• Age ≥ 18 years.
• Histological confirmation of p16+ OPSCC or HPV(+) OPSCC.
• Plan for gross total surgical resection via trans oral surgery with curative intent and at least unilateral neck dissection OR chemoradiotherapy.
• Absence of distant metastases on standard diagnostic work-up ≤ 16 weeks prior to registration. (Chest CT or PET/CT).
• ECOG Performance Status (PS) ≤ 1 (Appendix I).
• Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willing to provide tissue and blood samples for correlative research purposes, including anonymous shipment of samples to for NavDx Testing.

Exclusion Criteria

• Any of the following:
  • Pregnant women;
  • Nursing women;
• Men or women of childbearing potential who are unwilling to employ adequate contraception.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV+.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy ≤ 5 years prior to registration.
• EXCEPTIONS:
  • Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or prostate or localized endometrioid endometrial cancer.
  • NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer.
• Prior history of radiation therapy to the affected site.
• Prior systemic chemotherapy in the last 5 years.
• Contraindication to radiation therapy as determined by the treating team.
• History of allergic reaction to docetaxel.
• Receiving any medications or substances which in the opinion of the investigators would interfere with treatment. Examples could include strong inhibitors of CYP3A4 at oncologist discretion.
• Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy.
• cT4 primary tumor:
  • NOTE: Patients with no intermediate risk factors after surgery, low risk patients, as defined by T1, T2, tumors with lymph node less than 3cm, no intermediate or high risk factors such as LVSI, ENE, PNI, positive 22 margin, will go off study and be observed per current clinical standard of care. Patients found to have HPV non 16 type, or HPV detectability in blood less than < 20 TTMV will not be candidates for de-escalation in Groups 1 and 2 and will be treated in Group 3. They will receive 60 Gy +/- cisplatin or acceptable alternate regimen when drug shortages of cisplatin exist, see section 7. If treated primarily with chemoRT (Group 4), these patients will not be candidates for de-escalation if TTMV is < 50 TTMV but can remain on study receiving 70 Gy with all corresponding correlative studies applying. Patients with unknown (radiologic/clinically occult) primaries but p16+ or HPV+ neck adenopathy can be registered to go on study. Should after primary resection, no primary tumor be identified, the patient will go off study and be treated per institutional standard of care.
  • All treatment primarily, including surgery and chemotherapy will be performed at the enrolling institution.

Eligibility last updated 7/26/23. Questions regarding updates should be directed to the study team contact.

• Phase 1 dose escalation only: solid tumor malignancies with homozygous deletion of the CDKN2A gene may be eligible for enrollment if the CDKN2A assay is approved by the Sponsor. Note: solid tumor malignancies with homozygous deletion of the CDKN2A gene and known wild-type MTAP gene are not eligible.

- Unresectable or metastatic disease.

- Patients must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment.

1. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease.

2. Phase 1b and Phase 2 cohorts, RECIST 1.1 measurable disease.

- Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.

- Age ≥ 18 years.

- Recovery from the adverse effects of prior therapy at the time of enrollment to baseline or ≤ Grade 1 (excluding alopecia, peripheral neuropathy, and parameters superseded by other eligibility criteria [eg, hematology parameters]). Note: Patients with prior endocrine adverse effects are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Adequate organ function.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/10/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Childre:

• Ages 3-7.
• Outpatients.
• Any gender, race, or ethnicity.
• Able to provide developmentally appropriate informed assent, and legal guardians able to provide informed consent.
• EBP Severity rated above the clinically significant range (≥120; T-score ≥ 60) (Eyberg Child Behavior Inventory- ECBI; Eyberg & Pincus, 1999).
• Families approached for participation will be asked to commit to complete the treatment:
• At least one primary caregiver and the identified child will have to be able to speak and understand English;
• Must have the ability, technology, and internet access for remote therapy/research visits.   

Inclusion Criteria
•Adults:

• Agree to wear Garmin watch.
• Ages 18-99.
• Any gender, race, ethnicity.
• Able to provide informed consent.
• Able to speak and understand English.
• Has the ability, technology, and internet access for remote therapy/research visits.

