Key

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

Eligibility last updated 7/11/23. Questions regarding updates should be directed to the study team contact.

• Male or female, age above or equal to 18 years at the time of signing informed consent.
• Body mass index (BMI) greater than or equal to 30.0 kg/m^2.
• New York Heart Association (NYHA) Class II-IV.
• Left ventricular ejection fraction (LVEF) greater than or equal to 45% at screening -Diagnosed with T2D greater than or equal to 90 days prior to the day of screening.
• HbA1c of below or equal to 10.0% as measured at the screening visit.

• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Eligibility last updated 9/7/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 6/15/22.  Questions regarding updates should be directed to the study team contact.

• Understand and voluntarily sign an informed consent form.
• Patients must be at least 22 years of age.
• Patients must be able to undergo routine non-contrast CT scans of the chest.
• Patient must be stable for general anesthesia and have an airway amenable to rigid bronchoscopy and stent implantation.
• The patients must have at least an expected 6 month survival.
• Patient must be able to maintain standard of care follow-up schedule and have access to standard of care medications and nebulizer machines and/or suction and oxygen as required for primary disease management.
• Patient must be able to personally provide consent and be able to describe Dyspnea and QOL and other patient-reported outcomes (PROs) required by study design.
• Patient must require a stent that is within the design envelope of the patient-specific stents, as defined by COS.

• Patients may be excluded if the disease can be managed by simply removing prior stents or performing more conservative therapies.
• Chronic anticoagulant therapy that could limit the safety of performing rigid therapeutic bronchoscopy in a timely manner. (I.e. Plavix within one year of drug eluding cardiac stent (DES) or 6 weeks following bare metal coronary stent).
• Unstable cardiac disease.
• Allergy to silicone.
• Stenting to manage vascular compression syndromes.
• Multi-drug resistant bacterial or fungal chronic infections.
• Emergent/urgent clinically indicated stent.
• Chronic/permanent mechanical ventilation.
• Pure Excessive Dynamic Airway Collapse (EDAC) patients.
• Pure Pulmonary Resistance (Rp) patients.

Eligibility last updated 11/4/21. Questions regarding updates should be directed to the study team contact.

• Evaluation for total knee arthroplasty (TKA) at Mayo Clinic (Rochester, MN) or OrthoCarolina (Charlotte, NC).
• Evaluated and scheduled for TKA at Mayo Clinic by Drs. Cody Wyles, Robert Trousdale, Kevin Perry, Corey Couch, or Nic Bedard or at OrthoCarolina by Drs. Thomas Fehring, Bo Mason, Keith Fehring, or Jesse Otero. 
• Determined by the above surgeon to be a candidate for the Attune Posterior Stabilized knee system, with the patella to be resurfaced during surgery.
• ≥ 18 years of age at enrollment.

• Previous surgery with hardware on the joint of interest.
• Varus or valgus defor 1mity > 15° or any other preoperative deformity at the discretion of the surgeon portending a risk of needing a constrained or hinged device.
• Previous diagnosis of inflammatory disease (RA, inflammatory arthropathy, any autoimmune disease).
• BMI ≥ 40.
• Physician discretion due to not being able to follow standard-of-care (SOC) TKA follow up protocol.
• Contralateral side previously enrolled in this study (i.e., simultaneous bilateral or staged bilateral patients cannot have both sides enrolled).
• Current tobacco use.

Eligibility last updated 11/17/21. Questions regarding updates should be directed to the study team contact.

