• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• The patient must have an ECOG performance status of 0 or 1.
• The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection).
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
• Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
  • By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm);
  • By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible);
  • Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen;
    • ** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.
  • The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive;
  • The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
• Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or documented bilateral oophorectomy.
• The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.
• The patient must have recovered from surgery with the incision completely healed and no signs of infection.
• Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.

• Definitive clinical or radiologic evidence of metastatic disease. -pT2
  •pT4 tumors including inflammatory breast cancer.
• Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
• Patient had a mastectomy.
• Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible).
• Paget's disease of the nipple.
• Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible).
• Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible).
• Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible).
• Treatment plan that includes regional nodal irradiation.
• Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry. (Short course endocrine therapy of less than 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.
• Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible.
• Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
• Prior breast or thoracic RT for any condition.
• Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
• Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment.
  • Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
• Use of any investigational product within 30 days prior to study entry.

Eligibility last updated 9/20/21. Questions regarding updates should be directed to the study team contact.

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
• The patient must have an ECOG performance status of 0 or 1.
• The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection).
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
• Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
• The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
  • By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm);
  • By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible);
  • Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen;
    • ** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.
  • The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive;
  • The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
• Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or documented bilateral oophorectomy.
• The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.
• The patient must have recovered from surgery with the incision completely healed and no signs of infection.
• Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.

• Definitive clinical or radiologic evidence of metastatic disease. -pT2
  •pT4 tumors including inflammatory breast cancer.
• Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
• Patient had a mastectomy.
• Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible).
• Paget's disease of the nipple.
• Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible).
• Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible).
• Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible).
• Treatment plan that includes regional nodal irradiation.
• Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry. (Short course endocrine therapy of less than 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.
• Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18).
• Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible.
• Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
• Prior breast or thoracic RT for any condition.
• Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
• Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment.
  • Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
• Use of any investigational product within 30 days prior to study entry.

Eligibility last updated 9/20/21. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Patient has undergone office-based evaluation for hematuria (CT, ultrasound, cystoscopy).

• Patient has known cancer outside of the target cancer 5 years prior to current collection (not including basal cell or squamous cell skin cancers; if patient has not been seen or if information is not available, the patient is eligible).
• Patient has recurrent bladder cancer.
• Patient has ever been previously diagnosed with UTUC (Upper Tract Urothelial Carcinoma) prior to bladder resection.
• Patient has prior diagnosis of bladder cancer for which intravesical immunotherapy (BCG) or chemotherapy (Mitomycin, Valrubicin) was provided.
• Patient has received chemotherapy class drugs for the treatment of cancer in the 5 years prior to current collection.
• Patient has had any prior radiation therapy to the target lesion prior to current collection.
• Patient has had a biopsy to the target organ and/or lesion within 3 days before collection.
• Patient has undergone cystectomy.
• Patient has transurethral instrumentation (placement of urinary catheter) within 7 days prior to urine collection.
• Patient has had a urinary tract infection within 14 days prior to urine collection.
• Patient has chronic indwelling urinary catheter 
• Patient has prior diagnosis of bladder cancer for which prior resection of tumor was performed.

Eligibility last updated 6/29/22. Questions regarding updates should be directed to the study team contact.

• Prior TNFi biologic treatment – Patient has active, moderate-high disease activity RA (CDAI ≥ 10 and HAQ ≥ 0.5) despite the use/experience for ≥ 3 months of a TNFi-biologic OR discontinued the medication(s) due to intolerability or toxicity irrespective of treatment duration prior to the first dose of study drug; AND
• Glucocorticoid and NSAID treatment
  •If receiving glucocorticoids (≤ 10 mg/day of prednisone of equivalent) or NSAIDs, on stable doses for ≥ 2 weeks prior to randomization; AND
• Insurance
  •Insurance plan or patient assistance program allows access to at least 1 drug in each of the two treatment strategies for 1 year trial duration. Participants will be allowed to continue their conventional synthetic DMARD (csDMARD) therapy if they had been using it for ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, and leflunomide (TNFi-biologic and tsDMARD) through insurance plan or a patient assistance program/plan.

