Pre-Registration
•

• Age ≥ 18 years.
• Currently have or have had in the past the diagnosis of any type of lymphoma.
• If previously treated, the patient must be off myelosuppressive chemotherapy with no planned chemotherapy for ≥2 months. Patients with lymphoproliferative disorders being observed (i.e., never treated) or those on rituximab (or equivalent) maintenance or chronic oral therapies such as BTK inhibitors, venetoclax, tazemetostat, or corticosteroids are also eligible.
• Able to eat a full range of solid food and liquids and tolerate seeds/nuts.
• ECOG Performance Status (PS) 0, 1, or 2).
• Provide written informed consent.
• Able to recollect dietary intake for the prior 24 hours in order to complete a one-day food record with assistance from a dietitian at each study visit.
• Willing to be seen at the enrolling institution at baseline, and at 4 weeks and 8 weeks (end of treatment) in person or by video/phone.
• Willing to have a blood magnesium checked every 2 weeks x 4 at any Mayo Clinic site.
• Ability to complete questionnaire(s) by themselves or with assistance.

Pre-Registration
•

• Cannot eat normal table food by mouth. 
  • Note: Patients with any form of feeding tube or a swallowing disorder are not eligible.
• Have taken dedicated magnesium supplements (i.e., magnesium oxide) or IV magnesium ≤ 28 days prior to pre-registration.
  • Note: If patient is already on a multivitamin containing -magnesium, they may be enrolled, but the brand should not be changed during the 8 weeks on study.
• Co-morbid systemic illnesses such as active infection 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.
• Patients with significant gut malabsorptive conditions (such as inflammatory bowel disease or others at the discretion of the investigator) will be excluded as well as patients with chronic kidney disease stage 3b or greater (eGFR < 45).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent for lymphoma or any other disease.
• Active other malignancy requiring treatment that would interfere with the assessments of this study.
• Major surgery other than diagnostic surgery ≤ 4 weeks prior to pre-registration.
• Have an allergy to nuts.
• Patients with active skin lymphoma or rashes that would preclude lotion testing.
• Have taken antibiotics ≤ 7 days prior to pre-registration.

Registration -

• The following laboratory value obtained ≤ 5 days prior to registration:
  • Magnesium level of 1.5 – 1.9 mg/dL.

Registration
•

• None.

Eligibility last updated 11/16/21. Questions regarding updates should be directed to the study team contact.

• Male or female, ≥ 10 years of age.
• Diagnosis of Hidradenitis Suppurativa (HS) by a dermatologist or practitioner experienced in making a diagnosis of HS.
• Written informed consent (and assent when applicable) obtained from subject or subject’s legal representative and ability for subject to comply with the requirements of the study.
• Immediate family members (for saliva and genetics data).

• Inability to give informed consent or unavailability of a parent/guardian who is able and willing to give informed consent.

• Age ≥ 18 to ≤ 74 years.
• Able and willing to voluntarily complete the informed consent process.
• Available for and agree to all study procedures, including feces, urine, and blood collection and adherence to diet control, follow-up visits, and compliance with all study procedures.
• Enteric hyperoxaluria secondary to Roux-en-Y bariatric surgery (at least 12 months post-surgery).
• Urinary oxalate ≥ 70 mg/24 hours (mean of at least 2 urine collections during Screening).
• Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an acceptable method of contraception (such as condom with spermicide) combined with an acceptable method of contraception for their non-pregnant female partner(s) (as defined in Inclusion Criterion #7) after informed consent, throughout the study, and for a minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm in the period from Screening until 3 months following administration of the investigational medical product.
• Female subjects who meet 1 of the following:
  • Woman of childbearing potential (WOCBP) must have a negative pregnancy test (human chorionic gonadotropin) at Screening and at baseline prior to the start of IMP and must agree to use acceptable method(s) of contraception, combined with an acceptable method of contraception for their male partner(s) after informed consent, throughout the study and for a minimum of 3 months after the last dose of IMP. Acceptable methods of contraception include hormonal contraception, hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence, vasectomized partner with documented azoospermia 3 months after procedure, diaphragm with spermicide, cervical cap with spermicide, vaginal sponge with spermicide, or male or female condom with or without spermicide.
  • Premenopausal woman with at least 1 of the following:
    • Documented hysterectomy;
    • Documented bilateral salpingectomy;
    • Documented bilateral oophorectomy;
    • Documented tubal ligation/occlusion;
    • Sexual abstinence is preferred or usual lifestyle of the subject.
  • Postmenopausal women (12 months or more amenorrhea verified by FSH assessment and over 45 years of age in the absence of other biological or physiological causes).

Inclusion Criteria
•Part 2:

• Age ≥ 18 to ≤ 74 years.
• Able and willing to voluntarily complete the informed consent process.
• Available for and agree to all study procedures, including feces, urine, and blood collection and adherence to diet control, follow-up visits, and compliance with all study procedures.
• Enteric hyperoxaluria secondary to history of malabsorption after bariatric surgery or surgical short-bowel syndrome.
• Urinary oxalate ≥ 45 mg/24 hours (mean of 2 samples during screening). (Tier 1 urinary oxalate must be ≥ 40 mg/24 hours to be eligible for Tier 2 screening).
• If taking probiotic supplements (enriched foods excluded), has been on stable, well-tolerated dose for at least 2 weeks prior to Day 1.
• Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an acceptable method of contraception (such as condom with spermicide) combined with a recommendation for use of an acceptable method of contraception for their non-pregnant female partner(s) after informed consent, throughout the study, and for a minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm in the period from screening until 3 months following administration of the investigational medical product.
• Female subjects who meet 1 of the following:
  • WOCBP must have a negative pregnancy test (human chorionic gonadotropin) at screening and at baseline prior to the start of IMP and must agree to use acceptable method(s) of contraception, combined with a recommendation for use of an acceptable method of contraception for their male partner(s) after informed consent, throughout the study and for a minimum of 3 months after the last dose of IMP. Acceptable methods of contraception include hormonal contraception, hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence, vasectomized partner with documented azoospermia 3 months after procedure, diaphragm with spermicide, cervical cap with spermicide, vaginal sponge with spermicide, or male or female condom with or without spermicide;
  • Premenopausal woman with at least 1 of the following:
  • Documented hysterectomy;
  • Documented bilateral salpingectomy;
  • Documented bilateral oophorectomy;
  • Documented tubal ligation/occlusion;
  • Sexual abstinence is preferred or usual lifestyle of the subject c. Postmenopausal women (12 months or more amenorrhea verified by FSH assessment and over 45 years of age in the absence of other biological or physiological causes).
• Screening laboratory evaluations (e.g., chemistry panel, complete blood count with differential, prothrombin time [PT]/activated partial thromboplastin time [aPTT], urinalysis) and electrocardiogram (ECG) must be within normal limits or judged to be not clinically significant by the investigator. A single repeat evaluation is acceptable.

• Acute or chronic medical (including COVID-19 infection), surgical, psychiatric, or social condition or laboratory abnormality that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of study safety or PD results and, in the judgment of the investigator, would make the subject inappropriate for enrollment.
• Acute renal failure or estimated glomerular filtration rate <45 mL/min/1.73 m2.
• Unable or unwilling to discontinue vitamin C supplementation for the study duration
• Diagnosis of primary hyperoxaluria or any other cause of hyperoxaluria.
• Pregnant (self or partner), or lactating.
• Taking any type of systemic (e.g., oral or intravenous) antibiotic within less than 5 times the halflife of the antibiotic prior to Day 1.
  • Exception: topical antibiotics are allowed.
• Major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay within the past 3 months prior to screening.
• Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 30 days prior to Day 1 through the final safety assessment.
  • Exception: topical antibiotics are allowed.
• Major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay within the past 3 months prior to Screening.
• Planned surgery, hospitalizations, dental work, or interventional studies between Screening and last anticipated visit.
• Intolerance of or allergic reaction to EcN or any of the ingredients in SYNB8802 or placebo formulations.
• Dependence on alcohol or drugs of abuse.
• History of or current immunodeficiency disorder including autoimmune disorders and HIV antibody positivity.
• Hepatitis B surface antigen positivity (subjects with hepatitis B surface antibody positivity and hepatitis B core antibody positivity are not excluded, provided that the hepatitis B surface antigen is negative).
• Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is performed, and the result is negative.
• Administration or ingestion of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to Screening Visit; or current enrollment in an investigational study.
• History of bacteremia within 30 days prior to the anticipated first dose of IMP.
• History of inflammatory bowel disease.

Eligibility last updated 2/1/22. Questions regarding updates should be directed to the study team contact.

• Diagnosed with a CNS hypersomnia according to ICSD-3 classifications.
• Age 18
  •75 years.
• BMI between 18 and 40 kg/m^2.
• Prescribed a medication of interest (e.g., sodium oxybate, low sodium oxybate, pitolisant, modafinil/armodafinil, solriamfetol) by a clinical sleep specialist as part of routine medical care and covered by subject’s health insurance plan.
• If subject has not yet started the prescribed medication, then subject must be willing to postpone starting medication until after completion of baseline assessment(s).
• If subject has been taking a prescribed medication at a stable dose for at least 3 months and has been prescribed a new medication, then then subject may complete baseline assessment(s) while taking initial medication before starting new medication.

• Any change to medication(s) within the last 45 days.
• History of chronic alcohol or drug abuse within the prior 12 months.
• Heart failure, history of severe hypertension, or other cardiovascular disease compromising the patient's wellbeing or ability to participate in this study.
• Use of any sleep apnea treatment (e.g., Positive Airway Pressure (PAP) therapy, oral appliance therapy, etc.) within 45 days of baseline assessment visit.
• Participation in another study of an investigational drug within the 28 days prior to screening visit or currently.
• Pregnancy and/or breast-feeding.
• Subjects who, in the opinion of the Investigator, may not be suitable for the study.                     

Eligibility last updated 4/28/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Patients:

• Adults ≥ 18 years
• Appointment to discuss osteoporosis management

Exclusion Criteria
•Patients:

• Major barriers to providing informed consent (i.e. dementia, severe hearing or visual impairment)

Inclusion Criteria
•Clinicians:

• Clinicians who meet with patients to discuss osteoporosis management.

Exclusion Critieria
•Clinicians:

• None

Inclusion Critieria
•PAG Members:

• Adults ≥ 18 years
• Member of the Knowledge and Evaluation Research (KER) Unit Patient Advisory Group (PAG)

Eligibility last updated 1/18/22. Questions regarding updates should be directed to the study team contact.

• All patients 18 years of age and older undergoing (or who have previously undergone) EpiAcc as part of their standard clinical care for an electrophysiology procedure. Patients will not undergo EpiAcc purely for the research study.

