• Currently at least 18 years of age. 
• Willing to use study kit to provide fecal specimen.
• Be able to participate fully in all aspects of the study. 
• Have understood and signed study informed consent.

• Have a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence.

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

Eligibility last updated 4/14/23. Questions regarding updates should be directed to the study team contact.

Note: If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study drug. Major surgery is defined as any surgery requiring entrance into a body cavity (eg, chest, abdomen, or brain), organ removal, normal anatomy alteration, or joint replacement. Minor surgery is defined as any surgery in which skin, mucosa,
or connective tissue sections are altered (e.g., biopsy, cataract, endoscopic procedures, etc).

- Have been diagnosed with uveal/ocular or mucosal melanoma;

- Have a known additional malignancy (including all in-situ carcinoma) that is progressing or required active treatment within ≤ 2 years prior to enrollment.  Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have undergone potentially curative therapy or in situ cervical cancer or patients who completed cancer-directed therapy and have no evidence of disease;

- Have active central nervous system metastases and/or carcinomatous meningitis.  Patients with previously treated brain metastases may participate provided they are
stable (without evidence of progression by imaging for at least 4 weeks prior to study Day 1 and any neurologic symptoms have returned to baseline or have been stable for at least 7 days), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study drug. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability;

- Have a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days prior to study Day 1;

- Are receiving systemic steroid > 10 mg of prednisone daily or equivalent or any other immunosuppressive medication at any dose level. Local steroid therapies (e.g., otic,
ophthalmic, intra-articular, or inhaled medications) are acceptable;

- Have an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment;

- Have evidence of active, non-infectious pneumonitis;

- Have active (measurable) and uncontrolled (unresponsive to current therapy) infectious disease (bacterial, fungal, viral, or protozoic);

- Have a history of an acute coronary event (e.g., myocardial infarction) within 3 months prior to study Day 1, uncontrolled and symptomatic coronary artery disease or congestive heart failure New York Heart Association Class III/IV;

- Have an average QTcF interval > 470 msec at Screening;

- Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's
participation for the full duration of the study, or it is not in the best interest of the patient to participate, in the opinion of the treating Investigator;

- Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study;

- Are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 6 months after the last dose of study drug;

- Are known to be human immunodeficiency virus (HIV) positive (or tests positive for HIV 1 or 2 at Screening), unless the following criteria are met: CD4+ lymphocyte count
> 350 µL; Had no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 12 months; Have been on established anti-retroviral therapy for at least 4 weeks; and Have an HIV viral load of < 400 copies/mL prior to study Day 1.

Note: Patients on strong cytochrome P450 (CYP)3A4
inhibitors or strong CYP3A4 inducers must be switched to an alternate effective anti-retroviral therapy regimen prior to study treatment or are excluded if regimen prior to study Day 1 cannot be altered.

- Have uncontrolled hepatitis B infection or hepatitis C infection; or Note: Patients with hepatitis B (positive hepatitis B surface antigen) who have controlled infection (serum hepatitis B virus DNA by polymerase chain reaction that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of hepatitis B virus DNA. 

Note: Patients with hepatitis C (positive hepatitis C virus antibody) who have controlled infection (undetectable hepatitis C virus RNA by polymerase chain reaction either spontaneously or in response to a successful prior course of anti-hepatitis C
virus therapy) are permitted.

- Have received a live vaccine within 30 days of study Day 1; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed.

- For combination arms only: Have received solid organ or hematopoietic stem cell transplant.

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

Eligibility last updated 9/27/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 11/21/23. Questions regarding updates should be directed to the study team contact.