• Prior treatment with more than three biologics, defined as TNFi-biologic or non-TNFi biologic.
• Prior treatment with targeted synthetic DMARD.
• Concomitant use of cyclosporine, or azathioprine within 2-months before randomization.
• History of sensitivity to all 4 non-TNF-biologic or a targeted synthetic DMARD.
• Glucocorticoid injection (intravenous, intramuscular, or intraarticular) within 1 month of study entry.
• Live vaccine within 90 days of study entry.
• Acute infection treated with parenteral antibiotics or hospitalization within 1 month or with oral antibiotics within 2 weeks of study entry; or chronic infections requiring long-term antibiotic suppressive therapy.
• History of HIV or opportunistic infections.
• New York Heart Association Class III or IV heart failure.
• Latent TB not treated with anti-mycobacterial medication.
• Untreated Hepatitis B or C infection.
• History of deep venous thrombosis or pulmonary embolism.
• Pregnant or nursing women.
• History of herpes zoster or shingles.

Eligibility last updated 6/1/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 7/26/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 1/13/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 4/17/23. Questions regarding updates should be directed to the study team contact.

• ASA classification I to III, older than or equal to 18 years old.
• All genders.
• Presenting for primary total knee replacement for degenerative joint disease.
• Patient capable of providing their own informed consent.

• Vulnerable study populations including prisoners.
• Patients with a contralateral total knee arthroplasty < 2 years prior to the index procedure.
• Compromised health barring them from proceeding with surgery including acute or chronic kidney injury identified pre-operative.
• Patients unable to provide their own informed consent.
• Pregnancy.
• Patients with documented chronic pain syndromes.
• Patients with a history of prolonged daily opioids (more than 1 month) with an oral morphine equivalent of greater than 5mg/day.
• BMI > 45 kg/m^2.
• Allergies to any component of the study medications, including specific history of type 1 hypersensitivities to any NSAID.
• Patients with impaired cognitive function.
• Major systemic illnesses such as severe renal (estimated glomerular filtration rate less than 50ml/min), coronary artery disease requiring a bypass graft (CABG), other cardiac problems including congestive heart failure (CHF New York Heart Association class III to IV), or severe hepatic disorders defined as current or past diagnosis of acute/subacute liver necrosis, acute hepatic failure, chronic liver disease, liver abscess, hepatic coma, hepatorenal syndrome and other disorders of the liver.

Eligibility last updated 10/12/21. Questions regarding updates should be directed to the study team contact.

• Pathologic findings supporting the clinical impression of anaplastic thyroid  carcinoma. Diagnosis may include consistent with or suggestive of terminology  associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous  carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present.
• Must have a BRAFV600E mutation-positive tumor, as determined by BRAF V600E  immunohistochemistry on tumor tissue, genetic/molecular testing of tumor, or cell free  (cf)NDA liquid biopsy.
• Have measurable disease based on RECIST 1.1.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Total bilirubin ≤ 3 x ULN for  patients with Gilbert's syndrome.
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase  [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])  ≤ 2.5 x ULN, (5 x ULN for patients with concurrent liver metastases).
• Serum creatinine ≤ within 1.5 x ULN.
• Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L.
• Platelets ≥ 100 x 10^9/L.
• Hemoglobin ≥ 9.0 g/dL or 5.6 mmol/L.
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless  participant is receiving anticoagulant therapy as long as PT or activated partial  thromboplastin time (aPTT) is within therapeutic range of intended use of  anticoagulant.
• Subjects must be willing to undergo tumor biopsy prior to and after the run-in with dabrafenib/trametinib (DT), unless in the opinion of the treating physician, a biopsy is not feasible or safe. Subjects must be willing to ultimately undergo surgery if  their tumor becomes surgically resectable. Research subjects retain the right to  refuse any research interventions.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.  Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• A male participant must agree to use a contraception of this protocol during the  treatment period and for at least 8 months after the last dose of study treatment and  refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant, not  breastfeeding, and at least one of the following conditions applies:  
  • Not a woman of childbearing potential (WOCBP); OR
  • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after the last dose of study treatment.