Exclusion Criteria
•Children: 

• Formal diagnosis of Severe Intellectual disability, Autistic Spectrum Disorder Level 3, or a psychotic disorder for the child.
• Parents not consenting to the study.
• Parents or child is not able to adhere to the study protocol.
• A Child who is reasonable expected to be unable to tolerate wearing the Garmin device for at least 70% of the time during the day and night 70% of the days during the treatment (12 weeks). This is based on the principal investigator’s discretion.
• Unable to speak and understand English.
• Refusal or withdrawal of consent, inability, or unwillingness to adhere to study procedures.
• Children in foster care.
• Does not have the ability, technology, and/or internet access for remote therapy/research visits.
• Need for more intensive behavioral treatments such as ER visit for behavioral dyscontrol or hospitalization will not be exclusionary or exit criteria.

Exclusion Criteria
•Adults:

• Unable to speak and understand English. 
• Refusal or withdrawal of consent, inability, or unwillingness to adhere to study procedures.

Eligibility last updated  10/19/22. Questions regarding updates should be directed to the study team contact.

• ≥ 18 years of age.
• Radiographic findings consistent with a lesion with high pre-procedure probability of malignancy as determined by the investigator to be NSCLC 8th Ed. stage IIB- IIIA cancer or biopsy-confirmed NSCLC 8th Ed. stage IIB-IIIA and lesion size ≤ 5 cm in greatest dimension.
• Lesion is targetable for biopsy and PEF delivery per investigator opinion.
• Patient deemed able to complete neoadjuvant therapy according to their EGFR/ALK mutation status and specific histology (if clinically appropriate) and per the manufacturer’s systemic therapy labeling.
• Patient has been deemed a potential candidate for definitive lung tissue resection by a qualified study investigator.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Patient is able to adhere to protocol requirements 8. Patient is able to tolerate general anesthesia.
• Patient is cleared to undergo paralytic anesthesia.
• Patient has provided informed consent.

• Presence of advanced, inoperable, or metastatic disease.
• Radiographically suspicious findings for stage IIIA patients indicating a single mediastinal lymph node > 3 cm or multiple mediastinal lymph nodes and, therefore, potentially inoperable.
• Patient has recurrent NSCLC or has previously been treated for NSCLC.
• Patient has received chemotherapy or any other cancer therapy in 2 years prior to PEF ablation.
• Prior treatment with any drug that targets T cell co-regulatory pathways (such as checkpoint inhibitors) in 2 years prior to PEF ablation.
• Patient has implanted lung devices or electronic devices.
• Patient has a serious medical condition that, in the investigator’s opinion, could compromise patient safety or confound the interpretation of the patient’s response.
• Patient requires or is likely to require a pneumonectomy.
• Patient with active, known, or suspected autoimmune disease
  • Patient with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll;
  • Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Patient has received systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immune-modifying or immunosuppressive medications within 30 days prior to study enrollment. Inhaled or topical steroids, and adrenal replacement doses ≤ 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
• Patient has any history of primary immunodeficiency including known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
• Patient has any history of organ transplant that requires use of immunosuppressives.
• Patient has clinical signs or symptoms of active tuberculosis infection.
• Patient has history of (non-infectious) pneumonitis that required steroids or current pneumonitis/interstitial lung disease.
• Patient with ≥ Grade 2 peripheral neuropathy.
• Patient has received any vaccine against infectious diseases (e.g., influenza, COVID-19, varicella, etc.) within 30 days of PEF procedure.
• Patient has documented evidence of acute hepatitis or has an active or uncontrolled infection.
• Patient has undergone major surgery within 30 days prior to study enrollment or has planned for other major surgery to be performed while enrolled in the clinical trial.
• Patient is unable or unwilling to complete all required screening and/or follow-up assessments.
• Patient is currently enrolled in another interventional clinical trial or is receiving treatment with an investigational medication or medical device that conflicts with the study protocol.
• Patient is pregnant or nursing.
• Patient for whom the investigator considers that the PEF ablation is not in the patient’s best interest.
• Patient has active alcohol or drug addiction or any other condition that, in the investigator’s opinion, would interfere with their ability to comply with the study requirements or jeopardize the safety of the patient or compliance with the protocol.
• Patient is involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

Eligibility last updated 9/6/22. Questions regarding updates should be directed to the study team contact.