• Histologically confirmed DLBCL or associated subtype, defined by WHO 2016 classification:
  • DLBCL not otherwise specified (NOS);
  • High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements;
  • High-grade B cell lymphoma, NOS o Primary mediastinal (thymic) large B cell lymphoma;
  • Transformed lymphoma (e.g., transformed follicular or marginal zone lymphoma, follicular lymphoma Grade 3).
• Relapsed or refractory disease after 2 or more lines of chemotherapy including rituximab and anthracycline and either having failed autologous stem cell transplant (ASCT), or being ineligible for or not consenting to ASCT 2.1.
• Chemotherapy-refractory disease is defined as one of the following:
  • No response to last line of therapy:
  • Progressive disease (PD) as best response to most recent therapy regimen o Stable disease (SD) as best response to most recent therapy with duration no longer than 6 months from last dose of therapy; OR
  • Relapsed or persistent disease after prior ASCT for lymphoma;
    • Disease progression or relapse less than or equal to 12 months of ASCT;
    • If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.
• Disease relapse in subjects without prior ASCT is defined as relapse of disease in ≤ 12 month after the last dose of most recent therapy regimen.
• Ineligible for ASCT is defined as meeting one of the following criteria:
  • Chemotherapy-refractory disease after salvage therapy;
  • Disease progression or relapse ≤ 12 months after salvage therapy;
  • Intolerance to salvage therapy.
• In addition, all subjects must have:
  • Age ≥ 18 years;
  • Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to DLBCL;
  • Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma (Cheson et al, 2014);
  • CD19 or CD20 antigen expression on tumor is not required after the most recent chemoimmunotherapy; however:
    • Subject must have at least 10 unstained slides of tissue available prior to MB-CART2019.1 infusion;
    • If archival tissue is not available, subject must be willing to undergo attempted repeat biopsy.
  • No clinical suspicion of central nervous system (CNS) lymphoma.
• If the subject has history of CNS disease, then he/she must:
  • Have no signs or symptoms of CNS disease;
  • Have no active disease on magnetic resonance imaging (MRI);
  • Have no large cell lymphoma present in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells (WBCs).
• If has history of cerebral vascular accident (CVA):
  • The CVA event must be greater than 12 months prior to leukapheresis;
  • Any neurological deficits must be stable.
• A creatinine clearance (as estimated by direct urine collection) > 60mL/min.
• Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA).
• Resting O2 saturation > 90% on room air.
• Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) 1000/μL.
• Absolute lymphocyte count > 100/μL.
• Platelet count > 50,000/µL.
• Estimated life expectancy of more than 3 months other than primary disease.
• Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study.

• Primary CNS lymphoma.
• Richter’s transformed DLBCL arising from chronic lymphocytic leukemia (CLL).
• Unable to give informed consent.
• Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive), unless confirmed to be polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive.
• Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing
• Known history of active seizure or presence of seizure activities or on active anti-seizure medications within the prior 12 months.
• Known history of CVA within prior 12 months.
• Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease.
• Presence of active CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity.
• Active systemic fungal, viral or bacterial infection.
• Pregnant or breast-feeding woman.
• Previous or concurrent malignancy with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry);
  • In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study;
  • Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years;
  • A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years.
• History of non-neurologic autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus) requiring systemic immunosuppressive or systemic disease modifying agents within the last 2 years.
• Medical condition requiring prolonged use of systemic corticosteroids equivalent to Prednisone > 10 mg/day.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.
• Concurrent radiotherapy (allow up to time of leukapheresis).
• Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Refusal to participate in additional lentiviral gene therapy long-term follow-up (LTFU) protocol.
• Prior CAR-T therapy for any indication.
• Prior allogeneic stem cell transplant for any indication.
• Prior Bispecific T cell engaging (BITE) antibodies for cancer therapy.
• Prior T cell receptor-engineered T cell therapy.

Key

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

Eligibility last updated 4/18/23. Questions regarding updates should be directed to the study team contact.

Screening

• The participant must be at least 18 years of age at the time of informed consent.
• The participant must provide written informed consent prior to any study procedures.
• The participant must meet diagnostic criteria for Gorlin Syndrome (GS) including major criterion #3a plus 1 additional major criterion or plus 2 additional minor criteria listed below. While not required for study entry, if participant has genetic testing results available at study entry or any time during the study, the testing result will be collected.

