Registration
•Inclusion Criteria

• Age ≥ 18 years.
• Diagnosed with cancer and receiving chemotherapy.
• Able to provide informed consent.
• Willingness to complete questionnaires.
• ECOG Performance Status (PS) 0, 1, 2.
• One or more of the following nasal symptoms for which the patient reports they would appreciate treatment. Symptoms must have started after the initiation of systemic, antineoplastic therapies, be attributed to the systemic, antineoplastic therapies, and symptoms must be reported  as being moderate (corresponding to a score of 2) or worse on a scale from mild (1) to very severe (4) on at least one of the items below.
• Dryness;
• Discomfort/Pain;
• Bleeding;
• Scabbing;
• Sores.

 Registration
•

• Predisposition to epistaxis prior to the initiation of cancer-directed therapy (more than once a month over the previous year).
• Planned initiation or continuation of any topical nasal treatment other than the studied nasal spray,( such as nasal steroids, Ayr nasal gel, Neosporin ointment or nasal administration of petroleum jelly).  Taking Imitrex for migraines is acceptable.
• Previous exposure to rose geranium in sesame oil nasal spray.
• Concurrent upper respiratory tract infection.
• History of allergic or other adverse reactions to sesame oil or essential rose geranium oil.
• Any other reason that the study clinician or investigator feels precludes safe or appropriate inclusion in this study.

Re-Registration:

• The patient will be un-blinded and determined to have been on the saline arm, when initially randomized.

• Adult (≥18 years of age) donors recruited for lymphoid tissue biopsy by the principal investigator, co-investigators, study coordinators, Infectious Disease clinic nurses, or clinic phlebotomists.
• Required to have a platelet count >50,000/mm³ documented in the medical record within 30 days prior to the procedure.
• Eligible participants may have HIV infection, or another infection or inflammatory condition that may affect the content or structure of lymph nodes, or no known disease if used as a normal control. 

• Inability to provide informed consent
• Self-reported or clinically documented pregnancy
• Known allergy to local anesthetic
• Significant bleeding diatheses
• Active bacterial infection
• Any other condition that in the opinion of the principal investigator would increase the risk of the adverse events associated with the surgical procedure.

• Patient age is 18 years and older.
• Patient is willing and capable of providing written informed consent.
• Patients scheduled for a procedure who have clinical indication for ICE and in compliance with IFU.

• Patients in whom placement of an ICE catheter in the cardiac space or the vessel is contraindicated or technically not feasible.
• If femoral venous access is planned for ICE and IVC filter/IVC stent/iliac or femoral vein stent are present, an alternate access point should be used.

PRIOR TO STEP 1 REGISTRATION

• Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration.
• High-risk disease defined as having at least one or more of the following:
  • PSA > 20 ng/mL prior to starting ADT;
  • cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.]);
  • Gleason score of 8-10;
  • Node positive by conventional imaging with a short axis of at least 1.0 cm;
  • Appropriate stage for study entry based on the following diagnostic workup:
    • History/physical examination within 120 days prior to registration;
    • Bone imaging within 120 days prior to registration;
      • Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative Na F PET/CT or negative axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed).
  • Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or Na F PET will still be eligible.
  • CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only.
  • Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by > 10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e., N1), but whose nodes do not meet traditional size criteria for positivity (i.e., they measure ≤ 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration.
  • Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration).
  • Platelet count ≥ 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 120 days prior to registration).
  • Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration).
  • For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility.
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) within 120 days prior to registration.
    • Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject is eligible.
    • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (within 120 days prior to registration).
    • Serum albumin ≥ 3.0 g/dL (within 120 days prior to registration).
• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (didanosine [DDI] is not permitted) with undetectable viral load within 6 months are eligible for this trial and have a CD4 count ≥ 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to abiraterone acetate and apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with abiraterone acetate and apalutamide.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated.
  • Note: HBV viral testing is not required for eligibility for this protocol.
• 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.
  • Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator.
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

PRIOR TO STEP 2 RANDOMIZATION

• Confirmation of Decipher score.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 60 days prior. Note: Apalutamide may interfere with HCV drugs.
• Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol.

For patients entering the Intensification Cohort ONLY:

• Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization.

For patients entering the Intensification Cohort ONLY:

• Serum potassium ≥ 3.5 mmol/L prior to Step 2 randomization.

PRIOR TO STEP 1 REGISTRATION

• Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e., bone scan, CT scan, MRI).
• Prior systemic chemotherapy within ≤ 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration.
• Prior radical prostatectomy.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Current use of 5-alpha reductase inhibitor.
  • Note: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible.
• Didanosine (DDI) antiretroviral therapy is not permitted.
• History of any of the following:
  • Seizure disorder;
  • Current severe or unstable angina;
  • New York Heart Association Functional Classification III/IV;
    • Note: 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.
  • History of any condition that in the opinion of the investigator, would preclude participation in this study.
• Evidence of any of the following at registration:
  • Active uncontrolled infection requiring IV antibiotics;
  • Baseline moderate and severe hepatic impairment (Child-Pugh class B & C);
  • Inability to swallow oral pills;
  • Any current condition that in the opinion of the investigator, would preclude participation in this study.
• Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone [LHRH] agonist and oral anti-androgen) is ≤ 60 days prior to registration; Please note: baseline PSA and testosterone must be obtained prior to the start of any ADT.