• Significant cardiovascular impairment: history of congestive heart failure greater  than New York Heart Association (NYHA) class II.
• Untreated brain metastases.
• Prior chemotherapy within < 1 week prior to study day 1 or patients who have not  recovered (i.e., ≤ grade 2) from adverse events due to a previously administered  agent, except for patients who have been on dabrafenib/trametinib (DT) according to  the standard run-in outlined in the trial schema.
• Has 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.
• History of human immunodeficiency virus (HIV) or active hepatitis B (chronic or acute)  or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive  anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. However,  patients with past or resolved hepatitis B virus (HBV) should be monitored for  reactivation by a specialist. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic  acid (RNA).
  • Note: no testing for HIV, hepatitis B and hepatitis C is required unless  mandated by local heath authority.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose  of study drug. Administration of killed vaccines is allowed.
• Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required  steroids or has current pneumonitis/interstitial lung disease.
• Has known psychiatric or substance abuse disorders that would interfere with  cooperation with the requirements of the trial.
• Females who are breastfeeding or pregnant at screening or baseline (as documented by a positive beta-human chorionic gonadotropin [beta-hCG] (or human chorionic gonadotropin  [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG [or hCG]). A women of childbirth potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to the first infusion will be excluded. If the urine test is  positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• More than 30 days of DT therapy prior to enrollment.
• A known history of retinal vein occlusion (RVO), central serous retinopathy (CSR), uncontrolled glaucoma or ocular hypertension.

Eligibility last updated 9/27/21. Questions regarding updates should be directed to the study team contact.

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

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

• Women age ≥ 18 years.
• Eastern Cooperative Oncology Group performance status 0-2 (Karnofsky >60%).
• Patients with metastatic breast cancer.
• HER2 (human epidermal growth factor receptor 2)-positive breast cancer prospectively determined on the primary tumor by a local pathology laboratory and defined as:
  • Immunohistochemistry (IHC) score of 3+ and/or positive by ISH (defined by In Situ Hybridization ratio of ≥ 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies). Both IHC and ISH assays will be performed; however, only one positive result is required for eligibility.
• Estrogen/progesterone receptor positive OR negative disease allowed.
• Patients must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Patients that have failed at least one anti-HER2 therapy in the metastatic setting.
• Patients must have normal organ and marrow function as defined below:
  • absolute neutrophil count ≥ 1,500/mL;
  • platelets ≥ 100,000/mL;
  • total bilirubin ≤ institutional upper limit of normal (ULN);
  • aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 5 ≤ X institutional ULN;
  • creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
• Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram (preferred) or multigated acquisition (MUGA) scans.
• Willing and able to comply with the requirements of the protocol.
• Patient is able to take oral medication.
• Signed informed consent.
• Female patients of childbearing potential must be willing to use one highly effective form of hormonal contraception or two effective forms of nonhormonal contraception.
• Contraception must continue for the duration of study treatment and for 7 months after the last dose of study treatment. The above contraception is not a requirement in the case of any of the following:
  • The patient, or partner of the patient, is surgically sterilized;
  • The female patient is > 45 years of age and is postmenopausal (has not menstruated for at least 12 consecutive months;
  • The patient truly abstains from sexual activity and when this is the preferred option to avoid conception and contraception and/or usual lifestyle of the patient.

• Metastatic breast cancer patients who are HER2 positive and have NOT progressed on at least one prior HER2-targeted therapies for metastatic disease -Patients who have not recovered from CTCAE, v. 4.03 grade 2 or higher toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment. Subjects receiving weekly therapy must have a washout period from prior chemotherapy of as least one week. Washout period for chemotherapy administered every 2, 3, or 4 weeks will be 2, 3, and 4 weeks respectively, provided subject has recovered from toxicities of prior therapy such that retreatment is appropriate.
• Patients must be at least two weeks from prior RT.
• Patients must have a one-week washout period from prior hormonal therapy (e.g., testosterone, estrogen, progestin, gonadotropin-releasing hormone antagonist).
• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability. No concurrent anti-cancer treatment of any type.
• Patients with known germline BRCA 1 or BRCA 2 mutations.
• Patient has undergone prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor.
• Prior treatment of a total doxorubicin > 360 mg/m^2 (or equivalent).
• Patient has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected).
• Patient has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). -Chronic immunosuppressive therapies including systemic corticosteroids or concurrent short-term use of immunosuppressive therapies is not allowed. Short- term corticosteroid use must be discontinued at least 2 weeks prior to study treatment.
• Patients with known grade 2 or greater allergic reactions attributed to compounds of similar chemical or biological composition to niraparib are ineligible for study enrollment.
• Patients with known grade 2 or greater allergic reactions attributed to compounds of similar chemical or biological composition to herceptin are ineligible for study enrollment.
• Patient is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 7 months after the last dose of study treatment. -History of non-breast malignancies within the 5 years prior to study entry, except for the following:
  • Carcinoma in situ (CIS) of the cervix;
  • CIS of the colon;
  • Melanoma in situ;
  • Basal cell and squamous cell carcinomas of the skin.
• Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection that requires systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
• Cardiopulmonary dysfunction as defined by any of the following prior to randomization:
  • History of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.0) Grade ≥3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class ≥ II;
  • Angina pectoris requiring anti-angina medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease -High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third degree AV-block]);
  • Significant symptoms (Grade ≥ 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia;
  • Myocardial infarction within 12 months prior to randomization.
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg).
• Evidence of transmural infarction on ECG.
• Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening.
• Requirement for oxygen therapy.