• 18 years or older.
• Generally healthy adult (At the discretion of the PI).
• Visitor accompanying a current mayo clinic patient to an appointment.

• Patient and the patient’s visitor cannot be being seen in the dermatology department.
• Known diagnosis of Hidradenitis Suppurativa.

Eligibility last updated 9/13/22. Questions regarding updates should be directed to the study team contact.

• ≥ 18 years of age. 
• Patients with known genetic predisposition to pheochromocytomas and paragangliomas (PPGL) development.
• Patients with history of (PPGL).

• < 18 years of age. 

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/2/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 2/1/23. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 6/6/23. Questions regarding updates should be directed to the study team contact.

• Adult patients, ≥ 18 years old.
• Treated at Mayo Clinic from 2011 to 2019 with pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).
• Alive more than 3 years from the procedure.

• Children < 18 years of age.
• Patients who have undergone pancreatoduodenectomy (PD) for other pathology.

Eligibility last updated 4/26/22. Questions regarding updates should be directed to the study team contact.

- Study participant has positive TB test at the Screening Visit unless it is determined by a TB specialist that the positive result is related to an adequately treated latent TB infection).

Participant meets any of the following TB exclusion criteria:

• Known active TB disease;
• History of active TB involving any organ system unless adequately treated according to World Health Organization (WHO)/Centers for Disease Control and Prevention (CDC) therapeutic guidance and proven to be fully recovered upon consult with an appropriate specialist;
• Latent TB infection (LTBI) (unless appropriate treatment is initiated at least 4 weeks prior to IMP dosing and will be continued to completion). Tuberculosis preventive therapy should be in accordance with applicable clinical guidelines and appropriate specialist judgment.

- High risk of exposure to TB infection, as assessed by the investigator

- Current pulmonary nontuberculous mycobacterial (NTM) infection or history of pulmonary NTM infection unless proven to be fully recovered. For further information relating to definitions of known active TB, past history of TB, LTBI, high risk of acquiring TB infection and NTM infection, see Appendix 12, Section 10.12.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/7/23. Questions regarding updates should be directed to the study team contact.

Two cohorts of patients are planned to be enrolled in the study:

• “New user”: patients starting osilodrostat at study entry;
• “Prior user”: patients that have started osilodrostat any time prior to study entry.

InclusIon Criteria:

• Written informed consent obtained prior to registration of any patient data.
• Male or female patients, aged 18 years or older
• Diagnosed with endogenous Cushing's Syndrome (CS).
• Treated with osilodrostat. Treatment with osilodrostat can either be initiated at the first visit of the study or can have been initiated before screening.

• Patients with exogenous CS.
• Patients with Pseudo CS.
• Patients participating in an interventional clinical trial with an investigational drug.

Eligibility last updated 5/9/22. Questions regarding updates should be directed to the study team contact.

• Provide written informed consent.
• Male or female ages 18 or older.
• Evidence of cancer of the colon or rectum that is metastatic to the liver.
  • NOTE:  patients may enroll prior to receiving clinical biopsy results. If they are not confirmed to have adenocarcinoma of the colon or rectum that is metastatic to the liver, they will not be evaluable.
• Treating physician planning to treat CRC liver metastasis with a standard of care therapy.
• Previous adjuvant or neoadjuvant therapies allowed.
• Biopsy may be obtained prior to starting the 2nd cycle of a new standard of care therapy.
• Measurable disease as measured by RECIST 1.1 criteria.
• Life expectancy of ≥ 12 weeks.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2. 
• Adequate coagulation function as evidenced by:
  • Absolute neutrophil count ≥ 1.0 x 10^9/L;
  • Platelets ≥ 50 x 10^9/L;
  • Hemoglobin ≥ 8 g/dL (transfusions are permitted to achieve baseline hemoglobin level);
• ALT/AST (alanine aminotransferase (ALT) / aspartate aminotransferase (AST)) < 2.5 x upper limit of normal (ULN); or
• < 5 x ULN in the presence of liver metastases;
• Total bilirubin < 1.5 x ULN (if total bilirubin ≥ 1.5 x ULN then the subject may participate if the direct bilirubin is ≤ 1.5 x ULN);
• Creatinine clearance > 30 mL/min measured or calculated by Cockcroft-Gault equation or the estimated glomerular filtration rate (GFR) > 30 mL/min/1.73 m^2 using the MDRD;
• INR < 1.5.

