• Male 7-16 years old
• Diagnosed with DMD, genotypically confirmed
• Stable dose of corticosteroids for at least 24 weeks
• Have intact right and left alternative upper muscle groups
• Mean 6MWT greater than 300m (primary analysis on 300 to 450 meters)
• Stable pulmonary and cardiac function: predicted FVC equal to or greater than 50% and LVEF of greater than 50%
• Previous treatment with drisapersen or any other RNA antisense agent or any gene therapy within the last 6 months
• Participation in any other DMD interventional clinical study within 12 weeks
• Major surgery within 3 months
• Presence of other clinically significant illness
• Major change in the physical therapy regime within 3 months Other inclusion/exclusion criteria apply.

• 1. NMO or NMOSD
• 2. Age 18 to 74 years, inclusive at the time of informed consent.
• 1. Pregnancy or lactation.
• 2. Evidence of other demyelinating disease or PML.
• 3. Known active infection (excluding fungal infections of nail beds or caries dentium) within 4 weeks prior to baseline.

Criteria for Inclusion of Subjects: Hand and forearm amputees: 1. Male or female, age 18 and older, of any race or ethnicity 2. Able and willing to sign Consent 3. Able and willing to participate in all study activities including implantation, testing and explantation of the study device. 4. Able to communicate effectively in English without an interpreter After preliminary screening subjects will be assessed for the following inclusion criteria: 1. Patient has an existing myoelectric hand prosthesis and demonstrates proficiency during daily use 2. Overall and phantom pain are well-controlled and not incapacitating Criteria for Exclusion of Subjects: 1. If MR neurogram and EMG/NCS study show nerve or muscle dysfunction/injury at a higher level than anticipated based on the appearance of the physical amputation stump, the subject may be excluded from the study due to adverse neuromuscular anatomy which would preclude use of the proposed experimental electrode implants. The radiographs will be used to confirm suitability of the amputation stump configuration. If the bony anatomy of the amputation stump is found to be unsuitable, the patient may be excluded from the study. 2. Subjects who have a history of cardiac arrhythmia will be excluded from the study.

• diagnosis of neuroblastoma either by histologic verification and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
• must have high risk neuroblastoma with one of the following: 1) recurrent/progressive disease at any time, 2) refractory disease, 3) persistent disease after at least a partial response to frontline therapy, or 4) Second or greater complete remission after definitive disease progression.
• must have at least one of the following sites of disease: 1) measurable tumor on MRI, CT scan, or X-Ray; 2)MIBG scan with positive uptake in at least one site; 3) bone marrow with tumor cells seen on routine morphology.
• must have an ECOG performance status of 0, 1, or 2
• must have a life expectancy of greater than or equal to 8 weeks
• must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
• hemoglobin greater than or equal to 8.0 (may transfuse to achieve this level)
• ANC greater than or equal to 500 (must be at least 7 days after last dose of growth factor)
• platelet count greater than or equal to 50,000 (must be transfusion independent, defined as at least 1 week since last platelet transfusion)
• age-adjusted serum creatinine less than or equal to 1.5 times normal for age
• normal cardiac function documented by: ejection fraction (greater than or equal to 55%) documented by echocardiogram or radionuclide MUGA evaluation OR fractional shortening (greater than or equal to 27%) documented by echocardiogram AND EKG must demonstrate no abnormality severe enough to justify cardiac medications AND baseline QTc interval greater than or equal to 450 msecs
• total bilirubin less than or equal to 1.5 times normal for age
• ALT and AST less than or equal to 3 times normal for age (for this study, the upper limit of normal of ALT is defined as 45 U/L)
• normal prothrombin time (PT) for age
• baseline hepatitis titers without evidence of acute/active hepatitis. Patients will need to have a negative Hep B Surface Antigen (HBsAg), Hep B e Antigen (HBeAg), Anti-Hep B core Antibody IgM (Anti-HBc IgM), Anti-HAV IgM, and Anti-HCV IgM.
• Patients with CNS parenchymal or meningeal-based lesions are eligible. Patients with prior history of CNS irradiation are study eligible.
• Patients with a seizure disorder are eligible if seizures are controlled on anticonvulsants and if the specific anticonvulsant(s) is not contraindicated.
• Normal lung function as manifested by no dyspnea at rest and no oxygen requirement.
• Due to the potential teratogenic effects of retinoids, negative serum beta-HCG in females, and use of effective contraception in males and females of child-bearing potential, is required.
• skin toxicity no greater than grade 1 per CTCAE v4
• Serum triglycerides < 300mg/dL fasting or on a random plasma test.
• Serum calcium < 11.6mg/dL
• No hematuria and/or proteinuria greater than 1+ on urinalysis.
• Patients with known genetic metabolic conditions, or other ongoing serious medical issues, must be approved by the Study Chair prior to registration.
• Pregnancy or breast feeding. Due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible. Breast milk feeding by study patient is NOT allowed.
• Patients with history of organ and allogeneic stem cell transplantation.
• Patients with a known history of allergy to soy products.
• Patients with a known history of a severe allergy or sensitivity of wheat gluten.
• Patients requiring anti-arrhythmia cardiac medications are NOT eligible.
• Prior therapy with fenretinide, or fenretinide + ketoconazole, if DLT's were experienced.
• A known history of intolerance of ketoconazole.
• Patients on other essential medications for which an interaction with ketoconazole can be expected and for which dose reductions to other essential medications cannot be made in a manner adequate to ensure patient safety.
• Patients who, in the opinion of the investigator, may not be able to comply with safety monitoring requirements of the study.
• Active hepatitis.
• Baseline cardiac QTc interval >450 msecs.
• Eligible for enrollment on other national or regional treatment protocols employing fenretinide/LXS oral power that are reasonably accessible to the patient.
• Patient must NOT receive other anti-cancer agents while on Study.
• Ceftriaxone (Rocephin®) is NOT permitted for 24 hours prior to the start of the oral fenretinide course, during the course, and for 24 hours after the completion of seven day fenretinide course due to concerns of possible adverse effects on the hepatic clearance of fenretinide. Alternative antibiotics should be used. Other cephalosporins are permitted.
• Acetaminophen (Tylenol®) is NOT permitted for 24 hours prior the start of the oral fenretinide course, during the course, and for 48 hours following the completion of the seven day fenretinide course due to concerns of possible hepatic interactions. Ibuprofen (Motrin®) should be used for antipyretic control during this time period.
• Palliative radiation is allowed.
• Patients should NOT receive supplemental Vitamin A, C, or E except as contained in routine total parenteral nutrition vitamin supplements, or in a single daily standard dose oral multivitamin supplement, because of possible interference with antitumor 4-HPR-induced, reactive oxygen species and/or ceramide, and due to the unknown effects of these drugs on retinol levels
• Patients must NOT take any drugs suspected of causing pseudotumor cerebri, which include tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides (Dapsone permitted), lithium, amiodarone, or vitamin A (except as part of routine TPN supplements or as part of a single daily standard dose oral multivitamin supplement).
• Concomitant use of herbal supplements or other alternative therapy medications IS CONTRAINDICATED due to potential adverse metabolic interactions of such supplements with fenretinide.
• Patients should NOT concurrently take medications that may potentially act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein (MDR1) or MRP1 drug/lipid transporters, such as: cyclosporine A or analogue; verapamil; tamoxifen or analogue; chlorpromazine; RU486; indomethacin; or sulfinpyrazone. Patients should NOT concurrently take medications that are known P450 inhibitors. Contact Study Chair if there are questions regarding the suitability of any medication.
• As corticosteroids may impact sphingolipid metabolism, systemic corticosteroids should NOT be used for emesis control during the course of the study. Systemic corticosteroids for asthma control are permissible but should be minimized. Inhaled corticosteroids for asthma control are allowed. Steroids for routine metabolic deficiency states are allowed. Steroids for CNS lesions are allowed.
• Because gastric acidity is necessary for the maximal dissolution and absorption of ketoconazole, when actively taking ketoconazole, patients should avoid/minimize concurrent medications that decrease gastric acid output (such as ranitidine) or increase gastric pH (such as Tums).
• Concomitant medication that may prolong cardiac QT interval, especially those with known interaction with ketoconazole (See Appendices IV, V and VI). A LIST OF THESE MEDICATIONS SHOULD BE PROVIDED TO THE PATIENT AND FAMILY
•PLEASE SEE APPENDICES IV, V and VI FOR A LIST OF MEDICATIONS THAT SHOULD NOT BE USED WITH CONCURRENT KETOCONAZOLE OR THAT SHOULD BE USED WITH CAUTION. Please SEE APPENDIX IV for a partial list of medications potentially prolonging QT interval. Patients may NOT receive therapy with the medications listed as PROHIBITED in Appendix IV and V. Medications in Appendix VI may be used with cautions as noted. Regulatory:
• Patients and/or their parents or legal guardians must sign a written informed consent (or assent.)
• All institutional, FDA, and NCI requirements for human studies must be met.