Eligibility last updated 9/28/21. Questions regarding updates should be directed to the study team contact.

• Aged 18 years of age or older.
• Patients who have had a recent episode of COVID-19 and who present to the Post COVID-19 Clinic at Mayo Clinic Rochester.   
• Access to smartphone (iOS or Android operating systems).
• Ability to complete study questionnaires and provide voice samples using a smartphone application.

• Known history of voice disorder either primary or secondary to neuromuscular or other pathology.
• Cognitively impaired patients.
• Prisoners.
• Non-English speakers.
• Currently on another study assessing depression or quality of life.

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

• Patients must be ≤ 50 years of age at the time of enrollment.
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification are eligible to enroll on the study based upon Stage, Group, and age, as below. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) Classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants.
• ERMS -Stage 4, group IV, ≥ 10 years of age.
• ARMS -Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age.
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study.
• Creatinine clearance or radioisotope glomerular filtration rate (GFR)  7 ≥ 0 mL/min/1.73 m^2; or
• A serum creatinine based on age/gender as follows:
  • Age | Maximum serum creatinine (mg/dL)
  • 1 month to < 6 months | 0.4 mg/dL (male); 0.4 mg/dL (female);
  • 6 months to < 1 year 0.5 mg/dL (male) | 0.5 mg/dL (female);
  • 1 to < 2 years 0.6 mg/dL (male) | 0.6 mg/dL (female);
  • 2 to < 6 years 0.8 mg/dL (male) | 0.8 mg/dL (female);
  • 6 to < 10 years 1 mg/dL (male) | 1 mg/dL (female);
  • 10 to < 13 years; 1.2 mg/dL (male) | 1.2 mg/dL (female);
  • 13 to < 16 years; 1.5 mg/dL (male) | 1.4 mg/dL (female);
  • ≥ 16 years; 1.7 mg/dL (male) | 1.4 mg/dL (female).
  • The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR39 utilizing child length and stature data published by the CDC.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
• If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

• Patients with evidence of uncontrolled infection are not eligible.
• RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed.
• Patients with central nervous system involvement of RMS as defined below:
  • Malignant cells detected in cerebrospinal fluid;
  • Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed);
  • Diffuse leptomeningeal disease;
  • Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment;
  • Note: the following exception:
  • Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation.
  • Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy.
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.

Eligibility last updated 9/29/21. Questions regarding updates should be directed to the study team contact.

• Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10% CD30 expression by immunohistochemistry in the following subtypes (by local review): nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma.
• Patients will be stratified by presence or absence of TFH phenotype (i.e., diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of pathology. Determination of TFH phenotype can be defined by expression of two or more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by immunohistochemistry.
• Measurable disease as defined by the Lugano criteria.
• No prior systemic therapy for lymphoma (excluding corticosteroids).
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to registration is required.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Platelet count ≥ 75,000/mm^3 (≥ 50,000/mm^3 if secondary to bone marrow involvement from lymphoma per investigator assessment; the first 12 patients on each arm of the study must have platelets ≥ 75,000/mm^3 regardless of bone marrow involvement).
• Absolute neutrophil count (ANC) ≥ 1,000/mm^3.
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN) * Except in subjects with documented liver involvement by lymphoma.
• Calculated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula.
• Total bilirubin ≤ 2.0 x ULN * Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement by lymphoma.
• Archival tissue must be available for submission.
• No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Those who are seropositive (e.g., hepatitis B core antibody [Ab] positive) are permitted if they are negative by polymerase chain reaction (PCR). Those who are seropositive for hepatitis B and are negative for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed antiviral therapy. Those who have hepatitis C Ab positivity who have completed curative therapy for hepatitis C with negative hepatitis C PCR are eligible.
• Patients with history of HIV are eligible if they have an undetectable viral load for at least 6 months.
• No active uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment).
• Patients with Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted.
• Patients must have documented left ventricular ejection fraction of ≥ 45%.
• No significant active cardiac disease within the previous 6 months including: 
  • New York Heart Association (NYHA) class III or IV congestive heart failure;
  • Unstable angina or angina requiring surgical or medical intervention; and/or
  • Myocardial infarction.