Major Criteria

• > 2 histologically confirmed BCCs or 1 for participant under age 20.
• Odontogenic keratocysts of the jaw confirmed histologically.
• ≥ 3 palmar and/or plantar pits seen at the Screening Visit.
• Bilamellar calcification of the falx cerebri present at less than 20 years of age. Fused, bifid, or markedly splayed ribs.
• First degree relative with GS.
• Patched protein 1 (PTCH1) mutation predicted to be of functional significance in normal tissue.

Minor Criteria

• Macrocephaly.
• Congenital malformations including frontal bossing, cleft lip or palate, "coarse face", moderate to severe hypertelorism.
• Skeletal abnormalities detectable clinically: Sprengel deformity, marked pectus deformity, or marked finger syndactyly.
• Skeletal abnormalities detectable radiographically: bridging of the sella turcica; vertebral abnormalities such as hemivertebrae, fusion or elongation of the vertebral bodies; modeling defects of the hands and feet; flame shaped lucencies of the hands or feet.
• Ovarian fibroma.
• Medulloblastoma.
• The participant is willing to have blood collected for safety and PK testing.
• The participant is willing to abstain from application of a non-study topical medication (prescription or over the counter) to face for the duration of the trial. Moisturizers and emollients are allowed. Participant will be encouraged to use their preferred sunscreen with a sun protector factor (SPF) of at least 30 daily on all exposed skin on the face.
• Participants of childbearing potential must agree to use a medically acceptable, highly effective form of contraception for the entire duration of the study including through the follow-up period.
• The participant is willing to forego treatment of BCCs with anything other than the study IP except when the Investigator believes that delay of treatment of a BCC potentially might
  compromise the health of the participant. During the trial, the only allowed form of BCC treatment is surgical.

Screening

• The participant has previously participated in a clinical trial evaluating sirolimus topical gel within the last 5 years.
• Participants with known hypersensitivity to any of the ingredients in the study medication formulation.
• Participants with current, recent (within five half-lives of the experimental drug or if half-life not known, within the past 6 months prior to Day 0), or planned participation in an experimental drug study while enrolled in this study.
• Participants who are pregnant, breastfeeding or planning to become pregnant during the study including through the follow-up period.
• Participants of childbearing potential who are unwilling or unable to comply with contraception measures.
• The participant has any condition or situation which, in the Investigator's opinion, may put the participant at significant risk, could confound the study results, including disease activity, or could interfere significantly with participation in the study.
• Participants deemed by the investigator as unwilling or unable to remain compliant with all tests and procedures, including photographs of their face, if needed, adherence to the study drug administration regimen, and other protocol-required activities.

Baseline

Participants are eligible to be included in the study only if all the following criteria apply at Day 0, Baseline:

• The participant must have had at least a history of 10 BCCs present on the face, scalp, ears and/or neck (clinically diagnosed and/or biopsy confirmed) within 24 months prior to Randomization/Day 0.
• Female participants of childbearing potential must have a negative urine pregnancy test to participate in the study.

Baseline

Participants are excluded from the study if any of the following criteria apply at Day 0, Baseline:

• The participant has > 20 clinically suspicious lesions on the face at time of randomization.
• The participant has used topical or systemic treatment that might interfere with the evaluation of the study IP.  Among these are use of the following:
  • 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate (topical); itraconazole, SUBA-itraconazole (systemic) within the 3 months prior to Day 0;
  • Hedgehog inhibitors (glasdegib, vismodegib, sonidegib, patidegib) systemically within the 6 months prior to Day 0. Topical Hedgehog inhibitors within the 3 months prior to Day 0;
  • Systemic chemotherapy of any kind within 1 year prior to Day 0;
  • Known inhibitors of the mTOR signaling pathway or systemically within 2 months prior to Day 0;
  • Photodynamic therapy (PDT) to target lesions within 3 months prior to Day 0;
  • Nicotinamide orally (500mg/2 time daily) within 3 months prior to Day 0.
• The participant has previously participated in a clinical trial evaluating an investigational product for treatment of BCCs or GS within 3 months prior to Day 0.
• Participants with an ECOG > 2 at Day 0.
• Participants previously treated for invasive cancer within the past 5 years excluding nonmelanoma skin cancer, Stage I cervical cancer, in situ ductal cell carcinoma of the breast, or chronic lymphocytic leukemia (CLL) Stage 0, at Day 0.