• Patients undergoing EpiAcc for the purposes of a pericardiocentesis.

• Subject has biopsy-proven papillary or follicular thyroid cancer.
• Subject is indicated for 123I-SPECT/CT total body iodine (TBI) scan.
• Subject agrees to undergo 18F-TFB PET/CT scan following TBI scan.
• Karnofsky performance status of greater than or equal to 50 (or ECOG/WHO equivalent).
• Subject is able to be scanned
  •able to lie still on SPECT/CT and PET/CT scanner table for up to 65 min.
• Age years 18 or older.
• Ability to understand a written informed consent document, and the willingness to sign it.
• Subject is not pregnant.

• Contrast-enhanced CT within 4 last weeks.
• Amiodarone within last 4 months.
• Ingested iodine, kelp tablets, Lugols iodine, or SSKI within 2 weeks. If questionable, then urinary iodine measurement must be performed. Exclude if 24h urinary iodine > 100 microg/d.
• Unable to lie flat, still or tolerate a PET scan.
• Applied betadine, iodoform, or quick tanning products to skin within last two weeks.
• If using medication withdrawal for stimulation, then exclude if TSH level < 25.
• Taken anti-thyroid medication within 1 week.
• Subject is breastfeeding.
• Positive pregnancy test.

• Healthy adults, age 50 and over.

• Individuals with a FRAIL score of 3 or greater.
• Have experienced a prior osteoporotic fracture.

• Males or females, ≥ 18 years old.
• Recently underwent parotidectomy at Mayo Clinic Rochester (range: 1 day – 1 year).
• Surgical indication for benign and malignant tumors.

• No concurrent surgeries at the time of parotidectomy.
• No prior parotid surgery.
• No adjuvant radiotherapy or chemotherapy after parotidectomy and before this survey.
• History of Bell’s palsy or other cause of facial nerve dysfunction.
• History of facial cosmetic surgery (EXCEPT rhinoplasty).
• History of chronic salivary disease.

• Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject is ≥ 18 years of age at the time of signing the ICF.
• Relapsed or refractory CD33 positive AML at last visit by local assessment as defined by the World Health Organization (WHO) Classification who have failed or who are ineligible for or have refused all available therapies for AML which may provide clinical benefit.
• Subjects who have received prior treatment with a CD33-targeted therapy may be included in the study. 6. Subject has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion without conditioning.
• Subjects must have the following screening laboratory values:
  • Total White Blood Cell count (WBC) < 25 x 10^9 /L prior to first infusion. Treatment with hydroxyurea to achieve this level is allowed;
  • Potassium, calcium (corrected Ca or free [ionized] Ca), and magnesium within normal limits or correctable with supplements;
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, in which case AST and ALT can be ≤ 5.0 x ULN;
  • Uric acid ≤ 7.5 mg/dL (446 μmol/L). Prior and/or concurrent treatment with hypouricemic agents (e.g., allopurinol, rasburicase) are allowed;
  • Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome (e.g., a gene mutation in UGT1A1), in which case serum total bilirubin must be ≤ 3.0 mg/dL;
  • Estimated serum creatinine clearance of ≥ 50 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated;
  • International normalized ratio (INR) < 1.5 x ULN and aPTT < 1.5 x ULN (for subjects not receiving therapeutic anticoagulation);
  • Platelets (plts) ≥ 15,000/µL with transfusions allowed;
  • Hemoglobin (Hgb) ≥ 7 g/dL with transfusions allowed.
• Females of childbearing potential (FCBP)* must:
  • Either commit to true abstinence** from heterosexual contact or agree to use, and be able to comply with, at least one highly effective method of contraception (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; or vasectomized partner), from signing the ICF, throughout the study, including during dose interruptions, and for at least 105 days following the last dose of CC-96191. The selected contraceptive method will be reviewed and evaluated on a monthly basis, and this will be noted in source documents; and
  • Have two negative pregnancy tests as verified by the Investigator prior to starting CC-96191. She must agree to ongoing pregnancy testing during the course of the study, through 105 days following treatment discontinuation. This applies even if the subject practices true abstinenceb from heterosexual contact. The subject may not receive IP until the Investigator has verified that the result of the pregnancy test is negative;
  • Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at Screening;
  • Have a negative serum or urine pregnancy test (Investigator’s discretion) within 72 hours prior to the first dose (Cycle 1 Day 1) of study treatment, and within 72 hours prior to Day 1 of every subsequent cycle (note that the Screening serum pregnancy test can be used as the test prior to Day 1 study treatment if it is performed within the prior 72 hours). A serum or urine pregnancy test (investigators discretion) must also be performed at treatment discontinuation and at 105 days following treatment discontinuation;
  • Avoid conceiving for 105 days after the last dose of CC-96191;
  • Agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. This applies even if the subject practices true abstinenceb from heterosexual contact.
• Males must practice true abstinence** (which must be reviewed, evaluated and source documented on a monthly basis) or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or a FCBP and will avoid conceiving from signing the ICF, while participating in the study, during dose interruptions, and for at least 105 days following CC-96191 discontinuation, even if he has undergone a successful vasectomy. *A female of childbearing potential is a sexually mature woman who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months).
• **True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].

• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition; e.g., active or uncontrolled infection, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subjects with previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1:
  • Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the subject at a higher risk of receiving study treatment.
• Previous SARS-CoV-2 vaccine within 14 days of C1D1. For vaccines requiring more than one dose, the full series (e.g., both doses of a two-dose series) should be completed by at least 14 days prior to C1D1 when feasible and when a delay in C1D1 would not put the study subject at risk.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject is suspected or proven to have acute promyelocytic leukemia (FAB M3) based on morphology, immunophenotype, molecular assay, or karyotype.
• Subject has received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of study treatment. Hydroxyurea is allowed to control peripheral leukemia blasts.
• Subjects with prior autologous hematopoietic stem cell transplant who, in the investigator’s judgment, have not fully recovered from the effects of the last transplant (e.g., transplant-related side effects).
• Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing.
• Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of topical steroids for ongoing skin or ocular GVHD is permitted.
• Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2.
• Subject has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening.
• Subject has immediate life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation. The subject should be afebrile for at least 72 hours.
• History of concurrent second cancers requiring active, ongoing systemic treatment.
• Subject is known seropositive or active infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus or hepatitis C virus.
• Subject with a positive SARS-CoV-2 test during Screening will be required to delay dosing for a minimum of 10 days from the last positive test or resolution of symptoms, whichever is longer.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
  • Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO);
  • Complete left bundle branch or bifascicular block;
  • Congenital long QT syndrome;
  • Persistent or clinically meaningful ventricular arrhythmias;
  • QT interval with Fridericia’s correction (QTcF) ≥ 470 msec on Screening electrocardiogram (ECG) (mean of triplicate recordings);
  • Unstable angina or myocardial infarction ≤ 3 months prior to starting CC-96191;
  • Congestive heart failure (New York Heart Association Class III or IV) ≤ 12 months prior to the first dose of CC-96191.
• Subject is a pregnant or lactating female.
• Prior live virus vaccines within at least 4 weeks prior to starting study drug.
• Subject has known or suspected hypersensitivity to any of the components or any of the excipients of the study treatment.

Eligibility last updated 2/7/22. Questions regarding updates should be directed to the study team contact.

• Patient must have the ability to understand and the willingness to sign a written informed consent document.
• Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
• Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 60 days prior to registration with one of the following:
  • Upper urinary tract mass on cross-sectional imaging; or
  • Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology;
    • NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice.
  • Leukocytes ≥ 3,000/mcL (obtained ≤ 14 days prior to registration);
  • Platelets ≥ 100,000/mcL (obtained ≤ 14 days prior to registration);
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2.5 x ULN for patients with Gilbert's disease) (obtained ≤ 14 days prior to registration);
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (obtained ≤ 14 days prior to registration);
  • Hemoglobin (Hgb) ≥ 9 g/dL (obtained ≤ 14 days prior to registration);
    • NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial;
    • NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.
    • NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count ≥ 250 cells/mcL within 7 days of registration.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Patient must have a body weight of > 30 kg.
• Patient must have a life expectancy of ≥ 12 weeks.
• Patient must have a creatinine clearance > 15 ml/min as by Crockroft-Gault or 24-hour creatinine clearance within 28 days prior to registration.
  • NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and hearing loss in keeping with SOC cisplatin contraindications.
• Patients that are cisplatin-eligible will be randomized to either Arm A or Arm B.
• Patients that meet the following criteria will be assigned to the cisplatin-ineligible Arm C:
  • Creatinine clearance of > 15 ml/min and ≤ 50 ml/min;
  • Patient must have an absolute neutrophil count (ANC) ≥ 1,000/mcL obtained ≤ 14 days prior to registration;
  • Patient must have ECOG performance status 0-2.
• Patients that meet the following criteria will be randomized to cisplatin-eligible Arm A or Arm B:
  • Patient must have an absolute neutrophil count (ANC) ≥ 1,500/mcL obtained ≤ 14 days prior to randomization;
  • Patient must have ECOG performance status 0-1;
  • Patient must have left ventricular ejection fraction (LVEF) ≥ 50% by (either multigated acquisition scan [MUGA] or 2-D echocardiogram) obtained within 28 days prior to randomization;
  • Patient must not have peripheral neuropathy ≥ grade 2 or hearing loss ≥ grade 3.

• Patients must not have any component of small cell carcinoma. Other variant histologic types are permitted provided the predominant (≥ 50%) subtype is urothelial carcinoma.
• Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
  • Has achieved menarche at some point;
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months);
  • Patients of childbearing potential and sexually active patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment.
• Patient must have no evidence of metastatic disease or clinically enlarged lymph nodes (≥ 1.0 cm short axis) on imaging required within 28 days prior to registration (solitary slightly enlarged lymph node with negative biopsy is allowed).
  • NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness should also undergo baseline bone scans to evaluate for bone metastasis.
• Patient must not have another active (or within 2 years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g., ≤ Gleason 3+4) on surveillance or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat.
  • NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients in whom concomitant or prior bladder/urethra predominant (≥ 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed.
• Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) in last 3 months, or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient must not have received prior radiation therapy to ≥ 25% of the bone marrow for other diseases.
• Patient must not have received prior systemic anthracycline therapy.
  • NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible.
• Patient must not have an active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration or a history of inflammatory bowel disease (inflammatory bowel disease [IBD], colitis, or Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, Wegener syndrome or immune-related pneumonitis or interstitial lung disease.
• Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diverticulosis, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition.
• Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of MEDI4736 (MEDI4736 (durvalumab). The following are exceptions to this criterion:
  • Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g., intra-articular injection;
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment;
  • Steroids as premedications for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication);
  • Patient must not have a concomitant primary urothelial carcinoma of the bladder and/or urethra;
  • NOTE: Patients in whom concomitant or prior bladder/urethra predominant (≥ 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed.
• Patient must not have prior history of muscle-invasive urothelial carcinoma with or without systemic chemotherapy (T2-4a and/or N1) within 2 years prior to registration.
  • NOTE: Patients who have no evidence of disease (NED) for more than 2 years from the latest therapy (surgery, radiation, chemotherapy, or clinical trial).
• Patient must not have received live attenuated vaccine within 30 days prior to the first dose of MEDI4736 (durvalumab), while on protocol treatment and within 30 days after the last dose of MEDI4736 (durvalumab).
• Patient must not have had a major surgical procedure (as defined by the Investigator) within 28 days prior to registration.
• Patient must not have a history of allogenic organ transplantation.