• Patients with expression of CD30 in ≥ 10% of the tumor (based on local immunohistochemistry review) regardless of histology will not be permitted.
• Patients with a diagnosis of other PTCL subtype histologies other than those specified in the inclusion criteria are excluded including large cell transformation of mycosis fungoides.
• Patients known to have HTLV 1/2.
• Patients with known central nervous system involvement.
• No concurrent malignancy requiring active therapy within the last 3 years with the exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer. Adjuvant hormonal therapy for cancer previously treated for curative intent is permitted.
• No contraindication to any drug in the chemotherapy regimen, including neuropathy ≥ grade 2.
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.

Eligibility last updated 9/30/21. Questions regarding updates should be directed to the study team contact.

• Age 18 or older.
• Patients with paroxysmal atrial tachyarrhythmias with and without polyuria as a manifestation of their tachyarrhythmia episode.
• Documentation of their paroxysmal atrial tachyarrhythmia episode.

• Patients who are unable to manage the logistics of participating in the study (coming to Saint Mary’s Hospital ot have their blood drawn and urine sample collected during their atrial tachyarrhythmia episode).
• Chronic kidney disease stage 4 or higher.
• Clinical history of heart failure.

Eligibility last updated 10/1/21. Questions regarding updates should be directed to the study team contact.

Key

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

Eligibility last updated 5/18/23. Questions regarding updates should be directed to the study team contact.

• Between 18 and 85 years of age (inclusive) at the initial screening visit.
• Meets 2011 consensus criteria for svPPA (Gorno-Tempini et al. 2011).
• MRI at screening is consistent with the underlying svPPA with no large strokes or severe white matter disease (Fazekas Grade ≤ 2; Fazekas et al. 1987);
• CDR® plus NACC FTLD (Miyagawa et al. 2020) global score at screening ≤1.
• The following medications are allowed, but must be stable for 2 months prior to the initial screening visit:
  • Food and Drug Administration (FDA)-approved Alzheimer's disease (AD) medications;
  • FDA-approved psychotropic medications;
  • Other medications (except those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to the initial screening visit.
• Has a reliable study partner who agrees to accompany the participant to visits, and spends at least 5 hours per week with the participant.
• Agrees to 2 LPs.
• Signed and dated written informed consent obtained from the participant and the participant's study partner in accordance with local Institutional Review Board (IRB) regulations.
• WOCBP must agree to abstain from sex or use highly effective birth control that includes two methods of contraception (one of which must be a barrier method) for the duration of the screening period, the RDBPC treatment period, and for 30 days after the last dose of study drug (active or placebo).
• Males must agree to abstain from sex with WOCBP or use an adequate method of contraception for the duration of the RDBPC treatment period and for 90 days after the last dose of study drug (active or placebo).
• Able to swallow pills whole without crushing or chewing.