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

• Patients with scleroderma meeting either a, b, c, or d:
• the 2013 ACR criteria;
• 3 out of 5 CREST (calcinosis, Raynauds, esophageal dysmotility, sclerodactyly, telangiectasias);
• triad of Raynauds, nailfold capillary abnormalities, and positive scleroderma autoantibody;
• very early diagnosis of systemic sclerosis (VEDOSS) defined as Raynaud’s, puffy digits, and abnormal nailfold capillaries or positive autoantibody.
• Patients with overlapping autoimmune phenotypes may be included, provided they meet the 2013 scleroderma classification criteria (a).
• This protocol will also allow for recruitment of healthy volunteers for comparison studies.

• Patients without scleroderma will be excluded from the primary disease cohort.
• Healthy volunteers
  (for the comparison cohort) will excluded if they have any autoimmune condition(s) (rheumatic, neurologic, hematologic, etc., at the discretion of the primary investigator or co-investigators).

Eligibility last updated 12/6/21.  Questions regarding updates should be directed to the study team contact.

• 18 years of age or older.
• BMI of 25–39.9 kg/m^2.
• Able to participate fully in all aspects of the study.
• Understood and signed study informed consent.

• Used weight loss medications or participated in a weight loss program within the past 30 days.
• Currently taking medications or supplements known to affect weight, such as prednisone or garcinia cambrogia.
• Weight fluctuations of 5 pounds or more in the past month.
• Have an implanted device (including pacemaker or lap band) in the targeted area of LLLT.
• Have a known active eating disorder.
• Have a known, active, untreated clinically significant psychiatric condition (alcohol or substance abuse, psychosis, bipolar disorder, or depression).
• Have used an investigational drug within 30 days of study enrollment.
• Reports being currently pregnant, lactating, or are of child-bearing potential or are likely to become pregnant during the LLLT treatment phase and are unwilling to use a reliable form of contraception.  Acceptable forms include:
  • Hormonal methods, such as birth control pills, patches, injections, vaginal ring, or implants;
  • Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm);
  • Intrauterine device (IUD);
  • Total hysterectomy or tubal ligation;
  • Abstinence (no sex).
• Htory of any major cardiovascular events including heart valve disease, ongoing angina, cardiac arrhythmias, congestive heart failure, acute coronary syndrome, stroke, transient ischemic attack, or peripheral vascular disease.
• Current uncontrolled hypertension (systolic > 160 mm Hg or diastolic > 95 mm Hg) documented on 2 separate occasions.
• Clinically significant acute or chronic progressive or unstable neurologic, hepatic, renal, cardiovascular, lymphatic, respiratory, or metabolic disease (such as diabetes) or active cancer or are within 1 year of cancer remission.
• Surgical intervention for body sculpting/weight loss, such as liposuction, abdominoplasty, stomach stapling, lap band surgery, etc. within 12 months prior to enrollment.
• Medical, physical, or other contraindications for body sculpting/weight loss.
• Any medical condition known to affect weight levels and/or to cause bloating or swelling.
• Diagnosis of, and/or taking medication for, irritable bowel syndrome.
• Active infection, wound or other external trauma to the areas to be treated with the laser.
• Known photosensitivity disorder.
• Current active cancer or currently receiving treatment for cancer.
• Have a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence.

Eligibility last updated 12/14/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 12/13/22. Questions regarding updates should be directed to the study team contact.