• Age 1-40 years
• Histologically confirmed malignant extra-cranial solid tumor or demoid fibromatosis
• The subject's tumor must have relapsed after or failed to respond to frontline therapy and there must be no other known curative therapies available. Patients with desmoid fibromatosis must have relapsed after or failed to respond to at least one prior line of therapy, and in the opinion of the treating physician surgical resection of the tumor must not be possible without an amputation or other surgery predicted to result in an unacceptable functional deficit.
• Subject must have a life expectancy of > 8 weeks
• Karnofsky performance status > 50% for patients >16 years of age, or Lansky performance status > 50% for patients < 16 years of age.
• The subject must have at least 1 measurable target lesion >10mm in longest dimension that is in an anatomic location treatable by MR-HIFU. Note that for this study, lesions in bone WILL be considered measurable provided they meet the other criteria by RECIST and are confirmed to be metabolically active on baseline studies by either MIBG uptake (for neuroblastomas) or PET avidity. Target lesions should be located so that they can be adequately heated by a hyperthermia treatment cell with a diameter of up to 58 mm, centered at a depth of 35 to 80 mm from the skin. There should be no staples, implants, extensive scarring, or other highly ultrasound absorbing or reflecting tissue in the expected beam path. For the first 5 patients enrolled on this study only, the lesion must be located in the extremities or pelvis to be considered treatable by MR-HIFU.
• The subject must have recovered from the acute toxic effects of all prior therapy with the exception of alopecia. The following time must have elapsed from the last dose of the following medications to study enrollment:
• myelosuppressive chemotherapy 14 days
• hematopoetic growth factors 7 days (14 days for Neulasta)
• biologic agent 7 days
• monoclonal antibody 3 half-lives
• immunotherapy (ie tumor vaccines) 42 days
• palliative small port XRT 14 days
• substantial bone marrow XRT 6 weeks
• stem cell transplant or infusion without TBI 12 weeks
• total body irradiation (TBI) 24 weeks
• Adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,000/mcL
• platelets ≥ 75,000/mcl (without transfusion for 7 days)
• hemoglobin > 8g/dL (may receive transfusions)
• total bilirubin < 1.5 mg/dL
• ALT(SPGT) < 225 U/L (45 U/L defined as ULN)
• creatinine clearance or radioisotope GFR > 70 mL/min/1.73m2 OR a serum creatinine (mg/dL) less than or equal to the following:
• Age (yrs)-----Male (mg/dL)-----Female (mg/dL)
• 1-1.99----------0.6------------------0.6
• 2-5.99----------0.8------------------0.8
• 6-9.99----------1--------------------1
• 10-12.99------1.2------------------1.2
• 13-15.99------1.5------------------1.4
• >16-------------1.7------------------1.4
• Adequate cardiac function defined as an ejection fraction > 50% or shortening fraction > 27%
• Cumulative lifetime anthracycline dose of < 450mg/m2
• Females and males of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A male of child-bearing potential is any male (regardless of sexual orientation, having undergone a vasectomy, or remaining celibate by choice) who has attained Tanner stage III or greater sexual development. A female of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has undergone menarche OR is > 13 years of age
• Females of child-bearing potential must have a negative serum pregnancy test within 7 days of treatment.
• Signed written informed consent must be obtained prior to any study procedures.
• Subjects may not be receiving any other investigational agents or anticancer therapies.
• Subjects with known active brain metastases will be excluded from this clinical trial. Patients with brain metastases that have been treated and stable for > 30 days following treatment will be eligible.
• Subjects who have received prior Doxil and progressed on this therapy are not eligible, but subjects may have received prior doxorubicin.
• Subjects with a history of tumor progression within 30 days of anthracycline administration are not eligible. However, subjects who have previously received an anthracycline and subsequently relapse greater than 30 days after their most recent prior dose of anthracycline will be eligible.
• History of allergic reactions attributed to doxorubicin or Doxil
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Subjects with a contraindication to MR-HIFU
• Subjects with conditions that carry high anesthetic risk in the opinion of the treating anesthesiologist are not eligible (i.e. subjects with significant airway compression by tumor or craniofacial abnormalities)