• A clinical diagnosis of probable AD (McKhann et al. 2011) or previous biomarker evidence of AD biology using amyloid positron emission tomography (PET) imaging, CSF amyloid beta (A?)/total tau (t-tau) ratio, CSF/plasma amyloid beta isoform with 40 amino acid residues (Aβ40)/amyloid beta isoform with 42 amino acid residues (Aβ42) ratio, or plasma phosphorylated tau [phosphorylated tau at residue 181 (p-tau181) and phosphorylated tau at residue 217 (p-tau217)] assessments.
• A clinical diagnosis of a comorbid FTLD-associated clinical syndrome other than svPPA, including:
  • logopenic primary progressive aphasia (lvPPA; Gorno-Tempini et al. 2011);
  • non-fluent/agrammatic variant primary progressive aphasia (nfvPPA; Gorno-Tempini et al. 2011);
  • behavioral variant for frontotemporal dementia (bvFTD; Rascovsky et al. 2011). Patients who meet diagnostic criteria for svPPA (Gorno-Tempini et al. 2011) may still be included if they have a secondary diagnosis of bvFTD, so long as the PI can reasonably attribute their disinhibition, dietary changes, compulsions, and/or loss of empathy to anterior temporal lobe atrophy (Seeley et al. 2005) and MRI is consistent with right anterior atrophy (or left temporal atrophy in participants with suspected right hemispheric language dominance);
  • progressive supranuclear palsy (PSP; Höglinger et al. 2017); e. corticobasal syndrome (CBS; Armstrong et al. 2013).
• Any other medical condition other than FTLD that is likely to account for cognitive or behavioral deficits (e.g., uncontrolled seizure disorder, stroke, vascular dementia, substance abuse or alcoholism, Lewy body disease).
• History of uncontrolled thyroid disease or evidence thereof [i.e., abnormal free thyroxine (T4) levels and thyroid stimulating hormone (TSH) > 10 milli-international units (mIU)/liter (L) at screening (confirmed by repeat)].
• Serious autoimmune disease, or ongoing immunocompromised state.
• History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof at screening).
• History or presence of gastrointestinal (GI) or other disease known to interfere with absorption, distribution, metabolism, or excretion of drugs, or a history of surgery known to interfere with absorption or excretion of drugs (i.e., gastric bypass).
• Within 1 year prior to initial screening visit or between screening and baseline (pre-dose Day 1), any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of, unstable angina; or syncope.
• History of major psychiatric illness or untreated depression that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data.
• Neutrophil count <1,500/cubic millimeter (mm3), platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin (TBL) >1.5 x ULN, alanine aminotransferase (ALT) >1.5 x ULN, aspartate aminotransferase (AST) >1.5 x ULN, or international normalized ratio (INR) >1.2 at screening (confirmed by repeat).
• Evidence of any clinically significant findings on screening or baseline evaluations which, in the opinion of the PI would pose a safety risk or interfere with appropriate interpretation of study data.
• Corrected QT interval by Fridericia (QTcF) ≥ 470 milliseconds (msec) or uncontrolled arrhythmia or frequent premature ventricular contractions (PVCs; >5/minute) or Mobitz Type II second or third degree atrioventricular (AV) block or left bundle branch block or right bundle branch block with a QRS duration ≥ 150 msec or intraventricular conduction defect with a QRS duration ≥ 150 msec or evidence of acute or sub-acute myocardial infarction or ischemia or other ECG findings at screening or baseline that, in the PI's opinion, would preclude participation in the study.
• Pathologic renal findings at screening as defined by the presence of either of the following criteria:
  • Estimated glomerular filtration rate (eGFR) [determined by the Modification of Diet in Renal Disease (MDRD) Study equation] < 30 milliliter (mL)/minute/1.73 square meter (m^2). The MDRD Study equation is as follows: eGFR (mL/minute/1.73 m^2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American), where Scr = serum creatinine in mg/deciliter (dL) as measured by a method calibrated to an isotope dilution mass spectrometry (IDMS) reference method;
  • Serum creatinine ≥ 2.5 mg/dL;
  • Hemoglobin A1C > 7.5% at screening (confirmed by repeat);
• Current or recent history (within four weeks prior to initial screening visit) of a clinically significant bacterial, fungal, or mycobacterial infection.
• Current clinically significant viral infection, including "known" positive status for human immunodeficiency virus (HIV) (i.e., based on prior testing; HIV testing will not be performed as part of the screening evaluations for this trial).
• Major surgery within four weeks prior to initial screening visit.
• Blood transfusion within 4 weeks of initial screening visit.
• History of stem cell treatment.
• Any contraindication for MRI or unable to tolerate MRI at screening.
• Any contraindication to or unable to tolerate LP at screening, including the use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to the initial screening visit.
• Participants who, in the opinion of the PI, are unable or unlikely to comply with the dosing schedule or study evaluations.
• Prior treatment with verdiperstat.
• Treatment with another investigational drug within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with investigational drugs other than verdiperstat while on study will not be allowed.
• Treatment with systemic corticosteroids or steroid sparing systemic immunosuppressive agents within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with systemic corticosteroids or other systemic immunosuppressive therapy while on study will not be allowed.
• Treatment with strong inhibitors of CYP1A2 (i.e., ciprofloxacin, enoxacin, fluvoxamine) within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with strong inhibitors of CYP1A2 while on study will not be allowed.
• Known hypersensitivity to the inactive ingredients in the study drug products (active or placebo).
• Known to be pregnant or lactating, or positive pregnancy test at screening or baseline (pre-dose Day 1).
• Cancer within 5 years of initial screening visit, except for basal cell carcinoma.
• History or evidence at screening of known disease-associated mutations associated with FTLD without trans-activation response deoxyribonucleic acid-binding protein of 43 kilodaltons (TDP-43) inclusions [e.g., mutations in the genes encoding chromatin-modifying protein/charged multivesicular body protein B2 (CHMPB2), microtubule-associated protein tau (MAPT), or fused in sarcoma (FUS)].

