasatinib therapy must not have developed a condition that precludes dasatinib use.
The patient is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids.
The patient is receiving colony stimulating factors (CSFs) that cannot be held during the monitoring period for dose-limiting toxicities (DLT).
Inclusion criteria:\n\n 1)15-29 year olds receiving treatment for any type of cancer, either primary or\n recurrent/relapsed disease.\n\n 2) Patient has completed at least one month of therapy\n\n 3)Patient is expected to remain on therapy for 3 month duration of study\n\n 4) Patient has an iPhone, iPad, or iTouch running iOS 4.0 or later\n\n 5) Patient is willing to use a smart-phone medication reminder application-\n\n Exclusion Criteria:\n\n 1)Patients who are unable to speak/read/write English as required for use of smart-phone\n medication reminder application and completion of study measures.
Inclusion criteria:\n\n 1)15-29 year olds receiving treatment for any type of cancer, either primary or\n recurrent/relapsed disease.\n\n 2) Patient has completed at least one month of therapy\n\n 3)Patient is expected to remain on therapy for 3 month duration of study\n\n 4) Patient has an iPhone, iPad, or iTouch running iOS 4.0 or later\n\n 5) Patient is willing to use a smart-phone medication reminder application-\n\n Exclusion Criteria:\n\n 1)Patients who are unable to speak/read/write English as required for use of smart-phone\n medication reminder application and completion of study measures.
Before the patient is enrolled, the consent form, including any addenda, must be signed and dated by the patient and the person who explains the study to that patient
Any additional medical condition, serious concurrent illness, or other extenuating circumstance that, in the opinion of the investigator may significantly interfere with study compliance.
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance
Any additional medical condition, serious intercurrent illness or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study performance or interpretation
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance
Does the subject have any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance
Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance
Presence of any additional medical condition such as inter-current illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance
Any additional medical condition, serious concurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance
Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Logistical or psychological hindrance to participation in clinical research
Logistical or psychological hindrance to participation in clinical research
Chronic or acute renal or hepatic disorder or any other condition, medical or psychological that, in the opinion of the investigator, could jeopardize the subject’s safe participation
Physical or psychological condition which would impair study participation; or
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc) that, in the judgment of the investigator, may affect the patient’s ability to sign the informed consent and comply with study procedures
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
Any other co-existing medical or psychological condition(s) that will preclude participation in the study or compromise ability to give informed consent and/or comply with study procedures.
Patients with psychological or geographic conditions that prevent adequate follow-up or compliance with the study protocol.
Any medical or psychological condition that, in the opinion of the investigator, might interfere with the subject’s participation in the trial, poses any additional risk for the subject, or confounds the assessment of the subject
Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded
DONOR: No psychological traits or psychological or medical conditions which make them unlikely to tolerate the procedure
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
Any medical or psychological condition or situation deemed by the principal investigator (PI) to put the patient at increased risk of complications or noncompliance
Patients with any serious/poorly controlled medical or psychological conditions that would be exacerbated by treatment, would complicate protocol compliance
History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the investigator, would impair study compliance
Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded
DONOR: Serious medical or psychological illness
Psychological condition that renders the patient unable to understand the informed consent
Psychological or social reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
Psychological or social reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
Patients with psychological or geographic conditions that prevent adequate follow- up or compliance with the study protocol.
Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor
Any condition (psychological, physical or use/abuse of substances) which, in the opinion of the principal investigator (PI) or a sub-investigator (sub-I), would possibly endanger the subject during their participation in the study, or allow for non-compliance with the investigational drug and treatment under study
Must not have concomitant medical, psychological or social circumstances which would interfere with compliance with the protocol treatment and follow-up
Patients with concurrent medical, psychological or social conditions of such severity that the investigator deems it unwise to enter the patient on protocol
Unrelated Donor: Serious medical or psychological illness
DONOR: Serious medical or psychological illness
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
The participant has any condition (for example, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggests that the participant is, in the investigator's opinion, not an appropriate candidate for the study.
Medical, social, or psychological factors that would prevent the patient from receiving or cooperating with the full course of therapy
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor
Social or psychological conditions that the investigator judges may compromise study compliance
Medical or psychological impediment to probable compliance with the protocol
DONOR: Donors must not have psychological traits or psychological or medical conditions which make them unlikely to tolerate the procedure
Uncontrolled concurrent significant medical or psychological co-morbidity
Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient’s risk, interfere with the patient’s participation in the study, or hinder evaluation of study results
Patients must not have active uncontrolled infections, other medical or psychological/social conditions that might increase the likelihood of patient adverse effects or poor outcomes
Medical, psychological or surgical condition which the investigator feels might compromise study participation
Physical or psychological condition which would impair study participation; or
Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc) that, in the judgment of the investigator, may affect the patient's ability to sign the informed consent and undergo study procedures.
Has medical, social, or psychological factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures
Subjects with a medical or psychological impediment to probable compliance with the protocol
Any significant psychological, medical, or surgical condition thought to compromise the participant, the study, or prevent informed consent
Medical, psychological or surgical condition which the investigator feels might compromise study participation
No medical, psychological or surgical condition which the investigator feels might compromise study participation
Patients with severe psychological or medical illness
History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance
Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
Unstable or severe uncontrolled medical, psychological, or social condition
Other medical or psychological conditions that would make participation unsafe or inhibit our ability to test our primary hypothesis, e.g. Parkinson’s disease, severe dementia
Major psychological condition that would preclude completion of the intervention
Known history of a neurological and/or psychological disorder that in the physician’s opinion may interfere with the patient’s ability to cooperate with study procedures
Presence of psychiatric or psychological symptoms which in the judgment of the principal or associate investigators would compromise the donor’s ability to engage in the intervention or is likely to interfere with the study procedures or results
History of a neurological or psychological disorder that may interfere with the patient’s ability to cooperate with study procedures
Mental incapacitation or significant emotional or psychological disorder that, in the opinion of the investigators, precludes study entry
Has a condition or psychological difficulties that affects day-to-day activities
Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject’s ability to comply with the protocol requirements
Any concurrent condition, including psychological and social situations, which, in the opinion of the investigator, would adversely impact the subject or the interpretation of the study data.