Patient witnessed to seize for greater than 5 minute duration prior to treatment with study drug; Patient received adequate dose of benzodiazepines. The last dose of a benzo was administered in the 5-30 minutes prior to study drug administration. The doses may be divided.; continued or recurring seizure in the Emergency Department; Age 2 years or older Known pregnancy; Prisoner; Opt-out identification; Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital or other agents defined in the MoP) for this episode of SE; Treatment with sedatives with anticonvulsant properties other than benzodiazepines (propofol, etomidate, ketamine or other agents defined in the MoP); Endotracheal intubation; Acute traumatic brain injury; Known metabolic disorder; Known liver disease; Known severe renal impairment; Known allergy or other known contraindication to FOS, PHT, LEV, or VPA; Hypoglycemia < 50 mg/dL; Hyperglycemia > 400 mg/dL; Cardiac arrest and post-anoxic seizures

• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment

• Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
• Stable dose of oral corticosteroids for at least 24 weeks
• Intact right and left biceps or 2 alternative upper muscle groups
• Mean 6MWT greater than or equal 300 meters and less than or equal to 450 meters
• Stable pulmonary and cardiac function: forced vital capacity (FVC) equal to or greater than 50% predicted and left ventricular ejection fraction (LVEF) greater than 50%
• Previous treatment with SMT C1100 (BMN-195) at any time
• Treatment with gene therapy at any time
• Previous treatment with PRO045 or PRO053 within 24 weeks prior to Week 1
• Current or previous treatment with any other experimental treatment (other than deflazacort) within 12 weeks prior to Week 1
• Participation in any other DMD interventional clinical study within 12 weeks prior to Week 1
• Major surgery within 3 months prior to Week 1
• Presence of other clinically significant illness
• Major change in physical therapy regimen within 3 months prior to Week 1

1. History of unilateral supratentorial ischemic stroke that occurred at least 9 months but not more than ten 10 years prior to enrollment. 2. Age >22 years and <80 years. 3. FMA-UE score of 20 to 50 (inclusive of 20 and 50). 4. Ability to communicate, understand, and give appropriate consent. Subjects should be able to follow two-step commands. 5. Right- or left-sided weakness of upper extremity. 6. Active wrist flexion/extension; active abduction/extension of thumb and at least two additional digits. 1. History of hemorrhagic stroke 2. Presence of ongoing dysphagia or aspiration difficulties. 3. Subject receiving medication that may significantly interfere with the actions of VNS on neurotransmitter systems at study entry. A list of excluded medications will be provided to Investigators. 4. Prior injury to vagus nerve, either bilateral or unilateral (e.g., injury during carotid endarterectomy). 5. Severe or worse depression (Beck Depression Scale > 29) (Beck et al., 1961) 6. Unfavorable candidacy for device implant surgery (e.g., history of adverse reactions to anesthetics, poor surgical candidate in surgeon's opinion, etc.) 7. Current use of any other stimulation device, such as a pacemaker or other neurostimulator; current use of any other investigational device or drug. 8. Medical or mental instability (diagnosis of personality disorder, psychosis, or substance abuse) that would prevent subject from meeting protocol timeline. 9. Pregnancy or plans to become pregnant or to breastfeed during the study period. 10. Current requirement, or likely future requirement, of diathermy during the study duration. 11. Active rehabilitation within 4 weeks prior to consent. 12. Botox injections or any other non-study active rehabilitation of the upper extremity within 4 weeks prior to therapy through the post-30 day visit (Visit 6). 13. Severe spasticity of the upper limb (Modified Ashworth ≥3) (Bohannon and Smith, 1987). 14. Significant sensory loss. Sensory loss will be measured using the Upper Extremity sensory section of the Fugl Meyer Assessment of Physical Performance. The assessment addresses light touch (2 items) and proprioception (4 items).The highest points attained is 12; subjects with scores less than 6 will be excluded from the study.

• Six or nine months of age and younger (depending on cohort) on day of vector infusion with Type 1 SMA as defined by the following features:
• Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2.
• Onset of disease at birth up to 6 months of age.
• Hypotonia by clinical evaluation with delay in motor skills, poor head control, round shoulder posture and hypermobility of joints.
• Active viral infection (includes HIV or serology positive for hepatitis B or C)
• Use of invasive ventilatory support (tracheotomy with positive pressure)* or pulse oximetry <95% saturation.
• Patients may be put on non-invasive ventilator support (BiPAP) for less than 16 hours a day at the discretion of their physician or research staff.
• Concomitant illness that in the opinion of the PI creates unnecessary risks for gene transfer
• Concomitant use of any of the following drugs: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
• Patients with Anti-AAV9 antibody titers >1:50 as determined by ELISA binding immunoassay.
• Abnormal laboratory values considered clinically significant (GGT > 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 20,000 per cmm) Participation in a recent SMA treatment clinical trial that in the opinion of the PI creates unnecessary risks for gene transfer.
• Family does not want to disclose patient's study participation with primary care physician and other medical providers.
• Patient with signs of aspiration based on a swallowing test and unwilling to use an alternative method to oral feeding.
• Patients with a single base substitution in SMN2 (c.859G>C in exon 7) will be excluded based on predicted mild phenotype.

Inclusion Criteria for Patients:
• African-American or White
• age 65 or greater
• English-speaking
• residing in non-institutional setting
• cognitively able to participate in advance care planning
• Serious or chronic illness including: metastatic cancer; end stage renal disease; advanced liver disease, heart disease or lung disease; amyotrophic lateral sclerosis, severe Parkinson's disease; 2 or more unplanned hospitalizations in the last year; requiring assistance with any basic activity of daily living
• Serious illness based on the following: Clinician answers "no" to the surprise question: "Would you be surprised if this person died in the next 12 months?" Exclusion Criteria for Patients:
• residence in nursing home or assisted living facility
• diagnosis of dementia or unable to consent
• documented advance care plan (living will, health care proxy, MOST form, provider note)
• current or prior use of hospice
• current or prior use of non-hospice palliative care except inpatient palliative care consultation