Eligibility last updated 3/7/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 6/28/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 8/16/22. Questions regarding updates should be directed to the study team contact

• Willing and able to provide written informed consent.
• Males or females, ≥ 18 years of age.
• Receiving a human leukocyte antigen (HLA) matched allogeneic peripheral BMT from a family or unrelated donor, HLA-mismatched related or unrelated donor, or haploidentical donor.
• Diagnosed with 1 of the following underlying diseases:
  • Refractory anemia;
  • Refractory anemia with ringed sideroblasts;
  • Refractory cytopenia with multilineage dysplasia;
  • Refractory cytopenia with multilineage dysplasia and ringed sideroblasts;
  • Refractory anemia with excess blasts
    •1 (5-10% blasts);
  • Refractory anemia with excess blasts
    •2 (10-20% blasts);
  • Myelodysplastic syndrome, unclassified;
  • Myelodysplastic syndrome associated with isolated del (5q);
  • Chronic myelomonocytic leukemia;
  • Lymphoma (including Hodgkin's) with chemosensitive disease (i.e., response to chemotherapy) and receiving a related donor transplant;
  • Aplastic anemia;
  • Primary or secondary myelofibrosis.
• Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
• Acute lymphoblastic leukemia, in first or second complete remission.
• Acute undifferentiated leukemia in first or second remission.
• Acute biphenotypic leukemia in first or second complete remission.
• Chronic myelogenous leukemia in either chronic or accelerated phase.
• One of the following myelodysplastic syndrome(s) defined by the following:
  • Receiving myeloablative or reduced-intensity conditioning regimens.
• Adequate renal and hepatic function, within 6 weeks of initiation of conditioning, as measured by:
  • Hepatic (within 72 hours of Day 0): alanine aminotransferase;
  • Renal (within 72 hours of Day 0): Serum creatinine within normal range for age or if serum creatinine above ULN range for age, a creatinine clearance [CrCl]) ≥60 mL/min.;
  • Baseline blood samples drawn for serum Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 14 days before randomization, with results available prior to randomization;
  • Baseline Toxoplasma serologies available within 6 weeks prior to randomization;
  • Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency testing with no evidence of G6PD deficiency performed within 6 weeks prior to randomization.
• Female subjects of child-bearing potential < 2 years post-menopausal must agree to and comply with using 1 barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence while participating in this study. Male subjects must be vasectomized, abstain from sexual intercourse, agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm while participating in the study and for 120 days from the last IV dose of study drug.