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

Eligibility last updated 5/16/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria:

• Greater than or equal to 18 years of age.
• Diagnosis of a solid tumor malignancy.
• Enrollment and participation in a phase I clinical trial at the Mayo Clinic Early Cancer Therapeutics Clinic for at least 2 month.

• Enrollment in a phase I clinical trial for a hematologic malignancy.
• Inability to speak English.

• Age ≥ 18, Age ≤ 100.
• Patients having undergone total knee arthroplasty with highly congruent or posterior stabilized designs(DJO 3D Empowr vs Zimmer MP vs PS Stryker primary TKA).

• No vulnerable populations.

Eligibility last updated 10/28/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria - Phase 1:

AIAN Women

• AIAN based on self-reported race.
• Gender identity as a woman.
• Resides in Minnesota.
• At least 18 years of age age with no upper age limit.
• OUD based on the DSM-5 Checklist (American Psychiatric Association, 2013).
• Self-reports at least one month of opioid abstinence based on Timeline Follow-Back (TLFB) interview.
• Currently receiving MOUD.
• Is comfortable speaking and reading English.
• Is familiar with Facebook.
• Has access to broadband internet on a mobile phone/computer/tablet at any location.
• OUD, if other substance use, opioids are primary substance used.
• Self-reports at least one month of opioid abstinence based on TLFB interview.
• Currently receiving MOUD.
• Is comfortable speaking and reading English.
• Has an existing FB account or willing to create a FB account.
• Has access to broadband internet on a mobile phone/computer/tablet at any location.
• Willing and able to travel to Minneapolis, MN.

AI/AN Health Care Providers and Stakeholders

• Health care provider or AIAN community stakeholder.
• Knowledge of Native culture and/or OUD treatment and recovery among AIAN people.
• Is comfortable speaking and reading English.
• Is familiar with Facebook.
• Has access to broadband internet on a mobile phone/computer/tablet at any location.

Inclusion Criteria
•Phase 3:

• AIAN person based on self-reported race/ethnicity.
• Gender identity as a woman.
• At least 18 years of age.
• Resides in MN.
• OUD based on the DSM-5 Checklist (American Psychiatric Association, 2013).
• Self-reports at least one month of abstinence from opioid use based on TLFB interview and negative urine opiate screen.
• Currently receiving MOUD.
• Is comfortable speaking and reading English.
• Has an existing Facebook account or willing to set one up.
• Is willing and able to participate in the Facebook intervention for one month.
• Has access to broadband internet on a mobile phone/computer/tablet at any location.
• Is willing and able to travel to a community clinic in Minneapolis, Minnesota for the UDS.

AIAN potential participants in Phases 1 and 3 meeting any of the exclusion criteria listed below will be excluded from study participation. Community stakeholder participants in Phase 1 will only fail the screening if they meet the second exclusion criterion:

• Self-reports current suicidality.
• Inability or unwillingness of participant to provide verbal consent (Phase 1) or written informed consent (Phase 3).
• (Phase 3 only) Was a participant in Phase 1.

Pregnant women, lactating women, or women who plan to become pregnant will not be excluded because the treatment being evaluated is a behavioral intervention and does not involve medication or risk to the fetus.

Eligibility last updated 3/14/22. Questions regarding updates should be directed to the study team contact.

• Is 18 years old or older.
• Self-identifies as a member of the LGBTQ community or self-identified as such at the time of their admission or is the spouse, partner, or family member who identifies as a member of the LGBTQ community.
• Has been on a ventilator in the intensive care unit or is the spouse, partner, or family member of a patient on a ventilator in the intensive care unit between 1/2016 and 2/2022.

• Does not meet the above criteria for age, LGBTQ identity, relationship to an LGBTQ identifying individual, and past mechanical ventilation.

Eligibility last updated 3/2/22. Questions regarding updates should be directed to the study team contact.