• Ability to understand and willingness to provide informed consent, willingness to comply with all study procedures for the duration of the study.
• Male or female, aged ≥ 18 years.
• Diagnosed with Stage IV metastatic melanoma, or unresectable Stage III.
• Previously progressed (clinical or radiological progression) on at least one prior therapy for metastatic melanoma.
• Uptake of [68Ga]VMT02 or [203Pb]VMT01 by PET or SPECT imaging observed in at least one melanoma tumor site using quantitative imaging analysis compared to reference normal tissue.
• Subjects on prior intravenous therapy (e.g., chemotherapy or checkpoint inhibitors), or prior oral therapy (e.g., BRAF or MEK inhibitors) who demonstrate MC1R positivity during screening are eligible for enrollment, provided that they undergo a wash-out period of 21 days, or 14 days, respectively, prior to Day 1 treatment with [212Pb]VMT01.
• Presence of measurable disease by RECIST v1.1 criteria assessed within 30 days prior to the start of Day 1.
• Ability to lie flat and still for up to two hours for imaging scans; moderate conscious sedation allowed if indicated.
• For females of reproductive potential: use of highly effective contraception for at least one month prior to screening, and agreement to use such a method during study participation and for an additional four weeks after the last administration of an investigational product.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional four weeks after the last administration of an investigational product.
• ECOG performance score of < 2 at Screening.
• Life expectancy of at least 3 months.
• Evidence of sufficient organ function as determined by all of the following:
  • Oxygen saturation > 90% on room air eGFR > 50 mL/min/1.73m^2 by CKD-EPI equation Complete  blood count with differential, within 7 calendar days prior to therapy and off;
  • Growth Factors White blood cells (WBC) > 2500/mm^3;
  • Hemoglobin (Hgb) > 9.0 g/dL;
  • Platelets > 60,000/mm^3;
  • Absolute Neutrophil Count (ANC) > 1,250/mm^3.
• The comprehensive metabolic panel, within seven calendar days prior to Day 1, demonstrating values within the site's upper limit of normal (ULN), with the following exceptions:
  • Alanine aminotransferase (ALT) < 3 x ULN Aspartate;
  • Aminotransferase (AST) < 3 x ULN;
  • Alkaline phosphatase (ALP) < 2.5x ULN.

• Active secondary malignancy.
• Prior treatment (for any reason) with radioactive nuclides; however, imaging tracers are acceptable.
• Pregnancy or breastfeeding a child.
• Active infection.
• Brain metastasis requiring acute therapy of any modality (i.e., surgical or external beam radiotherapy) within two weeks of enrollment or clinical instability, including signs or symptoms of brain edema. Subjects must demonstrate stable or decreasing brain metastasis by a noninvasive imaging scan and must be off steroids or on decreasing doses prior to enrollment.
• Treatment with another investigational drug product (therapeutic IND agents) within the last 30 days.
• Current abuse of alcohol or illicit drugs.
• Existence of any medical or social issues likely to interfere with study conductor that may cause increased risk to the subject or to others; e.g., lack of ability to follow radiation safety precautions.

Eligibility last updated to match clinicaltrials.gov 12/28/22. Questions regarding updates should be directed to the study team contact.

• Patients with:
  • Chronic lymphocytic leukemia (CLL)[;
  • Mantle cell lymphoma (MCL);
  • Waldenstrom macroglobulinemia (WM);   
  • Mantle cell lymphoma (MCL);
  • marginal zone lymphomas (MZL). 
• To begin bruton tyrosine kinase inhibitors (BTKi)treatment (either as a single agent or on combination with others), who are willing to return to Mayo Clinic for ongoing follow-up.

• Patients with known CNS involvement of their B cell malignancy.

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

Eligibility last updated 7/20/23. Questions regarding updates should be directed to the study team contact.

• Women aged 18 years or older.
• If able to become pregnant, negative pregnancy test within 48 hours prior to MBI biopsy procedure.
• Individuals who have previously (within the last 3 years) undergone an MBI study and were found to have at least one breast imaging finding on MBI that was subsequently shown (through additional imaging, biopsy or follow-up) to be benign or probably benign in nature.
• Individuals who had recent conventional imaging work-up including either x-ray mammography, ultrasound, MBI, or MRI of the breast and are found to have at least one breast imaging finding for which biopsy is required or recommended, specifically:
  • Individuals who have a breast abnormality(ies) on imaging with mammography, ultrasound, MBI, or MRI (as per ACR BIRADS 3, or higher) and requiring imaging follow-up or biopsy confirmation.
• Individuals who have agreed to participate in the study and who have signed study-specific informed consent.