PRIOR TO STEP 2 RANDOMIZATION

• Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration.

For patients entering the Intensification Cohort ONLY:

• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily.

For patients entering the Intensification Cohort ONLY:

• Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥ 160 mmHg or diastolic BP ≥ 100 mmHg);
• Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment.

• Ability to understand and provide written informed consent
• Age ≥ 50 years
• Current or Former Smoker
• ≥ 20 pack-years (pack years = number of packs per day X number of years smoked)

Inclusion Group 1: High Risk Patients that meet criteria 5 and 6 below:

• Prior thoracic imaging (computed tomography (CT)) within 12 months of enrollment OR Planned thoracic imaging (CT) as part of standard of care within 6 weeks of enrollment AND
• Meet one of the criteria below: a) No suspected or confirmed lung cancer diagnosis as defined by:
  • No clinical and/or radiological findings that indicate suspicion of lung cancer diagnosis (i.e., no lung nodules, <6mm lung nodules, ≥6mm lung nodules with no significant change from prior CT scan); OR
  • Suspected of lung cancer as defined by:
  • Radiological finding and/or clinical evaluation that indicates suspicion of lung cancer diagnosis (i.e., suspicious lung nodule(s) ≥6mm or Lung-RADS 3/4 for first-time CT scan patients and newly suspicious lung nodule(s) ≥ 6mm or Lung-RADS 3/4 identified within 6 months prior to enrollment for follow-up and surveillance CT scan patients). Subjects must have not received therapy prior to blood collection; OR
  • Confirmed, untreated lung cancer as defined by:
  • Pathologic diagnosis of lung cancer with no prior systemic therapy, definitive therapy, radiation, or surgical resection for any lesion.

Inclusion Group 2: High Risk Patients that meet the following criteria:

• Pathologic confirmed, invasive non-lung cancer diagnosis, originating from esophagus (upper), colon or rectum, pancreas, stomach (including lower esophagus), head and neck, bladder, kidney, or liver, with no prior systemic therapy, definitive therapy, radiation, or surgical resection; OR
• Clinically confirmed invasive non-lung cancer diagnosis originating from the pancreas, kidney, or liver, based on imaging and clinical judgement with planned treatment and no prior systemic therapy, definitive therapy, radiation, or surgical resection.

• Prior systemic therapy, definitive therapy, radiation, or surgical resection for cancer within one year prior to enrollment (with the exception of organ biopsies or surgery for non-melanoma skin cancer).
• Any history of hematologic malignancies or myelodysplasia.
• Any history of organ tissue transplantation.
• History of blood product transfusion within 120 days prior to enrollment.
• Current pregnancy.
• Any condition that in the opinion of the Investigator should preclude the subject’s participation in the study.
• Prior systemic therapy.
• Prior systemic therapy, definitive therapy, radiation, or surgical resection for the enrollment cancer diagnosis (with the exception of organ biopsies or surgery for non-melanoma skin cancer are not exclusionary).
• Enrollment in the DELFI-L201 study.

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

Eligibility last updated 12/15/23. Questions regarding updates should be directed to the study team contact.

• Current employees at Mayo Clinic who were transitioned from an in-person work environment to telework due to COVID-19 public health guidelines.

• Employees at Mayo Clinic who were not transitioned from an in-person work environment to telework due to COVID-19 public health guidelines.

Eligibility last updated 11/5/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 8/17/22. Questions regarding updates should be directed to the study team contact.

• Participants diagnosed with Atopic Dermatitis (AD) as defined by the Hanifin and Rajka criteria.
• Participants with AD duration of at least 3 months (participant/parent/guardian may verbally report signs and symptoms of AD with onset at least 3 months prior).
• Participants with IGA score of 2 to 3 at the screening and baseline visits.
• Participants with % BSA (excluding scalp) of AD involvement of 3% to 20% at screening and baseline visits.
• For children aged 6 years to < 12 years, baseline itch NRS score ≥ 4.
• Participants/guardians who agree to discontinue all agents used by the participant to treat AD from the screening visit through the final safety follow-up visit.
• Participants with at least 1 target lesion that measures at least 5 cm^2 at the screening and baseline visits. The target lesion must be representative of the participant's disease state but not located on the hands, feet, or genitalia.
• Willingness to avoid pregnancy or fathering a child for the duration of study participation.