Key Inclusion Criteria
• Patients up to 60 months (1800 days) of age at time of dosing following diagnostic confirmation during screening period by genotype who demonstrate the ability to sit unassisted for 10 or more seconds but cannot stand or walk
• Diagnostic confirmation by genotype includes lab documentation of homozygous absence of SMN1 exon 7; with exactly three copies of SMN2
• Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
• Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) at < 12 months of age
• Able to sit independently and not standing or walking independently. Definition of sitting independently is defined by the World Health Organization Multicentre Growth Reference Study (WHO-MGRS) criteria of being able to sit up unsupported with head erect for at least 10 seconds. Key Exclusion Criteria
• Current or historical ability to stand or walk independently
• Contraindications for spinal tap procedure or administration of intrathecal therapy (e.g., spina bifida, meningitis, impairment, or clotting abnormalities, or obstructive spinal hardware preventing effective access to cerebrospinal fluid (CSF) space) or presence of an implanted shunt for the drainage of CSF or an implanted central venous (CNS) catheter
• Severe contractures as determined by designated Physical Therapist(s) at screening that interfere with either the ability to attain/demonstrate functional measures (e.g., standing, walking) or interferes with ability to receive intrathecal (IT) dosing
• Severe scoliosis (defined as ≥ 50° curvature of spine) evident on X-ray examination
• Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose administration
• Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening while the patient is awake
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods (i.e., nasogastric tube or nasojejunal tube) or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion

Diagnosed with Parkinson`s disease (consistent with the UK PD Society Brain Bank Criteria for the Diagnosis of PD) Men or women ≥ 30 years old and ≤ 76 years old Female subjects must be either surgically sterilized or 2 years post menopausal at screening Modified Hoehn and Yahr Staging ≤ 3 in the ON state Montreal Cognitive Assessment (MoCA) Score ≥ 26 Currently has a clear and decisive response to levodopa, and receiving a stable dose of levodopa (at least 4 doses per day of levodopa or ≥ 3 doses per day of RytaryTM (Carbidopa and levodopa Extended-Release Capsules) for at least four weeks prior to screening) Experiencing motor fluctuations during waking hours with at least 2 hours of OFF periods each day, including predictable early morning OFF periods, based on subject assessment Able to participate in the study in the practically defined OFF state All anti-parkinsonian medications maintained at a stable dose for at least 4 weeks prior to the initial Screening Visit with the exception of MAO-B inhibitors, which must be maintained at a stable level for at least 8 weeks prior to the screening visit Approved by a central Enrollment Authorization Committee as meeting entry criteria and being a suitable candidate for the study Male subjects agree to use a reliable method of birth control during the study and for at least 90 days following the last dose of BTRX-246040 or placebo. Informed and given ample time and opportunity to think about his/her participation in this study and has given his/her written informed consent on an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved consent form. Judged to be reliable and able to keep all appointments for clinic visits, tests, and procedures, including venipuncture, and examinations required by the protocol. Diagnosis of secondary or an atypical Parkinsonian syndrome Severe disabling dyskinesia Clinically significant psychosis or hallucinations or history of psychosis in past 6 months History of previous neurosurgery for PD Currently or previously on Duopa/Duodopa Currently taking apomorphine Has a diagnosis or history of a substance related disorder per DSM-V criteria (including alcohol but excluding nicotine and caffeine), during the 12 months prior to the Screening Visit. Medical or recreational use of marijuana in the 6 months prior to the Screening Visit Has tested positive at the Screening Visit for drugs of abuse (opiates, cannabinoids, methadone, cocaine, and amphetamines [including ecstasy]) Active suicidal ideation within one year prior to the Screening Visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia- Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 1 year Current major depressive episode or a Beck Depression Inventory-II (BDI-II) score above the protocol-defined threshhold. Subjects receiving treatment for depression with antidepressants may be enrolled if they have been on a stable daily dose for at least 8 weeks before the Screening Visit and are clinically stable in the opinion of the PI Currently or within 8 weeks of screening receiving bupropion Exposure to neuroleptics (antipsychotic drugs) for more than 1 month within the past 2 years, or any exposure within the past year Any malignancy in the 5 years prior to randomization (excluding successfully treated basal cell carcinoma of the skin or cervical carcinoma in situ) Current or previous diagnosis of malignant melanoma or the presence of any suspicious skin lesion based on physical exam findings. Any other clinically significant medical condition or circumstance prior to randomization that, in the opinion of the Investigator, could affect subject safety, preclude evaluation of response, interfere with the ability to comply with study procedures, or prohibit completion of the study (e.g., uncontrolled diabetes mellitus, renal or hepatic impairment, coronary artery disease, evidence of significant active cardiac, respiratory, or hematologic disease, cancer with < 5 year remission (excluding successfully treated basal cell carcinoma of the skin or cervical carcinoma in situ), chronic pain, fibromyalgia or gastric bypass). Prior seizures (other than childhood febrile seizure) or other condition that would place the subject at increased risk of seizures or is taking anticonvulsants for seizure control. History of serious head injury (e.g., skull fracture, cerebral contusion, or trauma resulting in prolonged unconsciousness), intracranial neoplasm or hemorrhage. Orthostatic hypotension that is symptomatic or requires medication Participation in another study of an IMP or medical device currently or in the last 30 days or within 5 half-lives of the IMP (whichever is longer) prior to Screening Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥ 2x upper limit of normal (ULN) or glomerular filtration rate ≤ 60 mL/min at Visit 1 (screening) Nephritic syndrome, end-stage renal disease (and using renal replacement therapy such as hemodialysis or peritoneal dialysis), or a serum creatinine ≥ 2 mg/dL (≥ 172 μmol/L) at the Screening Visit Any other clinically significant abnormalities (i.e., laboratory deviations requiring acute medical intervention or further medical evaluation) in laboratory results at screening including clinical chemistries, hematology, and urinalysis, that, in the judgment of the Investigator, should preclude a subject's participation at study entry. ECG abnormalities at Visit 1 (screening) or Visit 2 that, in the judgment of the Investigator, are clinically significant related to the subject's participation Using the following concomitant medications (contact the Sponsor-designated medical monitor to determine eligibility when in doubt): 1. proton pump inhibitors within 5 half-lives of Screening 2. fluoxetine and irreversible monoamine oxidase inhibitors within 4 weeks of Screening Currently taking or have taken, within 5 half-lives of Screening, any medications or supplements that are strong inhibitors or inducers of CYP3A4. A known hypersensitivity to gelatin capsules. Investigator site personnel directly affiliated with this study, and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. Employees of the Sponsor or of any third-party organizations involved in study who require exclusion of their employees. Have participated in a clinical trial or any other type of medical research judged by the Investigator to be scientifically or medically incompatible with this study within 30 days prior to Visit 1 (screening). Contact the Sponsor-designated medical monitor to determine eligibility when in doubt. Previous completion or withdrawal from this study or any other study investigating BTRX-246040 (previously called LY2940094).