• Adults, ≥ 18 years of age.
• Patients treated with an open surgical hip dislocation at Mayo Clinic from 1997-2018.

• Individuals < 18 years of age.

• Adults, age ≥ 18 years old.
• of Home Enteral Nutrition (HEN) patient receiving at least 90% of energy needs from enteral nutrition.
• BMI > 30.
• History of stroke.
• Weight stable over the past month.

• Diagnosis of cancer undergoing active treatment (chemotherapy, radiation, immunotherapy).
• Life expectancy of less than 6 months.
• Stage IV or higher kidney disease (GFR < 30).

PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA
•INCLUSION

• Patient must be newly diagnosed with B-ALL or is suspected to have ALL.
• Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin Step 1 therapy while awaiting central laboratory eligibility confirmation.
  • NOTE: Bone marrow and/or peripheral blood specimen must be submitted to the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, given that adequate circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to Step 1 without waiting for central confirmation.
• Patients who started any kind of TKI prior to study registration are allowed to proceed on the study if they received no more than 14 days of TKI.

STEP 1 REGISTRATION INCLUSION ELIGIBILITY CRITERIA

• The diagnosis of Philadelphia chromosome positive (Ph+) ALL has been determined locally, and bone marrow and/or peripheral blood was sent for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center.
• Total bilirubin =< 3 mg/dL (unless related to Gilbert's syndrome in which case total bilirubin must be =< 5 mg/dL).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X the institutional upper limit of normal (ULN).
• Estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation).
• Patients with acute organ dysfunction at registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met.
• 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 or on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment.
• Patients with a prior 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 must be class 2B or better.
• Investigators must confirm which TKI patient is to receive.
  • NOTE: Patients with known T315I mutation status should receive ponatinib treatment.
  • NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during Step 1. The investigator must re-specify dasatinib or ponatinib prior to Step 2 randomization and from then on patients must receive the pre-selected TKI only.

STEP 2: RANDOMIZATION
•ELIGIBILITY CRITERIA
•INCLUSION

• Patient must have completed at least 7 of 21 days of protocol-treatment on Arm A prior to randomization.
  • NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI should be initiated prior to randomization.
• Patients who presented with acute organ dysfunction at Step 1 must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN and have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation).
• Investigators must confirm which TKI patient is to receive.
  • NOTE: Patients with known T315I mutation status should receive ponatinib treatment.
• For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization.

STEP 3: REGISTRATION (RE-INDUCTION) - ELIGIBILITY CRITERIA
•INCLUSION

• Institution has received centralized MRD results confirming positive status.
• Patients who presented with acute organ dysfunction must have their total bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN.
• Patients who presented with acute organ dysfunction must have an estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation).
• Investigators must confirm which TKI patient is to receive.
  • NOTE: Patients with known T315I mutation status should receive ponatinib treatment -For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined.

PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA
•EXCLUSION

• Patient must not have received chemotherapy for B-ALL.
• Patients who received up to five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden prior to study registration are eligible.
• Patient must not have unstable epilepsy that requires treatment.

STEP 1 REGISTRATION ELIGIBILITY CRITERIA
•EXCLUSION

• 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 registration 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).
• 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 by abstaining from sexual intercourse from the time of registration, while on study treatment, and until at least six months after the last dose of study treatment.
• Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies can be included.
• Patients must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.

STEP 2: RANDOMIZATION
•ELIGIBILITY CRITERIA
•EXCLUSION

• Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated.

Eligibility last updated 2/9/22. Questions regarding updates should be directed to the study team contact.

• Male and female subjects, 0
  •18 years of age, inclusive.

• Previous personal or family history of kidney disease.
• A concomitant systemic disease that may affect the kidney (e.g., lupus, hepatitis B or C, amyloidosis, diabetes mellitus).