• An unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator over the previous 4 weeks before the baseline visit. -Concurrent conditions and history of other diseases as follows:
  • Immunocompromised;
  • Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit;
  • Active acute bacterial, fungal, or viral skin infection within 1 week before the baseline visit;
  • Any other concomitant skin disorder, pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of AD lesions or compromise participant safety;
  • Presence of AD lesions only on the hands or feet without prior history of involvement of other classic areas of involvement such as the face or the flexural folds;
  • Other types of eczema;
  • Chronic asthma requiring more than 880 µg of inhaled budesonide or equivalent high dose of other inhaled corticosteroids.
• Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• Use of any of the following treatments within the indicated washout period before the baseline visit:
  • 5 half-lives or 12 weeks, whichever is longer – biologic agents (e.g., dupilumab);
  • 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogues, cyclosporin, methotrexate, azathioprine, or other systemic immuno-suppressive or immunomodulating agents (e.g., mycophenolate or tacrolimus);
  • 2 weeks – immunizations with live-attenuated vaccines; sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted).
  • Note: Live-attenuated vaccines are not recommended during the VC period. Note: COVID-19 vaccination is allowed;
  • 1 week – use of topical treatments for AD (other than bland emollients; e.g., Aveeno® creams, ointments, sprays, soap substitutes), such as topical antipruritics (e.g., doxepin cream), corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar (shampoo), topical antibiotics, or antibacterial cleansing body wash/soap.
  • Note: Diluted sodium hypochlorite "bleach" baths are allowed as long as they do not exceed 2 baths per week and their frequency remains the same throughout the study.
• Participants who have previously received JAK inhibitors, systemic or topical.
• Ultraviolet light therapy or prolonged exposure to natural or artificial sources of UV radiation (e.g., sunlight or tanning booth) within 2 weeks prior to the baseline visit and/or intention to have such exposure during the study, which is thought by the investigator to potentially impact the participant's AD.
• Positive serology test results at screening for HIV antibody.
• Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication or current enrollment in another investigational drug protocol.
• In the opinion of the investigator, unable or unlikely to comply with the administration schedule and study evaluations.
• Employees of the sponsor or investigator or otherwise dependents of them.

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

Inclusion Criteria:

• Patient with pathologically confirmed HCC not amenable to curative resection, transplantation or ablative therapies.
• Have radiographically measurable disease by RECIST.
• Eligible for atezolizumab/bevacizumab front line therapy.
• Male or female with age greater than 18 years, with the capacity and willingness to provide written informed consent.

• Pregnant and/or breast-feeding patients. A negative pregnancy test within 48 hours of the PET scan.
• Patients with higher than the weight/size limitations of PET/CT scanner.

Inclusion Criteria

• Willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally authorized representative must provide informed consent on his/her behalf.
• Males or females ≥ 18 years of age.
• Evidence of candidemia or invasive candidiasis based on growth of Candida species from any of the following: blood, peritoneal fluid, intra-abdominal collection/abscess, pancreatic fluid/tissue, peripancreatic fluid, pleural fluid/tissue.

• Severe neutropenia (absolute neutrophil count < 500 cells/microL).
• Profound lymphopenia (< 300 cells/microL).
• The Principal Investigator (PI) is of the opinion that the subject should not participate in the study.

Eligibility last updated 8/23/21. Questions regarding updates should be directed to the study team contact.

• Patients with clinical and imaging evidence of middle ear cholesteatoma.

• Any patients who would be unable to undergo MR (claustrophobia, implanted device, etc.).

• Diagnosis of rheumatoid arthritis defined by ACR/EULAR criteria.
• Diagnosis of immune-mediated disease affecting the joint, the lung, the muscle, the nervous system, the heart, or the vascular system. Diagnosis will be made by a qualified rheumatologist.

• Chronic viral infection.
• History of chemo/radiotherapy.
• History of cancer.
• Healthy Controls:
  • Personal or family history of autoimmune disease;
  • Personal history of chemo/radiotherapy;
  • Personal history of cancer (with the exception of basal cell carcinoma of the skin);
  • Personal or family history of immunodeficiency.

• Has a diagnosis of juvenile or adolescent idiopathic scoliosis.
• Is skeletally immature with a Sanders Score of ≥ 2 to ≤ 5.
• Has failed conservative care as per investigator’s assessment.
• Has a main thoracic Cobb angle between 30 and 60 degrees.
• Has a Lenke Classification of 1A, 1B, or 1C.
• Has kyphosis ≤ 40 degrees with a sagittal thoracic modifier N or negative.
• Informed Consent Form/Assent and Authorization to Use and Disclose Health Information (if applicable) have been signed by parent/legal guardian and/or patient/participant per local requirement.

• Has undergone previous spinal fusion procedure(s) at the affected levels.
• Is pregnant or plans to become pregnant within the first 24‐months of the study.
• Has a curve that requires instrumentation below L1.
• Has spinal MRI abnormalities (e.g., CHIARI malformation, Syrinx greater than 4mm, tethered cord).
• Has any type of non‐idiopathic scoliosis.
• Has a left‐sided curve.
• Has an associated syndrome.
• Has a history of malignant hyperthermia.
• Has an active or significant risk of infection (immunocompromised).
• Has inadequate tissue coverage over the operative site as per investigator’s assessment.
• Has a suspected or documented allergy or intolerance to implant materials.
• Has a major psychiatric disorder/ history of drug abuse that would interfere with the subject’s ability to comply with study instructions or might confound the study interpretation as per investigator’s assessment (DSM‐5 can be used as a reference).
• Is a ward of the court/state.
• Has had prior ipsilateral or contralateral chest surgery.
• Has severe chronic lung disease (e.g., asthma, bronchiectasis).
• Has poor bone quality, as determined by the investigator, that may limit anterior fixation.
• Is unwilling or unable to return for follow‐up visits and/or follow intra‐operative and/or postoperative instructions.
• Concurrent participation in another clinical study that may add additional safety risks and/or confound study results*.
• Subjects in concurrent studies can only be enrolled with permission from Medtronic. Please contact Medtronic’s study manager to determine if the subject can be enrolled in the BRAIVE IDE Study.

*Subjects in concurrent studies can only be enrolled with permission from Medtronic. Please contact Medtronic’s study manager to determine if the subject can be enrolled in the BRAIVE IDE Study. 