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
• Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of start of therapy, New York Heart Association Class II, III or IV congestive heart failure, and arrhythmia requiring therapy.
• Presence of significant concurrent, uncontrolled medical condition including but not limited to renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, active infection, non-healing wound, or psychiatric disease that excludes them from receiving chemotherapy.
• Pregnant or actively breastfeeding women (Pregnant or breastfeeding women are not candidates for chemotherapy).

Eligibility last updated 7/20/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 5/2/23. Questions regarding updates should be directed to the study team contact.

• Patients ≥ 18 years of age being tested for COVID 19 or Influenza.

• Patients < 18 years of age.

Eligibility last updated 10/27/22. Questions regarding updates should be directed to the study team contact.

• A 15-minute daily stretching program will be implemented for 1 year.
• Personnel working in the departments of Cardiology and Radiology at Mayo Rochester, Mayo Scottsdale, and Mayo Jacksonville and Mayo Clinic Health System.
• Willing to complete standardized questionnaires (DASH, ODI) to assess work-related pain at baseline and at 1 year.
• Employees who respond to questionnaires at baseline and 1 year but don’t participate in the stretching exercises will be controls for the study.
• Willing and able to provide written, informed consent.

• Pregnancy.
• Inability to participate in the stretching exercises for any reason.
• Preexisting musculoskeletal problems that has required employees to seek active medical or orthopedic treatment.

• A 15-minute daily stretching program will be implemented for 1 year.
• Personnel working in the departments of Cardiology and Radiology at Mayo Rochester, Mayo Scottsdale, and Mayo Jacksonville and Mayo Clinic Health System.
• Willing to complete standardized questionnaires (DASH, ODI) to assess work-related pain at baseline and at 1 year.
• Employees who respond to questionnaires at baseline and 1 year but don’t participate in the stretching exercises will be controls for the study.
• Willing and able to provide written, informed consent.

• Pregnancy.
• Inability to participate in the stretching exercises for any reason.
• Preexisting musculoskeletal problems that has required employees to seek active medical or orthopedic treatment.

• Participant must be aged 6 to 17 years, inclusive, at Screening (Visit 1).  
• Participants who have been diagnosed with HES for at least 6 months prior to enrolment (Visit 2).
• A history of 2 or more HES flares within the past 12 months prior to Screening (Visit  1).  
• Participants must have blood eosinophil count ≥ 1000 cells per microliter (/mcL) present at Screening.
• Participants must be on a stable dose of HES therapy for the 4 weeks prior to the  first dose of mepolizumab (Visit 2).
• Male and/or female.
• Signed written informed consent.

• Life-threatening HES or life-threatening HES co-morbidities.
• Other concurrent medical conditions that may affect the participant's safety.
• Eosinophilia of unknown significance.
• Fusion tyrosine kinase gene translocation [FIP1L1.
• Platelet-derived Growth Factor  Receptor (PDGFRα) (F/P)] positivity.
• Clinical diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA).
• Participants with chronic or ongoing active infections requiring systemic treatment, as well as participants who have experienced clinically significant infections due to viruses, bacteria, and fungi within 4 weeks prior to enrolment (Visit 2).
• Participants with a pre-existing parasitic infestation within 6 months prior to  enrolment (Visit 2).
• Participants with a known immunodeficiency (e.g., Human immunodeficiency virus [HIV]),  other than that explained by the use of OCS or other therapy taken for HES
• Participants with documented history of any clinically significant cardiac damage  prior to Screening (Visit 1) that, in the opinion of the investigator, would impact the participant's participation during the study.
• Participants with a history of or current lymphoma.
• Participants with current  malignancy or previous history of cancer in remission for less than 12 months prior to  Screening (Visit 1).
• Participants who are not responsive to OCS based on clinical response or blood  eosinophil counts.  
• Participants who have previously received mepolizumab in the 4 months prior to  enrolment (Visit 2).
• Participants receiving non-oral systemic corticosteroids in the 4-week period prior to  enrolment (Visit 2).  
• Participants who have received any other monoclonal antibodies within 30 days or 5 half-lives, whichever is longer, of enrolment (Visit 2).
• Participants who have received treatment with an investigational agent (biologic or  non-biologic) within the past 30 days or 5 drug half-lives, whichever is longer, prior to enrolment (Visit 2).  
• Use of candidate Coronavirus disease 2019 (COVID-19) vaccines that have not received  limited, accelerated, or full authorization/approval, and are only in use as part of a  clinical trial.  
• Participants who are currently participating in any other interventional clinical study.
• Participants with any history of hypersensitivity to any monoclonal antibody (including mepolizumab).
• Evidence of clinically significant abnormality in the hematological, biochemical, or urinalysis screen from the sample collected at Screening (Visit 1), that could put the participant's safety at risk by participating in the study, as judged by the  investigator.