• Patient with a class I or IIa (1) or (2) indication for implantation of a CRT device according to current available guidelines (with additional QRS criteria on Class IIa (1)):
  • Class I: NYHA II, III, IV, EF ≤ 35%† , LBBB, QRS ≥ 150ms‡;
  • Class IIa (1): NYHA II, III, IV, EF≤ 35%† , LBBB, QRS ≥ 130 to < 150ms‡;
  • Class IIa (2): NYHA II, III, IV, EF≤ 35%†, non-LBBB, QRS ≥ 150ms‡.
• Patient is a:
• ‘Non-responder’ (Part I and Part II
  •Roll-in and Randomized Only): [This criterion is not applicable to Part III Single-arm]
  • Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:
    • EF has remained unchanged or worsened (defined as < 5% increase since implant); and
    • The patient’s clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee; OR
  • ‘Previously Untreatable’ (Part I, Part II, and Part III- Roll-in, Randomized, and Single-arm):
    • Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as ‘previously untreatable’ for one of the following reasons:
    • Patients in whom CS lead implantation for CRT has failed:
      • CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges;
    • CS lead implanted but has been programmed OFF§,
      • LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, noncapture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location; OR
  • ‘High Risk Upgrade’ (Part I, Part II, and Part III):
    • Patients in whom standard CRT upgrade is not advisable due to known relative contraindication to CS lead implant, for example:
    • Risk of venous occlusion or lesion precluding implant (e.g., multiple existing leads in situ);
    • Risk of pocket infection at co-implanted device site (e.g., co-implant placement or battery change within last 12 months);
    • Considered high risk for CS implant due to co-morbidities (e.g., history of ICM or VT with risk of epicardial pacing induced VT).
• Patients on a stable Guideline Directed Medical Therapy (GDMT).
• Patient must be 18 years old or over.
• Patient has signed and dated informed consent.
• Patient has suitable anatomy for implant of the WiSE CRT System (e.g., adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant).

† EF used for inclusion criteria and for the Baseline TTE must be measured under these conditions:

• Non-responder Patients: EF measured with BiV ON;
• Previously Untreatable Patients: EF measured with CS Lead OFF (if it exists), or in baseline state (if CS lead does not exist);
• High Risk Upgrade Patients: EF measured in baseline state.

‡ QRS used for inclusion criteria should be measured as the patient presents: Non-responder Patients: BiV QRS, Previously untreatable, high risk upgrade – either intrinsic or RV QRS – patient in their current, optimized state.

§ The CS Lead must be programmed OFF during SOLVE CRT screening.

• Pure RBBB.
• LVEDD ≥ 8cm.
• Non-ambulatory or unstable NYHA class IV.
• Contraindication to heparin, chronic anticoagulants, or antiplatelet agents.
• Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy.
• Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
• Patients with planned or expected lithotripsy treatment post implant.
• Life expectancy of < 12 months.
• Chronic hemodialysis.
• Stage 4 or 5 renal dysfunction defined as eGFR < 30.
• Grade 4 mitral valve regurgitation.
• Noncardiac implanted electrical stimulation therapy devices.
• Patients with a prosthetic aortic valve and a non-viable transseptal approach for the electrode implant.
• Patients with a prosthetic mitral valve and a non-viable retrograde aortic approach for the electrode implant.
• Unstable angina, acute MI, CABG, or PTCA within the past 1 month.
• Correctable valvular disease that is the primary cause of heart failure.
• Recent CVA or TIA (within the previous 3 months).
• Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 30 days from screening.
• Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing < 95%).
• Already included in another clinical study that could confound the results of this study.
• Pregnancy.
• Known drug or alcohol addiction or abuse.
• Moderate or severe aortic stenosis.
• Positive test for COVID-19 at screening.
• Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures.
• For Part II randomized patients, those who will not tolerate being randomized to the Control Group for 6 months.

Eligibility last updated 6/30/22. Questions regarding updates should be directed to the study team contact.

• Advanced heart failure.
• Southeastern Minnesota resident

• None.

• Age ≥ 18 years.
• Histological or cytological confirmation of brain tumor and/or suspected brain tumor based on clinical and radiologic findings.
• Prior chemotherapy and/or radiation treatment directed to the known/suspected tumor.
• Radiographic evidence of residual or previously unresected tumor.
• Willingness to undergo surgery and sign informed consent.
• Patients not currently eligible for an alternate competing interventional clinical trial.
• Enrollment in the Mayo Clinic Cancer Center Neuro-Oncology Program Registry for the study of Nervous System Tumors (IRB#12-003458)

• Age < 18 years.
• Prior gross total resection of brain tumor leading to absence of visible latent disease (exemption available for post-operative enrollment).
• Any contraindication to surgery, including anyone who in the opinion of the surgeon is at unreasonably elevated risk of wound complications.
• Avastin within the past 6 months for any reason.
• Patients who have not yet undergone surgery or radiation, but who would be appropriate candidates for an alternate interventional clinical trial (e.g., post-operative fractionated vs. single fraction radiation to the surgical cavity for surgical brain mets).

• ≥ 18 years of age.
• Able to provide informed consent.
• Individual must have a future treatment plan to receive or has historically received phage therapy.

• Individuals , 18 years of age.
• Unwilling/unable to provide informed consent.

Eligibility last updated 1/10/22. Questions regarding updates should be directed to the study team contact.

• 22- 65 years of age.
• Current diagnosis of T2D.
• History of T2D for at least 3 years and less than or equal to 10 years.
• HbA1C of 7.5-10.0%, inclusive.
• BMI 24-40 kg/m^2, inclusive.
• On two to three non-insulin glucose lowering mediations, with one at maximum tolerated dose and another at half-maximum dose at least, with no changes in medication for at least 12 weeks prior to baseline visit prior to baseline visit.
• History of failed attempt to reach glycemic goal by lifestyle modifications.
• Weight stability (defined as a < 5% change in body weight) for at least 12 weeks prior to the screening visit.
• Agree not to donate blood during participation in the study.
• Able to comply with study requirements and understand and sign the Informed Consent Form.
• Women of childbearing potential must be using an acceptable method of contraception throughout the study.
• Willing and able to use CGM for the duration of the study and comply with study visits and study tasks as required per protocol.
• Proof of COVID 19 vaccination.