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

• Patient must be ≥ 18 years of age.
• Patient must have histologically confirmed adenocarcinoma of the rectum with the inferior margin within 15 cm from the anal verge based on colonoscopy and/or flexible sigmoidoscopy.
• Patient must have T3-4Nx or TxN+ disease (stage II or III) based on magnetic resonance imaging of the pelvis and computed tomography of the chest and abdomen. These baseline scans must be done within 28 days prior to registration.
• Patient must have MSI-H (microsatellite instability-high) or dMMR (deficient mismatch repair) tumors based on immunohistochemistry or PCR (polymerase chain reaction).
• Patient must have Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
• 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 agree to not receive live vaccines while on this study.
• 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 for at least one month (female patients) or one week (male patients) prior to the start of study drug and continue for 5 months after the last dose of study drug (for female patients). Investigators must counsel patients on the importance of pregnancy prevention and the implications of an unexpected pregnancy.
• Leukocytes ≥ 3,000/mcL (must be obtained ≤ 14 days prior to protocol registration).
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (must be obtained ≤ 14 days prior to protocol registration).
• Platelets ≥ 100,000/mcL (must be obtained ≤ 14 days prior to protocol registration).
• Total bilirubin ≤ institutional upper limit of normal (ULN) (must be obtained ≤ 14 days prior to protocol registration).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x institutional ULN (must be obtained ≤ 14 days prior to protocol registration)
• Creatinine ≤ 1.5 x institutional ULN (must be obtained ≤ 14 days prior to protocol registration).
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• 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 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 not have previously received chemotherapy or immunotherapy for rectal cancer.
• Patient must not have previously received radiotherapy to the pelvis.
• Patient must not have had major surgery performed within 28 days prior to registration.
• Patient must not have a history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan.
• Patient must not have a serious active infection requiring IV antibiotics at time of registration.
• Patient must not have active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater). These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or anti-phospholipid syndrome. Patients with any of these are ineligible for this study because of the risk of recurrence or exacerbation of disease.
• Patient must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Patient 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 2 weeks prior to registration to rule out pregnancy. A repeat pregnancy test must be done within 72 hours prior to first dose of treatment if the baseline test was done outside the 72 hour window. A patient of childbearing potential is defined as anyone, 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).

Eligibility last updated 9/14/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 8/24/22. Questions regarding updates should be directed to the study team contact.

Registration
•Inclusion Criteria

• Age ≥ 18 years.
• Diagnosed with cancer and receiving chemotherapy.
• Able to provide informed consent.
• Willingness to complete questionnaires.
• ECOG Performance Status (PS) 0, 1, 2.
• One or more of the following nasal symptoms for which the patient reports they would appreciate treatment. Symptoms must have started after the initiation of systemic, antineoplastic therapies, be attributed to the systemic, antineoplastic therapies, and symptoms must be reported  as being moderate (corresponding to a score of 2) or worse on a scale from mild (1) to very severe (4) on at least one of the items below.
• Dryness;
• Discomfort/Pain;
• Bleeding;
• Scabbing;
• Sores.

 Registration
•

• Predisposition to epistaxis prior to the initiation of cancer-directed therapy (more than once a month over the previous year).
• Planned initiation or continuation of any topical nasal treatment other than the studied nasal spray,( such as nasal steroids, Ayr nasal gel, Neosporin ointment or nasal administration of petroleum jelly).  Taking Imitrex for migraines is acceptable.
• Previous exposure to rose geranium in sesame oil nasal spray.
• Concurrent upper respiratory tract infection.
• History of allergic or other adverse reactions to sesame oil or essential rose geranium oil.
• Any other reason that the study clinician or investigator feels precludes safe or appropriate inclusion in this study.

Re-Registration:

• The patient will be un-blinded and determined to have been on the saline arm, when initially randomized.

Subjects who meet all the following criteria will be eligible for the study:

• Women and men between 18 and 85 years of age.
• Have a diagnosis of interstitial lung disease (ILD) according to the American Thoracic Society Guidelines.
• Have a chronic cough for at least 3 months prior to the screening visit.
• Patients should be on a stable dose of ILD-directed therapies for 3 months prior to enrollment and will be allowed to continue their ILD-directed therapies. These include –but are not limited to- corticosteroids, immunosuppressing agents such as azathioprine and mycophenolate, as well as antifibrotic medications including nintedanib and pirfenidone. Additional corticosteroids and adjustment of ILD-directed therapy doses is permitted if deemed appropriate by the treating physician.
• Have a score of ≥ 40mm on the Cough Severity VAS at Screening..
• Women of child-bearing potential must use 2 forms of acceptable birth control and make no donation of eggs from Screening through the end of the 8-week study period. Acceptable birth control methods include established use of oral, injected, or implanted hormonal methods of contraception; intrauterine device (IUD) or intrauterine system (IUS); tubal ligation; or male sterilization. Double-barrier method (diaphragm for female subject and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control. When concordant with the preferred lifestyle of the subject, true and complete abstinence (not periodic abstinence) is acceptable.
• Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control, 1 of which must be a barrier method, and make no donation of sperm from Screening until 3 months after the last dose of study drug at the end of 8 weeks.
• Have provided written informed consent.
• Are willing and able to comply with all aspects of the protocol.