• Patients must be:
• < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
• < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms neuroblastoma/ganglioneuroblastoma
• Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
• Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
• Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
• ?Favorable? genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above
• ?Unfavorable? genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)
• Only patients with MYCN non-amplified tumors are eligible for this study
• Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
• Patients with non-adrenal primaries are eligible, but must have positive uptake on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites (urine or serum) to support the diagnosis of neuroblastoma
• No prior tumor resection or biopsy
• Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
• Group A1:
• > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR
• Patients less than 6 months of age with an adrenal primary tumor > 3.1 and < 5 cm in greatest diameter OR
• < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter
• Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in greatest diameter.
• Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• No life threatening symptoms or no impending neurologic or other organ function compromise (e.g. epidural or intraspinal tumors with existing or impending neurologic impairment, periorbital or calvarial-based lesions with existing or impending cranial nerve impairment, anatomic or mechanical compromise of critical organ function by tumor [abdominal compartment syndrome, urinary obstruction, etc.]); horner syndrome is not considered neurologic compromise
• No prior tumor resection, tumor biopsy ONLY
• Only patients with both favorable histology and favorable genomic features will remain on study as part of Group B; the institution will be notified of histologic and genomic results within 3 weeks of specimen submission on ANBL00B1 or APEC14B1
• Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms neuroblastoma/ganglioneuroblastoma
• No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is allowed
• 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 MYCN amplified tumors are not eligible
• Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
• Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study

1. Subject's parent or legal guardian has provided written informed consent and HIPAA authorization (if applicable) prior to any VBP15-LTE long-term extension study-specific procedures; 2. Subject has previously completed study VBP15-003 up to and including the Week 24 Final assessments, prior to enrolling in the VBP15-LTE study at the conclusion of the VBP15-003 Week 24 Visit [Note: if entering the dose-tapering period, subject is enrolling within 8 weeks after the VBP15‑003 final visit following dose‑tapering]; and 3. Subject and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures. 1. Subject had a serious or severe adverse event in study VBP15-003 that, in the opinion of the Investigator, was probably or definitely related to vamorolone use and precludes safe use of vamorolone for the subject in this long-term extension study; 2. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression; 3. Subject has current or history of chronic systemic fungal or viral infections; 4. Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), mexrenone (mexrenoate potassium) within 4 weeks prior to the first dose of study medication; 5. Subject has evidence of symptomatic cardiomyopathy. [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary]; 6. Subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents [Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 3 months cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical glucocorticoids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration]; 7. Subject has used idebenone within 4 weeks prior to the first dose of study medication; 8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents; 9. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator; 10. Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator 11. Subject is currently taking any investigational drug, or has taken any investigational drug other than vamorolone within 3 months prior to the start of study treatment. Note: Subjects may be re-evaluated if ineligible due to a transient condition which would prevent the subject from participating.