• Adult (18-90), male/female/other.
• Self-reported racial/ ethnic minority.
• Internet access via mobile device and/or computer/tablet.
• Able to read and write in English or Spanish.

• Legal inability or restricted legal ability. Medical or psychological conditions not allowing proper study completion or informed consent signature.
• Under the age of 18 years old.
• Identified as non-underrepresented racial/ethnic minority or medically underserved minority.
• Unable to read and write in English or Spanish.

Eligibility last updated 11/8/21. Questions regarding updates should be directed to the study team contact.

• Participant must be ≥ 18 years of age, at the time of signing the informed consent.
• Participants who are ≥ 40 kg at Screening Visit 1.
• Participants who have a documented diagnosis of HES prior to Visit 2. HES diagnosis is based on:
  • blood eosinophilia of > 1500 eosinophils/µL on at least 2 occasions at ≥ 1-month interval, without a discernible non-haematological secondary cause; and
  • signs or symptoms of organ involvement and/or dysfunction that can be directly related to eosinophilia.
• Flare history: A history of 2 or more HES flares within the past 12 months prior to Visit 1. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an addition or escalation in OCS or cytotoxic/immunosuppressive therapy. At least one HES flare within the past 12 months must not be related to a decrease in HES therapy during the 4 weeks prior to the flare.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
  • Is a woman of non-childbearing potential (WONCBP); OR
  • Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, from at least 14 days prior to the first dose of study intervention until at least 30 weeks after the last administered dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (e.g., non-compliance, recently initiated) in relationship to the first dose of study intervention;
  • A WOCBP must have a negative highly sensitive serum pregnancy test at Screening Visit 1 and a negative highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention;
  • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies;
  • The Investigator should evaluate the potential for contraceptive method failure (e.g., non-compliance, recently initiated in relationship to the first dose of study intervention;
  • The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

• HES disease manifestations which in the opinion of the Investigator may put the participant at unacceptable risk from study participation or confound interpretation of efficacy or safety data. Specific consideration should be given to the participant’s ability to comply with protocol requirements, including the list of prohibited therapies; exclusion criteria no. 14
  •16.
• Participants with chronic or ongoing active infections requiring systemic treatment.
• Participants with a pre-existing parasitic infestation within 6 months prior to Visit 1.
• Participants with a known immunodeficiency (e.g., Human Immunodeficiency Virus [HIV]), other than that explained by the use of OCS or other therapy taken for HES.
• Participants with a history of or current lymphoma.
• Participants with current malignancy or previous history of cancer in remission for less than 5 years prior to Visit 1. Participants that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded.
• Participants with a haematologic malignancy with hypereosinophilia in which HES is not the primary diagnosis; e.g., chronic myeloid leukaemia, myelodysplastic syndrome, chronic eosinophilic leukaemia-not otherwise specified.
• Cirrhosis or current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice.
  • NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) are acceptable if participant otherwise meets entry criteria.
• Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
• Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at Screening will be evaluated and current vasculitis must be excluded prior to randomization.
• Eosinophilia of unknown significance: Hypereosinophila with no clinical symptoms and/or proof of organ dysfunction.
• Clinical diagnosis of EGPA.
• Participants that, according to the Investigator's medical judgment, are likely to have active COVID-19 infection should be excluded.
• Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant must remain symptom-free.
• Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, cardiac or any other system abnormalities that are not associated with HES and are uncontrolled with standard treatment.
• Participants with an allergy/ intolerance to a monoclonal antibody or biologic, or any of the excipients of the investigational product.
• Monoclonal antibodies (mAbs) targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy.
• Participants who have received mAb within 30 days or 5 half-lives, whichever is longer, prior to Visit 1. If a participant has been treated with and responsive to biologics for HES, the participant should not stop the treatment for study eligibility purpose.
• Non-oral systemic corticosteroids: Participants who have received intravenous, intramuscular, or subcutaneous corticosteroids within 4-weeks prior to Visit 2.
• Participants who have received treatment with an investigational agent within 30 days or 5 drug half-lives whichever is longer, prior to Visit 1. The term “investigational” applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products.
• Participants who are currently participating in any other interventional clinical study.
  • Note: Any COVID-19 vaccine approved by local government is permitted. Experimental COVID-19 vaccines are not permitted.
• Participants who test positive for the FIP1L1-PDGFRα fusion gene. Blood sampling is required for all participants at Screening (Visit 1) for this test unless the documented result is available.
• ECG Assessment: QTcF ≥ 450 msec or QTcF ≥ 480 msec for participants with Bundle Branch Block at Screening Visit 1.
• Participants who are not responsive to OCS based on clinical response or blood eosinophil counts in the opinion of the Investigator.
• A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
• Participants who are pregnant or breastfeeding.
• Participants must not be randomized if they plan to become pregnant during the time of study participation.
• Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.