Subjects are NOT eligible for this study if they meet any of the following criteria:

• Current smoker (cigarettes, e-cigarettes or marijuana) or former smokers who have smoked within the past 12 months.
• Former smokers with > 20 pack-year history of smoking.
• Ongoing treatment with an ACE-inhibitor that is considered as the potential cause of a subject’s cough or requiring treatment with an ACE-inhibitor during the study or within 12 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).
• History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Screening/Baseline Visit (Day -14 to Day 0).
• History of opioid use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0). Use of opioids for other indications (for example, to treat pain) is permitted.
• History of baclofen use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0). Use of baclofen for other indications (for example, to treat spasticity) is permitted.
• Presence of an untreated or undertreated cause (other than ILD) for the patient’s chronic cough (per ACCP guidelines). e.g. uncontrolled asthma, GERD or post-nasal drainage that could potentially explain the patient’s chronic cough.
• Requiring concomitant therapy with prohibited medications.
• Treatment with any pharmaceutical or biological investigational therapy (excluding COVID vaccination and COVID related monoclonal antibody therapy).
• Participation in another clinical trial that does not allow co-enrollment within 4 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).
• Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x the upper limit of normal (ULN) during screening.
• Serum creatinine < 30 mL/min, hemodialysis or peritoneal dialysis.
• Advanced liver disease as defined by the presence of cirrhosis and/or signs of portal hypertension.
• History of previous hypersensitivity or intolerance to Duloxetine & Amitriptyline (patients who have previously been on either amitriptyline or duloxetine for chronic cough or other reasons and have tolerated the medication will be offered participation regardless of previous response to therapy).
• Currently pregnant or breastfeeding female subject.
• Presence of any medical condition or disability that the investigators believe could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject.
• Planned or anticipated major surgical procedure or other activity that would interfere with the subject’s ability to comply with protocol-mandated assessments (e.g., extended travel) during the subject’s participation in the study. 
• Currently taking either another SSRI, SNRI or MAO inhibitor which the patient cannot safely discontinue at least 2 weeks prior to the screening period.

Eligibility last updated 6/3/22. Questions regarding updates should be directed to the study team contact.

• 18 years or older.
• Undergoing EBUS procedure for diagnosis or staging of lung diseases.

• Under 18 years old.

Eligibility last updated 10/6/21. Questions regarding updates should be directed to the study team contact.

• Current admission is the child’s first PICU admission.
• Patient age ≥ 4 weeks and ≥ 44 weeks corrected gestational age, and < 16 years (has not yet reached 16th birthday) on PICU admission.
• At least one parent/legal guardian (≥ 18 years of age or considered emancipated) living with the potential subject.
• PICU LOS of ≥ 3 days (covering at least 3 nights from midnight to 7am) in which the patient received intensive care therapies for organ dysfunction (invasive mechanical ventilation, vasopressors/inotropes, acute renal replacement therapy, or other extracorporeal therapies).
• Anticipated patient discharge to home (direct or indirect).

• Patient history of neonatal intensive care unit hospitalization.
• Life expectancy not anticipated to be more than one year (e.g., active do not resuscitate [DNR] plan or actively managed by the palliative care team for end-of-life symptom management).
• Patient in foster care or ward of the state.

Eligibility last updated 10/18/21. Questions regarding updates should be directed to the study team contact.

• Patient must have locally advanced unresectable stage IIIC or stage IV melanoma.
• Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay.
• Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Baseline measurements of sites of disease must be obtained within 3 weeks prior to study randomization.
• Patient must have been treated with prior immune checkpoint inhibitor therapy (anti PD-1 antibody, anti-CTLA-4 antibody or a combination regimen including either or both agents) either in the adjuvant or metastatic setting.
• Patient may have received investigational agents in combination with standard therapy, as long as it was adhering to the timeframes.
• Patient must have discontinued active immunotherapy (IL-2, interferon, anti-CTLA-4 antibody, anti-PD-1 antibody etc.) or chemotherapy at least 4 weeks prior to randomization.
• Patient must have discontinued any oral targeted therapy at least 2 weeks prior to randomization.
• Patients must not receive any other investigational anticancer therapy during the period on study or the 4 weeks prior to randomization.
• Patient may have been treated with prior adjuvant therapy including combined BRAF and MEK inhibitor therapy. Patients will be eligible if they tolerated this therapy and did not discontinue the therapy due to toxicity AND ≥ 6 months have elapsed since the end of adjuvant BRAF and MEK inhibition. If patients received BRAF and MEK inhibitor therapy in the metastatic setting, they are not eligible.
• Patient may have been treated with prior chemotherapy or radiation therapy.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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
• Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse for the duration of their participation in the study and for 4 months after the last dose of protocol treatment.
• Patient must have recovered from clinically significant reversible toxicities from previous treatment prior to randomization. Abnormal laboratory values may be grade 1, as long as they meet the eligibility criteria.
• Patient must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• 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
• Absolute neutrophil count ≥ 1,500/mcL (obtained ≤ 14 days prior to protocol randomization).
• Platelets ≥ 100,000/mcL (obtained ≤ 14 days prior to protocol randomization).
• Total bilirubin ≤ institutional upper limit of normal (ULN) (obtained ≤ 14 days prior to protocol randomization).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3.0 x institutional ULN (obtained ≤ 14 days prior to protocol randomization).
• Creatinine ≤ 1.5 x institutional ULN (obtained ≤ 14 days prior to protocol randomization).
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patient with asymptomatic new or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that CNS specific treatment is not required.
  • NOTE: Patient with treated brain metastases are eligible. No brain imaging is required, however, 1 week must elapse after gamma knife therapy. Patient treated with whole brain radiation that have been stable for 2 months are eligible. Patient are excluded if they have leptomeningeal disease or metastases causing spinal cord compression that are symptomatic or untreated or not stable (documented by imaging) for at least 3 months or requiring corticosteroids.
• Patients on a stable dose of corticosteroids for at least 1 month or who have been off of corticosteroids for at least 1 week are eligible.