Inclusion Criteria;

• Children with Hypoplastic Left Heart Syndrome who received umbilical cord derived mononuclear cells during cardiac surgery.
• Children with Hypoplastic Left Heart Syndrome, matched in age and cardiac medical/surgical history, who did not receive mononuclear cells during surgery.
• Ages 2 - 5.
• Parent(s) fluent in English and/or Spanish.

• Status post heart transplant.

Other inclusion and exclusion criteria may apply.

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

• Adults ≥ age of 18 years.
• Must have a left ventricular assist device (LVAD).
• Must be able to consent.

• No LVAD.
• Unable to consent.
• Under the age of 18 years.

Eligibility last updated 12/15/21. Questions regarding updates should be directed to the study team contact.

• Patients subject to a laparoscopic hysterectomy procedure necessitating uterine manipulator use,
• Age 18-65.

• Patient known to have a vesicovaginal or rectovaginal fistula.
• Patients who have a documented tape allergy.
• Patients know to have an active pelvic infection.
• Patient diagnosed or known to have fecal incontinence.
• Patients diagnosed or known to have severe external hemorrhoids.
• Patients with a very short perineal body with < 2cm.
• Patients who were found to have a disruption in the occlusive dressing seal at the end of the case (blood soilage).
• Patients necessitating a rectal exam or manipulation as part of the procedure.
• Patient with visible skin irritation or inflammation around the anal orifice.

Eligibility last updated 2/14/22. Questions regarding updates should be directed to the study team contact.

Premenopausal group

• Age 40-48 at the time of original study recruitment.
• Regular menstrual periods for at least 1 year on no hormonal contraception at the time of their participation in the original study.

Postmenopausal group

• Age 52-60 at the time of original study recruitment.
• Confirmed menopausal status at the time of their participation in the original study: no menstrual periods for at least 1 year (but no more than 2 years).

• History of hysterectomy.
• History of surgical, chemical, or radiation-induced menopause (i.e., oophorectomy, aromatase inhibitors, chemotherapy for cancer treatment, or radiation therapy).
• Use of any drug that can affect estrogen production or signaling (e.g., GnRH agonists and antagonists, estrogen receptor modulators, etc.).
• Use of systemic estrogen and/or progesterone (oral contraceptives, contraceptive implants, hormone replacement therapy).
• Use of non-hormonal contraceptive methods that can affect the regularity of menstrual cycles (e.g., intrauterine devices).
• History of hypothalamic or pituitary disease (e.g., pituitary adenomas, empty sella, pituitary surgery, hypothalamic masses).
• Patients who denied future use of biological samples or further contact from the previous listed IRBs.

Eligibility last updated 4/18/22. Questions regarding updates should be directed to the study team contact.

• 18 years of age or older at time of consent.
• Identified with one of 3 Post-Covid Syndrome (PASC) phenotypes at Mayo Clinic Rochester:  
  • fatigue-predominant  (N=20);
  • pain-predominant  (N=20); 
  • orthostasis-predominant  (N=20).
• Not pregnant by subject self-report at time of consent.
• Have the ability to provide informed consent.
• Have the ability to complete all aspects of this trial.
• Have access to an iPhone, iPad, or Android device.  
• Have no contraindicating comorbid health condition which would interfere with the proper use of the Muse-S™ system, as determined by the clinical investigators.

• Individuals < 18 years old.
• Used an investigational drug within the past 30 days.
• Anyone that is not on a stable dose of medication for anxiety, depression or sleep.
• Currently (within the past 3 weeks) been practicing mindfulness training on a weekly/regular basis.
• Currently (within 3 weeks) has been enrolled in another clinical or research program which intervenes on the patients’ QOL, or stress.
• An unstable medical or mental health condition as determined by the physician investigator.

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

• Age 18-45.
• Healthy adults with no medical conditions or previous injuries, trauma, or surgeries that reduce your balance, mobility or strength.
• Able to follow simple directions.
• Willingness to participate in the study.
• No restriction will be placed on gender, race, or ethnicity.