• Diagnosed with type 1 diabetes.
• History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
• Probable insulin production failure, defined as overnight fasting C-peptide serum <1 ng/mL (333pmol/l).
• Previous use of any types of insulin for > 1 month (at any time, except for treatment of gestational diabetes) in last 2 years.
• Current use of insulin.
• Hypoglycemia unawareness.
• History of ≥1 severe hypoglycemia episode (defined by needing for third-party assistance) in past 6 months from the screening visit.
• Known autoimmune disease, as evidenced by a positive anti-glutamic acid decarboxylase (GAD) test, including but not limited to celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder. (Participants with adequately controlled primary hypothyroidism may be included).
• Previous GI surgery that has changed GI anatomy or could limit treatment of the duodenum, such as Billroth 2, Roux-en-Y gastric bypass, gastric band or other similar procedures or conditions.
• Known history of a structural or functional disorder of the upper GI tract that may impede passage of the device through the upper GI tract or increase risk of tissue damage during an endoscopic procedure, including esophagitis, stricture/stenosis, varices, diverticula, or other disorder of the esophagus, stomach and duodenum.
• Active H. pylori infection (Participants with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen).
• History of, or gastrointestinal symptoms suggestive of gastroparesis.
• Acute gastrointestinal illness in the previous 7 days.
• Known history of irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease and Celiac disease.
• History of chronic or acute pancreatitis.
• Known active hepatitis or active liver disease other than NASH/NAFLD.
• Alcoholic liver disease, as indicated by ANI > 0.
• Current use of anticoagulation therapy (such as warfarin) that cannot be discontinued for 7 days before and 14 days after the procedure.
• Current use of P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) that cannot be discontinued for 14 days before and 14 days after the procedure.
• Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of acetaminophen and low dose aspirin is allowed.
• Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 12 weeks prior to the baseline visit.
• Use of drugs known to affect GI motility (e.g., Metoclopramide).
• Use of weight loss medications such as Meridia, Xenical, Phentermine or over-the-counter weight loss medications (prescription medication).
• Currently taking, or unable to stop taking dietary supplements or herbal agents, including vitamin C or multivitamins containing vitamin C at > 500 mg per day, multivitamins containing biotin (vitamin B7), and supplements for hair, skin, and nail growth. Multivitamins not containing biotin are permitted.
• Persistent anemia, defined as hemoglobin < 10 g/dL.
• Known history of hemoglobinopathy.
• Known history of blood donation or transfusion within 3 months prior to the Screening Visit.
• Known history of cardiac arrythmia.
• Significant cardiovascular disease, including known history of valvular disease, or myocardial infarction, heart failure, transient ischemic attack, or stroke within 6 months prior to the Screening Visit.
• Estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73m^2 (estimated by MDRD).
• Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months, who have clinically significant leukopenia, who are positive for the human immunodeficiency virus (HIV) or whose immune status makes the participant a poor candidate for clinical trial participation in the opinion of the investigator.
• History of secondary hypothyroidism or inadequately controlled primary hypothyroidism (TSH value outside the normal range at screening).
• With any implanted electronic devices or duodenal metallic implants
• Not a candidate for upper GI endoscopy or general anesthesia.
• Active illicit substance abuse or alcoholism (> 2 drinks/day regularly).
• Active malignancy within the last 5 years (excluding non-melanoma skin cancers).
• Women breastfeeding.
• Participating in another ongoing clinical trial of an investigational drug or device.
• Any other mental or physical condition which, in the opinion of the study investigator, makes the participant a poor candidate for clinical trial participation.
• Critically ill or has a life expectancy < 3 years.
• Additional exclusion criteria to be confirmed during the screening process:
  • HbA1c < 7.5% or > 10% at baseline visit;
  • Any severe hypoglycemic event since the screening visit;
  • CGM readings < 54 mg/dl in more than 1% of time by CGM since the screening visit;
  • CGM readings > 360 mg/dL in more than 1% of time.
  • Mean of 3 separate blood pressure measurements > 180 mmHg (systolic) or > 100 mmHg (diastolic).
• Women of child-bearing potential with a positive urine pregnancy test at baseline visit.
• LA Grade C or greater esophagitis on endoscopy.
• Abnormalities of the GI tract preventing endoscopic access to the duodenum.
• Anatomic abnormalities in the duodenum that would preclude the completion of the treatment procedure, including tortuous anatomy.
• Endoscopic observation of upper gastrointestinal abnormality such as ulcers, polyps, varices, strictures, congenital or intestinal telangiectasia.
• Any other anatomical or endoscopic abnormalities/characteristics that, in the opinion of the investigator, would preclude safe use of the investigational device or procedure.

• Aged 18 years or older.
• Outpatient or inpatient status.
• Patients who have been clinically referred for ECT and completed the clinical informed consent process for ECT.
• Patients who had the capacity to consent for ECT independently on a voluntary basis.
• Healthy control patients will be aged 18 years or older and have the capacity to consent for the research study.

• Patients who are undergoing court ordered ECT are not eligible for the study.
• Patients who did not have the capacity to consent for clinical ECT are not eligible.
• Patients who in the opinion of the clinical principal investigator (Dr. Croarkin) or a psychiatrist study team member are not able to consistently wear the Garmin device or complete protocol related activities.
• Healthy control patients who have active psychiatric symptoms based on an interview with the principal investigator (Dr. Croarkin) or a psychiatrist study team member are not eligible to participate. 