• Patients who are known to be experiencing an objective partial response to immunotherapy at the time of study enrollment are not eligible.
• Women 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 females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is defined as any woman, 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).
• Patient must not have a history of interstitial lung disease (ILD) or chronic pneumonitis.
  • NOTE: If there is radiographic evidence of ILD that is clinically insignificant and asymptomatic, the patient would be eligible.
• Patient must not have porphyria or psoriasis due to risk of disease exacerbation unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations.
• Patient must not have a previously documented retinal vein occlusion.
• Patient must not have a history or evidence of increased cardiovascular risk including:
  • Left ventricular ejection fraction (LVEF) < institutional lower limit of normal measured within 14 days prior to randomization;
  • A QT interval corrected for heart rate using the Bazett's formula ≥ 480 msec;
  • Current clinically significant uncontrolled arrhythmias.
  • Exception: Patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible;
  • Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization;
  • Abnormal cardiac valve morphology (≥ grade 2) documented by echocardiogram unless a cardiologist concludes the valve abnormality is not clinically significant. Patients with grade 1 abnormalities (i.e., mild regurgitation/stenosis) are eligible;
  • 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 with known serious concurrent infection or medical illness, including psychiatric disorders, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety are not eligible.
• Patient must not be receiving concurrent therapy for their tumor (i.e., chemotherapeutics or investigational agents). Radiotherapy delivered to palliate pain is allowed as long as it is not targeting a lesion that meets RECIST criteria for progression. Radiation therapy to the surgical bed with gamma knife radiotherapy while on treatment during the first cycle is allowed for small volume surgically resected brain metastases. Gamma knife radiotherapy for known active, asymptomatic small volume central nervous system (CNS) lesions may be performed during the first cycle while on study. Radiotherapy for new CNS lesions identified beyond the first cycle is not allowed on study.
• Patient must not have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
• Patient must not have received cytochrome P450 enzyme-inducing anticonvulsant drugs (extended-interval aminoglycoside dosing [EIADs]) (i.e., phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) within 4 weeks prior to randomization.
• Patient must not have a current use of a prohibited medication.

• Children aged 14 days
  •17 years.
• At least moderate PARDS, bilateral lung disease, intubated within four days of severe PARDS and no exclusion criteria.

• Children will be excluded if they have any of the following at the start of mechanical ventilation: perinatal related lung disease, congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis, respiratory failure explained by cardiac failure or fluid overload, cyanotic heart disease, cardiomyopathy, unilateral lung disease, primary pulmonary hypertension, status asthmaticus (patient with a severe asthma exacerbation. A previous history of asthma or the use of bronchodilators is NOT an exclusion if the primary disease process is not considered to be obstructive airway disease), obstructive airway disease (e.g., severe airways disease without parenchymal involvement or disease characterized by hypercapnia with FiO2 < 0.30 and/or evidence of increased resistance visible on the flow – time scalar and/or presence of intrinsic PEEP),  bronchiolitis obliterans, post Hematopoietic Stem Cell Transplant, post lung transplant, home ventilator (including noninvasive) dependent, neuromuscular respiratory failure, critical airway (e.g., post laryngotracheal surgery or new tracheostomy) or anatomical obstruction of the lower airway (e.g., mediastinal mass), facial surgery or trauma in previous 15 days, head trauma, intracranial bleeding, unstable spine, femur or pelvic fractures, acute abdominal process/open abdomen, supported on ECMO, previously enrolled in current study, family/medical team deciding not to provide full support, enrolled in any other critical care interventional clinical trial concurrently and known pregnancy.

Eligibility last updated 10/7/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

• Ability to provide informed consent.
  • Pediatric patients must provide assent in addition to their parents’/guardians’ consent.
• Age ≥ 12 years.
• Vestibular schwannoma categorized by * AND **

* NF2-associated OR sporadic

** Newly diagnosed within the last two years OR growing (tumor will be considered growing if it has shown ≥ 2mm increase in any dimension between scans at least 6 months apart).

• Confirmed radiographic diagnosis of vestibular schwannoma by an MRI scan with contrast. Image must be present at baseline.
• Ability to swallow capsules.