• Women of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration; patients that are pregnant or breast feeding are excluded; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal 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 men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of study; should a woman become pregnant or suspect while she or her partner is participating in this study, she should inform her treating physician immediately
• Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the following criteria:
• Patients must have progressed following at least one line of standard systemic therapy and there must not be other approval/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolong overall survival due to medical issues will be eligible, if other eligibility criteria are met; if the patient is currently receiving therapy, the clinician must have assessed that the current therapy is no longer benefitting the patient prior to enrolling on MATCH, regardless of whether it is considered standard OR
• Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
• NOTE: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage I or II cancer from which the patient is currently in complete remission; any other cancer from which the patient has been disease-free for 5 years
• Patients must have measurable disease
• Patients must meet the criteria below and have received results from one of the designated outside laboratories indicating a "rare variant" that is an actionable Mutation of Interest (aMOI) for specific select subprotocols.
• The following requirements apply:
• The outside laboratory specifically notified the site that patient may be a potential candidate for MATCH due to a detected "rare variant"; the outside lab reports are NOT sufficient for this purpose
• NOTE: The content and format of these specific notifications for the Outside Assay process will vary depending on the designated outside lab in question, as they are each responsible for their own outreach efforts; it is strongly recommended that the designated outside laboratory be contacted to confirm the format and receipt of this notification prior to registering any patients to Step 0
• Patients with an applicable "rare variant" must be able to meet the eligibility criteria for the appropriate subprotocols within 4 weeks following notification of treatment assignment
• NOTE: The receipt of this notification (and the start of the associated deadline for Step 1 registration) may occur shortly after Step 0 registration, since these patients will not be submitting tissue for screening purposes; however, for certain "rare variant" arms, submission of archival tissue for central immunohistochemistry (IHC) testing may be required
• Registration to Step 0 must occur after stopping prior systemic anti-cancer therapy; there is no specific duration for which patients must be off treatment prior to registration to Step 0, as long as all eligibility criteria are met
• There is no particular window of time after notification of potential eligibility from an outside lab in which the patient must be registered to Step 0, but treatment slots will be assigned on a first come, first serve basis to those who do register to Step 0, and are not held for those notified of potential eligibility who do not register to Step 0
• Patients may have received other non-targeted, immunotherapy or targeted treatment between the prior genetic testing at the outside lab and registration to Step 0; the decision to stop such treatment in favor of participation in MATCH, if no further clinical benefit is expected, is per the treating physician's discretion; documentation of a lack of response to the prior treatment is not required in these cases
• NOTE: Other potential aMOIs that would be eligibility criteria for "NON RARE" arms, as determined by the designated laboratories, are not applicable for this process in MATCH
• NOTE: Tumor tissue for the confirmation of "rare variant" by the MATCH assay is to be submitted, preferably from the same time of collection as that evaluated by the designated outside laboratory
• Patient must not require the use of full dose coumarin-derivative anticoagulants such as warfarin; low molecular weight heparin is permitted for prophylactic or therapeutic use; factor X inhibitors are permitted
• NOTE: Warfarin may not be started while enrolled in the EAY131 study
• Stopping the anticoagulation for biopsy should be per site standard operating procedure (SOP)
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 and a life expectancy of at least 3 months
• Patients must not currently be receiving any other investigational agents
• Patients must not have any uncontrolled intercurrent illness including, but not limited to:
• Symptomatic congestive heart failure (New York Heart Association [NYHA] classification of III/IV)
• Unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to registration to Step 0, 2, 4, 6
• Cardiac arrhythmia (ongoing cardiac dysrhythmias of National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4 grade >= 2)
• Psychiatric illness/social situations that would limit compliance with study requirements
• Intra-cardiac defibrillators
• Known cardiac metastases
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (ECHO) (as clinically indicated); (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
• NOTE: To receive an agent, patient must not have any uncontrolled intercurrent illness such as ongoing or active infection; patients with infections unlikely to be resolved within 2 weeks following screening should not be considered for the trial
• Patients must be able to swallow tablets or capsules; a patient with any gastrointestinal disease that would impair ability to swallow, retain, or absorb drug is not eligible
• Patients who are human immunodeficiency virus (HIV)-positive are eligible if:
• CD4+ cell count greater or equal to 250 cells/mm^3
• If patient is on antiretroviral therapy, there must be minimal interactions or overlapping toxicity of the antiretroviral therapy with the experimental cancer treatment; for experimental cancer therapeutics with CYP3A/4 interactions, protease inhibitor therapy is disallowed; suggested regimens to replace protease inhibitor therapy include dolutegravir given with tenofovir/emtricitabine; raltegravir given with tenofovir and emtricitabine; once daily combinations that use pharmacologic boosters may not be used
• No history of non-malignancy acquired immune deficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts
• Probable long-term survival with HIV if cancer were not present
• Any prior therapy, radiotherapy (except palliative radiation therapy of 30 gray [Gy] or less), or major surgery must have been completed >= 4 weeks prior to start of treatment; all adverse events due to prior therapy have resolved to a grade 1 or better (except alopecia and lymphopenia) by start of treatment; palliative radiation therapy must have been completed at least 2 weeks prior to start of treatment; the radiotherapy must not be to a lesion that is included as measurable disease
• NOTE: Prostate cancer patients may continue their luteinizing hormone-releasing hormone (LHRH) agonist
• NOTE: Patients may receive non-protocol treatment after biopsy (if clinically indicated) until they receive notification of results; however, lack of response must be documented prior to registration to Step 1; new non-protocol treatment will NOT be permitted as intervening therapy after registration to Step 0; the decision to stop the intervening non-protocol treatment will be left up to the treating physician if patient has an aMOI; however, patients will need to be off such therapy for at least 4 weeks before receiving any MATCH protocol treatment
• NOTE: For patients entering the study via a designated outside laboratory, no intervening systemic non-protocol treatment is permitted after Step 0 registration; all other eligibility requirements still apply to these patients, including the washouts for prior therapy noted above in this section, the time restrictions outlined, and the eligibility criteria for the intended subprotocol
• Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 4 weeks prior to start of treatment
• Patients must have discontinued steroids >= 1 week prior to registration to Step 0 and remain off steroids thereafter, except as permitted (see below); patients with glioblastoma (GBM) must have been on stable dose of steroids, or be off steroids, for one week prior to registration to treatment (Step 1, 3, 5, 7)
• NOTE: The following steroids are permitted (low dose steroid use is defined as prednisone 10 mg daily or less, or bioequivalent dose of other corticosteroid):
• Temporary steroid use for computed tomography (CT) imaging in setting of contrast allergy
• Low dose steroid use for appetite
• Chronic inhaled steroid use
• Steroid injections for joint disease
• Stable dose of replacement steroid for adrenal insufficiency or low doses for non-malignant disease
• Topical steroid
• Steroids required to manage toxicity related to study treatment, as described in the subprotocols
• Steroids required as pre- or post-chemotherapy medication for acceptable intervening chemotherapy
• NOTE: Steroids must be completed alongside last dose of chemotherapy
• Within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration: Leukocytes >= 3,000/mcL
• Within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration: Absolute neutrophil count >= 1,500/mcL
• Within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration: Platelets >= 100,000/mcL
• NOTE: Patients with documented bone marrow involvement by lymphoma are not required to meet the above hematologic parameters, but must have a platelet count of at least 75,000/mcL and neutrophil count of at least 1,000/mcL
• Within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x institutional ULN is permitted)
• Within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (up to 5 times ULN in presence of liver metastases)
• Within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration: Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to screening step and must meet the following cardiac criteria:
• Resting corrected QT interval (QTc) =< 480 msec
• NOTE: If the first recorded QTc exceeds 480 msec, two additional, consecutive ECGs are required and must result in a mean resting QTc =< 480 msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks between the ECGs
• The following only need to be assessed if the mean QTc > 480 msec
• Check potassium and magnesium serum levels
• Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG to confirm exclusion of patient due to QTc
• For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual read of QTc is required
• For patients with baseline HR < 60 or > 100 bpm, manual read of QT by trained personnel is required, with Fridericia correction applied to determine QTc
• Patient must not have hypokalemia (value < institutional lower limit of normal)
• No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
• NOTE: Patient must be taken off prohibited medication prior to registration to the screening step (Step 0, 2, 4, 6) and remain off these medications thereafter, unless permitted on a subprotocol for the management of treatment related toxicity; patient must be off the drug for at least 5 half-lives prior to registration to the treatment step (Step 1, 3, 5, 7); the medication half-life can be found in the package insert for Food and Drug Administration (FDA) approved drugs