• Current or chronic pain in your shoulders, elbows, hips, knees, ankles, feet, neck or back.
• Use of assistive device such as walker or cane.

• Men and women, ≥ 18 years of age.
• The patients is eligible to undergo WATCHMAN device implant procedure.
• The patient is eligible for short term anticoagulation therapy.
• Ability to tolerate the procedure without the need for general anesthesia as assessed by the treating physician(s).
• Ability to give informed consent for the procedure.
• The patient is able and willing to undergo the procedure under moderate sedation.
• The patient is able and willing to return for required 45-day TEE.

• Patient has contraindication for short term anticoagulation.
• The patient has history of a hypercoagulable state per medical record documentation.
• Pregnancy or planning to get pregnant during the investigation.

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

• Able to give informed consent.
• Adults  > 50 years old.
• No prior cancer diagnosis.

• Individuals < 50 years old.
• Unable or unwilling to provide informed consent.

Eligibility last updated 12/30/21. Questions regarding updates should be directed to the study team contact.

• Patients undergoing percutaneous nephrolithotomy at Mayo Clinic Rochester.
• Adults ≥ 18 years old.
• Ability to receive and respond to electronic text messages.

• Unable or unwilling to provide informed consent.
• Patients who require Intensive Care Unit admission after surgery.
• Patients who have Clavien grade III or greater postoperative complications requiring additional intervention < 30 days after index procedure.

Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.

• Male patients.
• Age 45-80 years, with > 10 years life expectancy.
• Biopsy-confirmed, NCCN (favorable GG2 and unfavorable GG3) intermediate-risk prostate cancer.
• Stage ≤ T2c, N0, M0.
• ISUP Grade Group 2 or 3 disease on TRUS-guided biopsy (minimum 8 cores, combination of systematic and MRI fusion-guided) or in-bore biopsy (minimum 3 cores from each PI-RADS v2 category ≥ 3 lesion). Biopsy reported within 12 months of baseline visit, with minimum 6-week interval between biopsy and baseline.
• PSA ≤ 20 ng/mL reported within 3 months of baseline.
• Treatment naïve.
• Planned ablation volume < 3.0 cm axial radius from the urethra on mpMRI acquired within 6 months of baseline.  

• Inability to undergo MRI or general anaesthesia.
• Suspected tumour > 30 mm from the prostatic urethra.
• Prostate calcifications > 3 mm in maximum extent obstructing ablation of tumour on low-dose pelvic CT:                
  • Criteria subject to additional review and approval by sponsor. Alternatively, prospective TRUS to query calcifications or susceptibility-weighted MRI if available may be used to assess calcifications. Imaging for calcification screening must be dated within 1 year of baseline visit.
• Unresolved urinary tract infection or prostatitis.
• History of proctitis, bladder stones, hematuria, history of acute urinary retention, severe neurogenic bladder.
• Artificial urinary sphincter, penile implant or intraprostatic implant.
• Less than 10 years life expectancy.
• Patients who are otherwise not deemed candidates for RP.
• Inability or unwillingness to provide informed consent.
• History of anal or rectal fibrosis or stenosis, or urethral stenosis, or other abnormality challenging insertion of devices.

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

Inclusion Criteria:

• Age ≥ 18 years.
• Ability to read and write in English.
• Women with newly diagnosed with ovarian, primary peritoneal, or fallopian tube cancer.
• Treatment plan includes chemotherapy.
• Able to provide written voluntary consent before performance of any study related procedure.
• Aim 1 only: after completion of initial chemotherapy.
• Aim 2 only: prior to starting chemotherapy.

• Inability to provide informed consent.
• Exposure to chemotherapy prior to ovarian cancer diagnosis.
• Life expectancy < 3 months or in hospice care or nursing home.

Eligibility last updated 7/8/22. Questions regarding updates should be directed to the study team contact.