• Use of aspirin (or aspirin containing products) more than four times in a single week within the last two months is exclusionary. However, patients may be eligible if they complete a 60-day washout period from aspirin.
• Use of systemic steroids or non-steroidal anti-inflammatory drugs (NSAIDs more than four times in a single week in the last two months is exclusionary.  Patients may be eligible if they complete a 60-day washout period from NSAIDs and steroids.
• Refusal to refrain from the use of aspirin, aspirin containing products, NSAIDs, and steroids throughout the course of the study  Refer to Appendix IV “Common Medications Containing Aspirin” below.
• Chronic anticoagulation with agents such as Coumadin, Pradaxa, Xarelto, Apixaban, Eliquis, Plavix, Angiomax, Argatroban, Iprivask, Heparin, Lovenox, Fragmin, Innohep, Fraxiparine, Arixtra, etc.
• Prior treatment for vestibular schwannoma as follows:
  • Radiation to target lesion. For patients with bilateral vestibular schwannomas of which only one has been irradiated, patients will be eligible if the tumor on the non-irradiated side is designated the target lesion;
  • Avastin  (bevacizumab) within 60 days prior to enrollment. Patients who have more than 60 day washout period are eligible;
  • Surgical resection of target lesion within 6 months prior to enrollment. Patients with prior surgical resection of the target lesion must have a post-op scan that shows residual tumor in order to be eligible. For patients with bilateral vestibular schwannomas of which only one has been resected, patients will be eligible if the tumor on the non-resected side is designated the target lesion.
• Known allergy to aspirin.
• Impairment of gastrointestinal function or gastrointestinal disease present in the medical history or reported by patient that may significantly alter the absorption of aspirin.
• In the opinion of the investigator, the patient is at an increased risk of gastrointestinal bleeding, for any reason.
• Pregnant or lactating women.
• Patients with serious medical illnesses (e.g. severe asthma) that in the option of the investigator could prevent participation in the trial.
• Active bleeding diathesis.
• Hydrocephalus from brainstem compression.
• History of febrile or flu-like illness in children and adolescents less than 18 years of age when taking aspirin.

Eligibility last updated 3/1/22. Questions regarding updates should be directed to the study team contact.

• Female patients age 18 at the time of signing informed consent, up to 55 years of age.
• Ultrasound confirmation of twin pregnancy no later than 20 weeks gestational age (GA), and prior to Panorama.
• Panorama planned no later than 20 weeks GA.
• Willing and able to provide written informed consent.
• Willing and able to comply with institution’s standard of care prenatal procedures, including ultrasound assessments and Panorama.
  • Note: subjects with known major congenital anomalies, known unbalanced chromosomal complement or ruptured membranes, may be enrolled in the study.

• Singleton or non-twin multiple pregnancy.
• Ultrasound confirmation of twin pregnancy at 20 weeks 1 day GA or later.
• Patient has received a Panorama test and the enrolling physician has received the Panorama test results prior to any ultrasound assessment of chorionicity & amnionicity.
• Panorama testing is planned at 20 weeks 1 day GA or later.
• Any confounding complication or condition that, in the opinion of the investigators, precludes participation in the study, such as evidence of TTTS or other monochorionic pregnancy complication already at the time of enrollment.
• Unwilling or unable to participate in the institution’s standard of care prenatal ultrasound and/or testing with Panorama.
• Unwilling or unable to provide written informed consent.

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

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

Eligibility last updated 5/31/23. Questions regarding updates should be directed to the study team contact.

• Histologically confirmed diagnosis of medulloblastoma.
• SHH, Group 3, or Group 4 according to World Health Organization 2016 classification.
• Recurrent or refractory to frontline therapy, defined as:
  • For Part 1 only: Recurrent (maximum of 2 recurrences) or refractory to frontline therapy. Prior frontline or second-line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent chemotherapy regimens.
  • For Part 2 only: Recurrent (maximum of 1 recurrence) or refractory to frontline therapy. Patients with recurrent disease must have received second-line chemotherapy for progressive disease. Prior frontline or second-line therapy may involve surgery, craniospinal irradiation, stereotactic radiosurgery, and multi-agent chemotherapy regimens.
• Have refractory disease, focal or multifocal recurrent disease, or pure leptomeningeal disease. Cytological or radiographic remission is allowed; however, not simultaneously.
• Performance status score of 50 to 100, both inclusive, on the Lansky [<16 years] or Karnofsky [≥16 years] scales.
• Aged 3 to 19 years, both inclusive, at the time of the first planned dose of trial treatment.
• Life expectancy of at least 3 months, as judged by the Investigator.
• Acceptable hematological status and liver and kidney function.

• Obstructive or symptomatic communicating hydrocephalus as determined by Ommaya patency/cerebrospinal fluid (CSF) flow study.
• Any tumor lesion measuring >15 mm in the smallest diameter
• Ventriculoperitoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts.
• Grade 4 nervous system disorder. Stable neurological deficits due to brain tumor or surgery and hearing loss are allowed.
• Uncontrolled life-threatening infection.
• Received radiation therapy (focal or cranio-spinal irradiation), systemic or intrathecal cytotoxic chemotherapy, or intrathecal immunotherapy (corticosteroids not included) less than 3 weeks prior to the Screening Visit. Received nitrosoureas less than 6 weeks or monoclonal antibodies less than 5 half-lives prior to the Screening Visit.
• Received systemic or intrathecal cytotoxic chemotherapy or intrathecal immunotherapy (corticosteroids not included) less than 3 weeks prior to the screening visit.
• Received any prior anti-B7-H3 treatment.
• Non-hematologic organ toxicity Grade 3 or above; specifically, any renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity.
• Females of childbearing potential, who are pregnant, breast feeding, intend to become pregnant, or are not using highly effective contraceptive methods or males who are not using highly effective contraceptive methods.

• Male or female age ≥ 22 years and < 80 years.
• Clinical decision to proceed with AF ablation procedure.
• Ablation procedure to be completed with General Anesthesia.
• Ablation procedure to be completed with use of radiofrequency catheter ablation.