• Diagnosed with neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
• Patients must have high-risk neuroblastoma with at least ONE of the following: 1. Recurrent/progressive disease at any time 2. Refractory disease (i.e. less than a partial response to frontline therapy) 3. Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG, CT/MRI, or bone marrow)
• Patients must have at least ONE of the following sites of disease: 1. Measurable tumor on MRI or CT scan or X-ray 2. MIBG scan with positive uptake at minimum of one site 3. Bone marrow with tumor cells seen on routine morphology
• Patients with a history of complete surgical resection of CNS lesions are eligible if there is no evidence of CNS lesions (MRI or CT required) at study entry evaluation and if other entry criteria are met
• Patients must have a performance status of 0, 1 or 2 (Appendix I). Patients who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have a life expectancy of greater than or equal to 8 weeks
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study 1. Must not have received myelosuppressive chemotherapy and/or biologics within 3 weeks of entry onto this study (4 weeks if prior nitrosourea) 2. Patients must not have received radiation for a minimum of two weeks prior 3. Patients are eligible 12 weeks after autologous stem cell transplant 4. Minimum of six weeks is required following prior therapeutic doses of MIBG. 5. There is no limit on number of prior regimens 6. Must not have received any hematopoietic growth factors within 7 days/ 7. Prior therapy with fenretinide and/or fenretinide + ketoconazole is allowed if no DLT's were experienced. Prior therapy with other retinoids
• Patients must NOT receive other anti-cancer agents while on study
• Palliative radiation is allowed to sites that will not be used to measure response during this study
• All patients must have adequate organ function defined as: 1. Hemoglobin greater than or equal to 8.0 2. ANC greater than or equal to 500 (7 days after last dose of growth factor) 3. Platelet count: greater than or equal to 50,000 at least one week since last platelet transfusion 4. Age-adjusted serum creatinine < 1.5 x normal for age 5. Patient must have normal cardiac function documented by ejection fraction (> 55%) documented by echocardiogram or radionuclide MUGA evaluation or fractional shortening ( > 27%) documented by echocardiogram and EKG must demonstrate no abnormality severe enough to justify cardiac medications and baseline QTc interval less than or equal to 450 msecs 6. Total bilirubin less than or equal to 1.5 x normal for age 7. SGPT (ALT) and SGOT (AST) less than or equal to 3 x normal for age 8. Normal prothrombin time (PT) for age 9. Baseline hepatitis titers without evidence of acute/active hepatitis 10. Serum triglycerides < 300mg/dL fasting or on a random plasma test 11. Serum calcium < 11.6mg/dL 12. No hematuria and/or proteinuria greater than 1+ on urinalysis
• Patients with a seizure disorder are study eligible if seizures are controlled on anticonvulsants
• Normal lung function as manifested by no dyspnea at rest and no oxygen requirement
• Negative serum beta-HCG in females, and use of effective contraception in males and females of child-bearing potential, is required
• Skin toxicity no greater than grade 1
• Patients with known genetic metabolic conditions, or other ongoing serious medical issues, must be approved by the Study Chair prior to registration
• Patients with CNS parenchymal or meningeal-based lesions that are present at study entry evaluation are NOT eligible
• Pregnancy or breast feeding. Due to the potential teratogenic effects of retinoids, pregnant women are NOT eligible. Breast milk feeding by study patient is NOT allowed
• Patients with history of organ and allogeneic stem cell transplantation
• Patients with a known history of allergy to soy products
• Patients with a known history of a severe allergy or sensitivity to wheat gluten
• Patients requiring anti-arrhythmia cardiac medications are NOT eligible
• Prior therapy with fenretinide, or fenretinide + ketoconazole, if DLT's were experienced
• A known history of intolerance to ketoconazole
• A known history of intolerance to vincristine
• Patients on other essential medications for which an interaction with ketoconazole can be expected and for which dose reductions to other essential medications cannot be made in a manner adequate to ensure patient safety
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
• Active hepatitis
• Baseline cardiac QTc interval > 450 msecs

Key
• Signed informed consent of parent or guardian and signed informed assent of participant, if indicated per participant's age and institutional guidelines.
• Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks Key
• Have any condition or worsening condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
• Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
• Participant's parent or legal guardian is not willing or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
• Treatment with another investigational agent, biological agent, or device within one month of Screening, or 5 half-lives of study agent, whichever is longer NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

1. Diagnosis and Age: Ependymoma (WHO grade II) or Anaplastic Ependymoma (WHO grade III) that has relapsed or become refractory to standard therapy. Patients must have had histologic verification of their malignancy at original diagnosis or time of recurrence. Age must be ≥ 2 years and ≤ 21 years of age at study entry. 2. Tumor tissue must be available (from either time of initial diagnosis or relapse) and submitted for central pathology review and correlative biological studies. 3. Performance status: Lansky ≥ 50% for patients ≤ 10 years of age or Karnofsky ≥ 50% for patients > 10 years of age. 4. Adequate bone marrow, liver and renal function. 5. Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x the upper limit of normal. 6. Patients must have measurable residual disease, defined as tumor that is measurable in two diameters on MRI. Diffuse leptomeningeal disease is not considered measurable. 6. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy prior to participating in this trial. No prior myelosuppressive chemotherapy for 28 days prior to study enrollment. Must not have received craniospinal radiation therapy within 24 weeks prior to study entry and no involved field radiation therapy for 12 weeks prior to study enrollment. If patients received prior monoclonal antibody treatment, at least three half-lives must be elapsed by the time of treatment initiation. No investigational drugs for 4 weeks prior to study enrollment. 7. MRI of the brain and the complete spine: All patients must have an MRI of the brain and spine that has measurable tumor (not only diffuse leptomeningeal tumor) within two weeks prior to study enrollment. 1. Prior treatment with Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus). 2. Concommitant use of medications known to have inhibition or induction of CYP3A enzymes. Systemic corticosteroids (e.g., dexamethasone is a CYP3A inducer) are not allowed. Inhaled corticosteroids are allowed. 3. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus. 4. Uncontrolled diabetes mellitus as defined by HbA1c > 8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.

Key
• Genetic documentation of 5q SMA homozygous gene deletion, mutation, or compound heterozygote.
• Onset of clinical signs and symptoms consistent with SMA at ≤6 months of age and have documentation of 3 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at ≤6 months of age, >7 months of age (211 days) at screening, and have documentation of 2 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at >6 months of age, are ≤18 months of age at screening, and have documentation of 2 or 3 SMN2 copies.
• Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures.
• Medical care, such as routine immunizations meets and is expected to continue to meet guidelines set out in the Consensus Statement for Standard of Care in SMA, in the opinion of the Investigator.
• Participants with 2 SMN2 copies must reside within approximately 9 hours' ground-travel distance from a participating study site for the duration of the study. Key
• Meets additional study related criteria.
• Any previous exposure to ISIS 396443; previous dosing in this study or previous studies with ISIS 396443.
• Signs or symptoms of SMA present at birth or within the first week after birth.
• Ventilation for ≥16 hours per day continuously for >21 days at screening.
• Permanent tracheostomy, implanted shunt for CSF drainage, or implanted central nervous system (CNS) catheter at screening.
• History of brain or spinal cord disease that would interfere with the LP procedure, CSF circulation, or safety assessments.
• Hospitalization for surgery (e.g., scoliosis surgery), pulmonary event, or nutritional support within 2 months prior to screening, or hospitalization for surgery planned during the study.
• Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Investigator.
• Treatment with an investigational drug for SMA (e.g., albuterol/salbutamol, riluzole, carnitine, sodium phenylbutyrate, valproate, hydroxyurea), biological agent, or device within 30 days prior to screening. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation. For Part 2 only: To be eligible to participate in Part 2 of this study, participants must meet the following eligibility criteria at the time of consent to participate in Part 2: Participation in Part 1 and completion of the End of Part 1 Evaluation assessments. Ability of parent(s) or legal guardian(s) to understand the purpose and risks of the study and to provide signed and dated informed consent on the Part 2 informed consent form (ICF) and authorization to use confidential health information in accordance with national and local participant privacy regulations. Able to complete all study procedures, measurements, and visits, and parent or legal guardian/participant has adequately supportive psychosocial circumstances, in the opinion of the Investigator. Participants will be excluded from the Part 2 if they meet the following exclusion criterion at the time of consent into Part 2 of the study: Any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in Part 2. The Investigator must reassess the subject's medical fitness for participation and consider any diseases that would preclude treatment. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