• Women who are pregnant.
• Women who are currently lactating or discontinued breastfeeding < 2 months prior to the study.
• Age less than 18 years.
• Women with breast implant(s) in the breast containing the lesion of interest.
• Inability to provide informed consent.

Eligibility last updated 5/12/22. Questions regarding updates should be directed to the study team contact.

• Diagnosis of MCD, FSGS, MN, or IgAN on first diagnostic kidney biopsy, as per specified pathology definitions.
• First diagnostic kidney biopsy within 5 years of study enrollment.
• Access to first kidney biopsy report and/or slides.
• All ages.
• Willingness to comply with study requirements, including intention to fully participate in protocol-specified follow-up at a clinical study site.
• Informed consent and, where age appropriate, informed assent.

• ESKD, defined as chronic dialysis or kidney transplant.
• Institutionalized patient.
• Solid organ or bone marrow transplant recipient at time of first kidney biopsy.
• Diagnosis of any of the following at the time of first diagnostic kidney biopsy:
  • Diabetes mellitus (except gestational or diet controlled);
  • Histopathologic findings of diabetic glomerulosclerosis;
  • Systemic lupus erythematosus;
  • HIV infection;
  • Active malignancy, except for non-melanoma skin cancer;
  • Active Hepatitis B or C infection, defined as positive viral load.

Eligibility last updated 6/24/22. Questions regarding updates should be directed to the study team contact.

• Adult patients with presence of NAFLD associated cirrhosis.
• Cirrhosis: biopsy confirmed or Agile F (F4) score > 0.45.
• NAFLD as the etiology of cirrhosis (any of the following below) NAFLD as an etiology of liver disease will be determined based on presence of any of the following:
  •Biopsy showing > 5% steatosis or
  •CAP > 280 dB/m or MR-PDFF> 5%
  •If CAP < 280 dB/m or MR-PDFF < 5%, then must have type 2 diabetes and or 2 or more features of metabolic syndrome for 5 years (cryptogenic cirrhosis)
• Rationale for Study
  Inclusion Criteria:
  The study will focus on stage 4 fibrosis (i.e. cirrhosis) because they have the highest unmet need. The F4 score is based on LSM, platelets, AST:ALT ratio, diabetes status and sex; many of these parameters are accepted by regulatory standards to represent a non-invasive diagnosis of cirrhosis (54). The attribution of NAFLD as cause of cirrhosis and criteria for cryptogenic cirrhosis meet regulatory standards and are accepted for inclusion in clinical trials (55). NIT-based diagnosis of cirrhosis is included to ensure that data are generalizable to populations seen in routine practice where biopsies are not done and diagnoses made with NIT.

• Refusal to consent.
• Alcohol use > 14/21 gm/week cutoff.
• Other causes of chronic liver disease.
• MELD > 12.
• Hepatic and extrahepatic cancers expected to limit life expectancy < 2 yrs.
• Prior hepatic resections, TIPS, splenic embolization.
• Prior decompensation events.
• Inability to fit in to MRI (failed hula-hoop test).
• Contraindications for MRI.
• General contraindication for MRI contrast (GFR < 30 ml/min).
• Pregnancy.

Rationale for exclusion criteria: The exclusion criteria are designed to meet ethical (refusal to consent), etiology (alcohol and other etiologies), clinical (factors likely to lead to death before a liver event e.g. cancers) and MRI-related (hula-hoop, GFR that precludes MRI) factors.

Eligibility last updated 7/27/22. Questions regarding updates should be directed to the study team contact.