• Diagnosis of AML not in morphological remission.
• Diagnosis of chemotherapy-resistant lymphoma.
• Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of screening.
• Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤ 40%, LVEF > 40% but fails to improve with exercise, or shortening fraction ≤ 26%.
• Personal or family history of Long QT interval on ECG (QT) syndrome or a prolonged QT interval corrected (QTc) interval (> 470 msec in males and > 480 msec in females); or concurrent administration of terfenadine, cisapride, astemizole, erythromycin, pimozide, or quinidine.
• Diagnosed reduced lung function with either diffusion capacity (corrected for hemoglobin), forced expiratory volume 1, forced vital capacity ≤ 45% of predicted value, or O2 saturation ≤ 85% on room air.
• Suspected or documented PCP within 2 years of screening.
• Positive baseline serum Platelia GM EIA (≥ 0.5) and/or β-D glucan assay (≥ 80 pg/mL).
• Receipt of previous allogeneic BMT.
• Planned receipt of cord blood for transplantation.
• Planned peripheral blood or marrow autograft.
• Underlying diagnosis of multiple myeloma.
• Grade 2 or higher ataxia, tremor, motor neuropathy, or sensory neuropathy, per NCI CTCAE version 5.0.
• History of severe ataxia, neuropathy or tremors; or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease or Huntington's disease).
• Planned or ongoing therapy at screening with a known neurotoxic medication for a complete list of prohibited neurotoxic medications).
• Known hypersensitivity to Rezafungin for Injection, any echinocandin, fluconazole, posaconazole, other azole antifungal, or to any of their excipients.
• Known hypersensitivity or inability to receive TMP/SMX or any of its excipients.
• Recent use of an investigational medicinal product within 28 days of the first dose of prophylactic study drug or presence of an investigational device at the time of screening.
• Known infection with HIV.
• Pregnant or lactating females.
• The Principal Investigator (PI) determines that the subject should not participate in the study.
• Considered unlikely to follow up for 90 days after receipt of the BMT due to logistic concerns (i.e., location relative to transplant center).

Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.

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

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

• Men at least 18 years of age referred with clinical suspicion of prostate cancer.
• Serum PSA ≤ 20ng/ml.
• Fit to undergo all procedures listed in protocol.
• Able to provide written informed consent.

• Prior prostate biopsy.
• Prior treatment for prostate cancer.
• Prior prostate MRI on a previous encounter.
• Contraindication to MRI.
• Contraindication to prostate biopsy.
• Unfit to undergo any procedures listed in protocol.

Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.

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

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

• Age ≥ 65 years.
• Diagnosis of MM based on IMWG diagnostic criteria 64.
• Newly diagnosed or have received 1 prior line of treatment.
• Planned to start a new treatment for MM within 30 days.
• Transplant eligible or ineligible.
• Fluent in English (all assessment tools are in English).
• Able to provide written informed consent.

• Received > 1 prior line of treatment.
• Patients included in an interventional therapeutic trial.
• Not able to give informed consent.
• Severe mental or cognitive disorder precluding geriatric assessment.

Eligibility last updated 1/20/22. Questions regarding updates should be directed to the study team contact.

• BMI 18-25 kg/m^2.
• Age > 21 and < 50 years.
• Weight stable for 3 months prior to study entry.
• For females: study days will be scheduled during the follicular phase of their menstrual cycle (i.e., the first 13 days (about 2 weeks) of the cycle).
• Able to provide written informed consent prior to any study procedures and be willing and able to follow study procedures.
• Ability to perform light to moderate physical activity.

• Any contraindication for MRI scanning.
• Any history of childhood (> 95th percentile) or adult obesity (BMI >30 kg/m^2).
• Claustrophobia.
• High intensity training or physical activity.
• Any contraindication for intragastric balloon insertion.
• Any allergies to the study meals.
• Any history of eating disorder.
• Any substance abuse disorder (including alcohol and tobacco).
• Any history of psychiatric disorders.
• Any cardiovascular, endocrine, pulmonary, neurological, or gastrointestinal comorbidities.
• Pregnancy or nursing.
• Any history of bariatric surgery or endoscopic bariatric procedure.
• Use of any medication or supplement that alters appetite.
• Patient has a known history of any condition or factor judged by the investigator to prevent participation in the study or which might hinder study adherence.

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

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

• 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.

• Unaffected first degree relative from Familial Interstitial Pneumonia families (two or more family members with IIP).
• Age at least 40 years old and younger than 75 years old.

• Diagnosed with known (physician-diagnosed) pulmonary fibrosis prior to informed consent.
• Other genetic diseases associated with interstitial lung disease.
• Pregnant women.

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

• 100 subjects > 18 (200 eyes) with visual acuity at any level.

Exclusion Criteria:

• Patients with no ability to sign the consent forms with no LAR.
• Subjects with limited comprehension of English.

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