• Neurogenic bladder diagnosis.
• ≥ 18 years old.
• Non-neurogenic bladder patients undergoing key surgical procedures (urinary diversion, bladder augmentation, creation of catheterizable channel, urethral reconstruction, ureteric reconstruction).

•  < 18 years old.
•  No Neurogenic bladder diagnosis or non-neurogenic bladder patients not undergoing key surgical procedures (urinary diversion, bladder augmentation, creation of a catheterizabel channel, urethral reconstruction, ureteric reconstruction).

Eligibility last updated 4/29/22. Questions regarding updates should be directed to the study team contact.

• Patients with Pulmonary Arterial Hypertension due to Interstitial Lung Disease (ILD-PAH) being considered for inhaled treprostinil.
• Resting right heart catheterization wi.mean pulmonary artery pressure > 20 mmHg and PVR > 3 Wood units.
• Healthy volunteers
  will have no known lung disease, heart failure, muscular disease or pulmonary hypertension, no bleeding abnormalities, and have the ability to exercise.

• Inability to exercise.
• Females who are pregnant.

Eligibility last updated 4/20/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

- Clinical diagnosis of focal epilepsy.

- Estimated to have at least 2 countable seizures per month.

- Has not had control with at least 2 anti-seizure medicines.

- Able to maintain a constant medication for duration of the study (rescue meds
allowed).

- Subject or legally authorized representative is able to understand consent and keep a
seizure diary in English.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 3/15/23. Questions regarding updates should be directed to the study team contact.

• Age 18 years and older (no upper age limit defined).
• History of chronic migraine as defined by the International Headache Society’s International Classification of Headache Disorders (3rd edition)8.
• Receiving onabotulinum toxin A injections following a PREEMPT protocol for treatment of chronic migraine for ≥ 1 year.
• Response to therapy with onabotulinum toxin A injections of ≥ 50% improvement in the frequency of headache days when compared to baseline.
• 4 to 14 average number of total headaches days per month during peak efficacy of onabotulinum toxin A injections.
• Ability to understand study procedures and to comply with them for the entire length of the study and use study devices as outlined in protocol.
• Patient agrees to maintain a daily electronic headache diary.
• Proficient in the use of electronic devices including Apple HomeKit and Apple Watch. Subjects owns an iPhone 6s or later with iOS 15 or later operating system installed on iPhone. Apple watch with watch OS6 will be provided by the study.
• Women of childbearing potential shall either be surgically sterile or must agree not to become pregnant for the duration of the study. Subjects of childbearing potential must agree to use a medically approved form of birth control (abstinence, intrauterine device (IUD), oral contraception, barrier and spermicide or hormonal implant) throughout the duration of the study.
• If female, the subject may not be pregnant or breastfeeding. As per routine clinical care, patients who become pregnant while receiving onabotulinum toxin A injections will stop receiving the injections and detection of pregnancy will be guided by routine clinical practice.