• History of various esophageal pathology such as esophageal achalasia, varices, strictures, web, carcinoma, tumor/mass, scleroderma, Mallory-Weiss tear, Barrett's esophagitis, diverticulum, banding, laceration, perforation, balloon dilatation.
• Presence of a pH probe deployed in the esophagus.
• Planned AF ablation procedure to be completed with laser energy or with cryo-energy.
• Acute or uncontrolled psychiatric illness.
• Unable to undergo upper endoscopy.
• Enrollment in another FDA clinical trial.
• Unstable medical condition(s) that precludes safely completing study protocol.
• Subject is incarcerated.
• Subject is pregnant.
• Subject is unable to comprehend the details of the study.
• The Investigator believes that the subject will be unwilling or unable to comply with study protocol requirements, including the investigational device procedure and study-related follow up visit requirements.

• Patients ≥ 18 to ≤ 80 years (at date of signing the informed consent form [ICF]), but at least of legal age in the given country.
• Biopsy confirmed diagnosis of IgAN within the past 8 years prior to signature of the ICF.
• Proteinuria at screening visit ≥ 1.0 g/d.
• Treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) at maximum doses or maximally tolerated doses for ≥ 3 months prior to date of informed consent and adequate blood pressure (BP) control (recommended BP is < 125 mm Hg systolic and < 75 mm Hg diastolic) In case a patient is intolerant to even a very low dose of either ACEi or ARB therapy, approval for participation in the trial has to be obtained from the Medical Monitor prior to randomization.
• A female of childbearing potential (FCBP) is only eligible to participate if she is not pregnant, not breast feeding, and agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of Felzartamab.

• Secondary forms of IgAN, indicated by the presence of any other systemic disease potentially leading to IgA deposits (e.g., Lupus nephritis, Schönlein-Henoch purpura, ankylosing spondylitis, dermatitis herpetiformis, chronic liver disease, inflammatory bowel disease, celiac disease).
• Severe renal impairment as defined by estimated GFR < 30 mL/min (using chronic kidney disease-epidemiology collaboration [CKD-EPI] formula) or the need for dialysis or renal transplant.
• Rapidly progressive variant of IgAN, defined as eGFR loss by more than 30% per 3 months and not explained by changes in renin angiotensin system (RAS) blockade.
• Minimal change variant of IgAN.
• Concomitant other progressive glomerulonephritis or non-immunologic glomerular disease such as diabetic nephropathy.
• Systemic immunosuppression (e.g. mycophenolate mofetil [MMF], cyclophosphamide, biologics like rituximab [RTX]), in particular corticosteroid therapy exceeding 20 mg/day prednisone-equivalent for more than 7 consecutive days within 180 days prior to signing ICF.
• Any previous treatment with an anti-CD38 antibody.
• Body mass index (BMI) > 35 kg/m^2.
• Hemoglobin < 90 g/L.
• Thrombocytopenia: Platelets < 100.0 x 10^9 /L.
• Neutropenia: Neutrophils < 1.5 x 10^9 /L.
• Leukopenia: Leukocytes < 3.0 x 10^9 /L.
• Diabetes mellitus type 1.
• Diabetes mellitus type 2:
  • Patients with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to signing ICF shows IgAN without evidence of diabetic nephropathy and their disease is controlled, such as:
    • Glycated hemoglobin (HbA1c) < 8.0% or < 64 mmoL/mol.;
    • No diabetic retinopathy known;
    • No peripheral neuropathy known.
• Significant uncontrolled cardiovascular disease (including arterial or venous thrombotic or embolic events) or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
• Clinically significant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening.
• History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity ≥ grade 3.
• Aspartate aminotransferase or alanine aminotransferase > 1.5 x ULN, alkaline phosphatase > 3.0 x ULN.
• Known or suspected hypersensitivity to Felzartamab and its excipients (L-histidine, sucrose, polysorbate 20).
• Serologic markers positive for HIV or history of HIV, hepatitis C (patients with positive anti-hepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] can enroll) or active or latent hepatitis B (patients with positive hepatitis B surface antigen [HBsAg] are excluded). For patients with positive hepatitis B core antibody [anti-HBc], hepatitis B virus (HBV) DNA test by PCR must be non-detectable to enroll).
• Any malignancy within 5 years prior to screening start, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or other non-melanomatous skin cancer.
• Treatment within 5 terminal half-lives (if known) or within the last 30 days prior to Visit 2, whatever is longer) with investigational drugs.
• Any active infection (viral, fungal, bacterial) requiring systemic therapy.

Eligibility last updated 1/19/22. Questions regarding updates should be directed to the study team contact.

• Adults (≥ 18 years of age) with established enteral access, currently enrolled in Mayo Clinic HEN program.
• Established enteral access.
• Anticipated to require enteral nutrition (EN) to provide 90% or more of their nutritional needs for at least 14 days.
• Having obtained their or their legal representative’s signed informed consent.

• Individuals under 18 years if age,
• Condition which contraindicates enteral feeding (i.e., intestinal obstruction).
• Any condition that would contraindicate use of the study product (i.e., need for severe fluid restriction, cow’s milk protein allergy, fish allergy, other).
• Patients with active colitis, radiation enteritis, short bowel syndrome, undergoing active cancer treatment.
• Judged to be at risk for poor compliance to the study protocol.
• Currently participating in a conflicting clinical trial.