• Patient presenting to a General Internal Medicine Service.
• Patient in one of the 3 Mayo Clinic Campuses (Rochester, Arizona, Florida).
• Patient with an undiagnosed mass: New or enlarging lymph nodes clinically or on imaging:
  • New mass on imaging of soft tissues, bone, spleen, adrenal gland, retroperitoneum, or intraabdominal location without clear organ association.
• Patient has understood and signed the informed consent to participate in the registry.
• Patient has the ability to complete all aspects of registry enrollment.
• Aged 18 and older.

• Mass involving the breast, brain, kidney, lung, ovary/adnexa, liver, pancreas, sinus, throat, or thyroid gland will be addressed by the respective specialty areas.  
• Patients with a known history of any condition or factor judged by the investigator to preclude participation in the registry or which might hinder adherence.
• Lacking the capacity to consent.
• Prisoners or institutionalized individuals.
• Pregnant women.

Eligibility last updated 9/17/21. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 5/9/23. Questions regarding updates should be directed to the study team contact.

• Participants must have a histologic diagnosis of well-differentiated pancreatic neuroendocrine tumor (pNET) that was resected between 14 and 90 days prior to registration. Participants must have a scan within 90 days prior to registration without evidence of metastatic disease. Acceptable scans are multiphase computed tomography (CT) abdomen, magnetic resonance imaging (MRI) with intravenous (IV) contrast of the abdomen, or positron emission tomography (PET)-CT DOTATATE imaging if the DOTATATE PET-CT included IV iodine contrast for the CT portion of the exam.
• Resection must have been an R0 or R1 per treating investigator's assessment and/or pathology report.
• Ki-67 testing, which is considered part of standard of care in the pathology report, must have been performed between 14 and 90 days prior to registration and the result must be ≥ 3% and ≤ 55%. Treating investigators are encouraged to contact the S2104 Study Chairs and/or the study pathology chair with questions. If more than one Ki-67 is reported (e.g., primary tumor versus lymph node or metastatic site), the highest one should be considered for the study eligibility criteria.
• Participants with localized resected pNETS must have a Zaidi score of ≥ 3 derived by the following factors and points:
  • 1 point; symptomatic tumor defined as one of the following:
    • Gastrointestinal bleed;
    • Jaundice;
    • Gastrointestinal obstruction;
    • Pain from primary tumor prior to surgical resection;
    • Pancreatitis.
  • 2 points; primary pancreas tumor size > 2 cm.
  • 1 point; Ki-67 3% to 20% -1 point; lymph node positivity = 1.
  • 6 points; Ki-67 21% to 55%.
• Participants may have received resection/ablation of liver oligo-metastatic disease (up to 5 liver metastases) at the time of well-differentiated pNET resection.
• Participants must not have unresected or unablated metastatic disease.
• Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis.
• Participants must have recovered from effects of surgery as determined by the treating investigator.
• Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted.
• Participants must not have received somatostatin analogs after surgery.
• Participants must be ≥ 18 years old
• Participants must have Zubrod performance status of 0-2
• Participants must have a complete medical history and physical exam within 28 days prior to registration.
• Patients must have adequate organ and marrow function as defined below within 28 days prior to registration:
  • Leukocytes ≥ 3 x 10^3/uL (within 28 days prior to registration);
  • Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days prior to registration);
  • Platelets ≥ 100 x 10^3/uL (within 28 days prior to registration);
  • Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to registration);
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN (within 28 days prior to registration);
  • Serum creatinine ≤ 1.5 x institutional ULN (within 28 days prior to registration);
  • Calculated creatinine clearance ≥ 50 ml/min (within 28 days prior to registration).
  • Calculated Creatinine Clearance = (140
    •age) X (weight in kg) † 72 x serum creatinine:
  • * Multiply this number by 0.85 if the participant is female.
  • † The kilogram weight is the participant weight with an upper limit of 140% of the IBW.
  • * Actual lab serum creatinine value with a minimum of 0.8 mg/dL.
• Participants must be able to swallow pills.
• Participants must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol.
• Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed.
• Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine.
• Participants must not have known absorption issues that would limit the ability to absorb study agents.
• Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration.
• Participants must not have active or uncontrolled infection.
• Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator.
• Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential."In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.
• No other active malignancy or history of prior malignancy is allowed, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years.
• Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.

• Participants must not have unresected or unablated metastatic disease.
• Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis.
• Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted.
• Participants must not have received somatostatin analogs after surgery.
• Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed.
• Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine.
• Participants must not have known absorption issues that would limit the ability to absorb study agents.
• Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration.
• Participants must not have active or uncontrolled infection.
• Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator.
• Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.

Eligibility last updated 12/27/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 0/6/23. Questions regarding updates should be directed to the study team contact.

Phase 1:

• Diagnosis of higher risk MDS that is either previously untreated or relapsed/refractory.

Phase 2:

• Diagnosis of higher risk MDS that is previously untreated.
• Adequate renal and liver function.
• Age ≥ 18 years.
• Adequate performance status.

• Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) for MDS or AML.
• Prior treatment with any anti-CD47 or anti-SIRPα (signal regulatory protein alpha) agent.
• Known active viral infections, including hepatitis B and C, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) related illness, or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).

Eligibility last updated 2/22/23 to match clinicaltrials.gov. Questions regarding updates should be directed to the study team contact.