• Chronic daily headache with no periods of headache freedom.
• ≥ 15 average number of headaches days per month during peak efficacy of onabotulinum toxin A injections.
• Medication overuse headache as defined by the International Headache Society’s International Classification of Headache Disorders (3rd edition)8.
• Daily opioid use for > 3 months (e.g., hydrocodone, oxycodone, fentanyl patch) or other daily analgesic use for chronic pain disorders (e.g., NSAIDS or acetaminophen).
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/27/22. Questions regarding updates should be directed to the study team contact.

• Patients with a histologic diagnosis of:
  • Newly diagnosed;
  • Progressive;
  • Relapsed lymphoma (any NHL HL, or CLL histology) who are initiating or changing therapy (chemotherapy, radiotherapy, or clinical trial/ investigational agent), or who have measurable disease and are being expectantly monitored. Patients whose lymphoma is in remission and who are being monitored expectantly are eligible as a separate cohort.
• Age > 18 years.
• May be s/p autologous or allogeneic bone marrow transplant.
• Ability to understand and willing to sign a written informed consent document.
• Patients with a histologic diagnosis of relapsed lymphoma or multiple myeloma who are scheduled to undergo CAR T cell therapy (up to 25 patients).
• Newly diagnosed, untreated DLBCL patients confirmed by pathologic review. 

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• Patients already receiving any investigational agents or chemotherapy at time of baseline sample collection.
• Medical illnesses with potential suppressive or activating impact on immune and bowel function as judged by the investigator.                               
• Patients with CNS disease or lymphoma related to prior chemotherapy (new DLBCL cohort only).
• Patients with hemoglobin level of 8 or below.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/17/23. Questions regarding updates should be directed to the study team contact.

• Able to read English fluently.
• Can consent for themselves.
• Age 18 years or older.
• Diagnosis of vestibular schwannoma (also called acoustic neuroma).
• Prior enrollment in IRB protocol 21-003059.

• Lack of capacity to consent since enrollment in IRB protocol 21-003059.
• Unable to participate in an interview by Zoom.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/12/22. Questions regarding updates should be directed to the study team contact.

• Consecutive patients age 18 and older with the below diagnoses:
  • Cervical radiculopathy or cervical myelopathy;
  • Surgical patients eligible for treatment with cervical foraminotomy, cervical arthroplasty, cervical laminectomy, cervical fusion, anterior cervical discectomy and fusion, cervical laminoplasty or a combination of above.

• Individuals < 18 years of age.
• Patients diagnosed at the C1-C2 levels.

Registration
•

• Age ≥ 18 years.
• Histologically or cytologically-confirmed cancer in an advanced incurable stage.
• ECOG Performance Status (PS) 0, 1 or 2.
• Chronic nausea that has been present for at least one week (daily score > 5, on a 0-10 visual analogue scale).
• Serum creatinine < 2.0 mg/dl and SGOT (AST) or SGPT (ALT) values < 3 times upper limits of normal, ≤ 120 days prior to registration.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
• Able to provide written informed consent.
• Able to complete questionnaire(s) by themselves or with assistance.

Registration
•

Any of the following because this study involves:

• An agent that has known genotoxic, mutagenic and teratogenic effects:
  • Pregnant persons;
  • Nursing persons.
• Received chemotherapy or radiation within the prior 14 days (advanced cancer patients receiving hormonal therapy or targeted therapy that does not come with a recommendation for prophylactic anti-emetic therapy are eligible).
• Receiving treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone for ≤ 30 days prior to registration or planned during protocol therapy (patients may have received prochloperazine and other phenothiazines as prior anti-emetic therapy).           
• Those with concurrent use of ethyol; severe cognitive compromise; concurrent use of amifostine; concurrent use of quinolone antibiotic therapy; known hypersensitivity to olanzapine; or have planned chemotherapy or radiation during the 7 days following study initiation.
• Uncontrolled intercurrent illness including, but not limited to:
  • ongoing or active infection (including HIV);
  • cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient;
  • psychiatric illness/social situations that would limit compliance with study requirements.
• Inability to swallow oral formulations of the agent(s).
• Tube feeding or nasogastric tube.

Eligibility last updated 10/27/21. Questions regarding updates should be directed to the study team contact.