• High-risk disease defined as an IPI score of 4 or 5 at initial diagnosis.
• Histologically confirmed LBCL based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including one of the following:
  • Diffuse large B-cell lymphoma, NOS;
  • High-grade B-cell lymphoma (HGBL) (including HGBL with MYC and BCL2 and/or BCL6 rearrangements (DHL/THL) based on FISH analysis, and HGBL-NOS);
    • Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.
• Ann Arbor Stage III or IV disease.
• Have received only 1 cycle of R-chemotherapy.
• At least 1 measurable lesion per the Lugano Classification {Cheson 2014} on anatomical imaging such as computed tomography (CT) imaging (functional imaging such as PET may not be used to identify a measurable lesion). A measurable lesion is defined as greater than 1.5 cm LDi for lymph node and greater than 1.0 cm LDi for extranodal lesion.
• Adequate tumor biopsy specimen available for central pathology review (detailed sample collection requirement is in central pathology laboratory manual).
• Age 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization;
  • Note: ECOG > 1 at diagnosis is acceptable.
• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function as indicated by:
  • Absolute neutrophil count (ANC) ≥ 1000/μL;
  • Platelet count ≥ 75,000/μL;
  • Absolute lymphocyte count ≥ 100/μL;
  • Creatinine clearance (as estimated by any local institutional method) ≥ 60 mL/minute;
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 x ULN if documented liver involvement of lymphoma;
  • Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s Syndrome or documented LBCL liver or pancreatic involvement where ≤ 3.0 times the ULN;
  • Left ventricular ejection fraction (LVEF) ≥ 50% and no evidence of clinically significant pericardial effusion, and no clinically significant abnormal electrocardiogram (ECG) findings;
  • No evidence of Grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] 5.0) or greater pleural effusion or ascites (subjects with Grade 1 ascites or pleural effusion are eligible);
  • Baseline oxygen saturation > 92% on room air.
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).

• Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.
• The following WHO 2016 subcategories by local assessment:
  • T-cell/histiocyte-rich LBCL;
  • Primary DLBCL of the CNS;
  • Primary mediastinal (thymic) LBCL;
  • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma;
  • Burkitt lymphoma.
• History of severe immediate hypersensitivity reaction attributed to aminoglycosides.
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple bacterial infections are permitted if responding to active treatment and after consultation with the Kite medical monitor.
• History of acute or chronic active hepatitis B or C infection. If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
• Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a CD4 count > 200 cells/uL.
• Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted.
• Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of central nervous system (CNS) involvement of lymphoma.
• Presence of CNS disorder such as dementia, autoimmune disease with CNS involvement, cerebral edema with confirmed structural defects by appropriate imaging, or seizure disorders requiring active anticonvulsive medication. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.
• Presence of cardiac atrial or ventricular lymphoma involvement.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months before enrollment.
• Presence of primary immunodeficiency A.
• History of autoimmune disease (eg, Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
• History of non-line associated, clinically significant (CTCAE 5.0 Grade 2 or greater) deep vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6 months of randomization.
• Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study, including the lymphodepletion chemotherapy (cyclophosphamide or fludarabine).
• Live vaccine ≤ 6 weeks before the planned start of the lymphodepletion chemotherapy regimen.
• Females of childbearing potential who are pregnant or breastfeeding (due to potentially dangerous effects of the preparative chemotherapy on the fetus or infant).
• Not willing to practice birth control from the time of consent through at least 6 months after the last dose of axicabtagene ciloleucel or SOCT 20) In the investigator’s judgment, the subject is unlikely to complete all study-specific visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Eligibility last updated 8/2/22. Questions regarding updates should be directed to the study team contact.

• Over 18 years of age.
• Able to provide consent.

• Individuals < 18 years of age.
• Any subjects with head size circumference greater than 56 cm will be excluded in studies to assess positional brain shift.
• History of epilepsy.
• Pregnant.
• Present of ferromagnet objects or non-MR-safe medical devices or implants.

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

Eligibility last updated 12/11/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria:

• Patients ±18 years of age.
• Ability to provide written, informed consent.
• Confirmed decompensated cirrhosis of any etiology.
• Currently taking lactulose daily for management of hepatic encephalopathy.
• Participant has a smartphone device with access to internet connection.

Exclusion Criteria: 

• Recent change in dosing of opioid medication (within 30 days of consenting).
• Inflammatory Bowel Disease or presence of intestinal obstruction.
• Previous Colorectal Surgery.
• Active diarrheal illness.
• Lack of smartphone or other smart device at home.
• Presence of overt HE at the time of enrollment.
• Lactulose intolerance.
• History of cognitive impairment.

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

Eligibility last updated 9/13/23. Questions regarding updates should be directed to the study team contact.