• Patient must be newly diagnosed or relapsed/progressed with a brain tumor that has not previously been treated with CRT
• Note: COG therapeutic study participation is not required for ACCL10P1 enrollment
• Patient enrollment must occur within 4 calendar months following completion of CRT
• Reminder: after patient enrollment, baseline testing followed by randomization must occur within 2-4 months after completion of CRT
• The patient must have an identified caregiver who is willing and able to oversee the training practice during the intervention period (ie, for 5-9 weeks starting approximately 3 months after completion of CRT)
• The patient must have access to a telephone and phone number where they can be reached
• The patient and caregiver must have reading, speaking and listening comprehension of English
• All patients and/or their parents or legal guardians must sign a written informed consent (patient assent is also recommended when applicable according to each institution?s policy)
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients with pontine glioma are not eligible
• Patients with an estimated survival of less than one year are not eligible
• Patients with a history of traumatic brain injury prior to tumor diagnosis are not eligible
• Patients with a motor, visual, or auditory handicap that prevents computer use (e.g., unresolved posterior fossa syndrome) are not eligible to participate in this trial
• Patients with full-scale intelligence quotient (IQ) < 70 per previous testing OR existing diagnosis of/educational classification as a student with an intellectual disability are not eligible

• At least 12 years of age
• Written consent/assent by patient and/or legal guardian as per regional and/or IRB requirements
• Non-ambulatory
• Brooke Score for Arms and Shoulders ≤5
• Diagnosis of DMD by medical history and confirmed Duchenne mutation in available genetic testing using a validated genetic test
• Able to perform spirometry
• Able to undergo cardiac and extremity (upper arm) MRI
• Percent predicted FVC between 40 and 90, inclusive
• At least one historical FVC% predicted value within 18 months of baseline
• Left ventricular ejection fraction ≥ 45% as determined by cardiac MRI at screening or within 3 months prior to day 0
• Subjects currently receiving heart failure cardiac medications (e.g. angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a stable regimen for at least 3 months prior to screening
• On a stable dose of corticosteroids for a minimum of 6 months prior to screening with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening and no foreseen change in corticosteroid use during the course of study participation
• Received pneumococcal vaccine and is receiving annual influenza vaccinations
• Adequate renal function: cystatin C ≤1.4 mg/L
• Adequate hematological function 1. Platelets >100,000/mcL 2. Hemoglobin >12 g/dL 3. Absolute neutrophil count >1500/μL
• Adequate hepatic function 1. No history or evidence of liver disease 2. Gamma glutamyl transferase (GGT) ≤3 x upper limit of normal (ULN) 3. Total bilirubin ≤1.5xULN
• If sexually active, will use medically accepted contraceptives during participation in the study and for 3 months after the last dose of study drug
• Requires ≥16 hours continuous ventilation
• Prior or ongoing medical condition that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of 156 weeks of treatment and follow-up would be completed, or could impair the assessment of study results
• Anticipated spine surgery within 156 weeks
• Severe uncontrolled heart disease 1. Need for intravenous diuretics or inotropic support within 3 months prior to screening 2. Hospitalization for a heart failure exacerbation or arrhythmia in last 3 months
• Arrhythmia requiring anti-arrhythmic therapy
• Hospitalization due to respiratory failure in the last 6 weeks
• Poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia
• Known or suspected active hepatitis B or C or history of HIV
• BMI ≥40 kg/m^2 or weight >117 kg
• Exposure to another investigational drug within 28 days prior to start of study treatment
• Exposure to another investigational drug or another approved product for DMD (e.g. eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of the product whichever is longer) prior to first screening visit with the exception of deflazacort. Use of deflazacort if regarded by the principal investigator as standard of care is allowed.

Inclusion criteria: Patients with Pompe disease who previously completed a neoGAA study. The patient and/or their parent/legal guardian is willing and able to provide signed informed consent, and the patient, if <18 years of age, is willing to provide assent if deemed able to do so. The patient (and patient's legal guardian if patient is <18 years of age) must have the ability to comply with the clinical protocol. The patient, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin] at baseline. Exclusion criteria: The patient is concurrently participating in another clinical study using investigational treatment. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study. The patient has clinically significant organic disease (with the exception of symptoms relating to Pompe disease), including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precludes participation in the study or potentially decreases survival. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
• All patients must be in complete remission (CR): 1. No evidence of residual disease on scan 2. No evidence of disease metastatic to bone marrow.
• Specific Criteria by Stratum: Stratum 1: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including: intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;. All subjects on Stratum 1 must have also met the following criteria: • A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to transplant as outlined below: No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy. Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1. Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy. Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).
• Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed:
• Tumor imaging studies including
• Bilateral bone marrow aspirates and biopsy
• This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment.
• Timing from prior therapy: Stratum 1: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy. Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy.
• Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of ≥ 2 months.
• All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below.
• Patients must have adequate organ functions at the time of registration:
• Hematological: Total absolute phagocyte count ≥1000/μL
• Liver: Subjects must have adequate liver function
• Renal: Adequate renal function
• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
• Written informed consent in accordance with institutional and FDA (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).
• BSA (Body Surface Area) of <0.25 m2.
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

1. Male or female between 18 and 85 years old. 2. A wide-neck de novo or non-de novo aneurysm. 3. Appropriate informed consent obtainable as determined by local IRB. 4. Life expectancy > 24 months. 1. Aneurysm rupture within 30 days of enrollment. 2. Bifurcating aneurysms not treatable with coiling. 3. Subject has platelet count of <70,000. 4. Subject has known allergies to nickel-titanium metal. 5. Subject has known allergies to aspirin or heparin. 6. Subject has a life-threatening allergy to contrast (unless treatment for allergy can be tolerated). 7. Subject is currently participating in another clinical research study. 8. Subject is pregnant or breastfeeding. 9. Subject has participated in a drug study within the last 30 days. 10. Subject is unable or unwilling to comply with protocol requirements and obtain required clinical evaluations and follow-up.

• 18 years or older and able to stand (with or without limited assistance)
• Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA or PAF) or NDAN or DBH Deficiency
• Score of at least 4 or greater on Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 (measured at Screening [Visit 1] and the first Titration Visit [Visit 2a] prior to dosing)
• A documented drop of at least 20 millimeters of mercury (mmHg) in SBP, within 3 minutes of standing. This can either be documented in the patient history or assessed during Screening prior to the first Titration Visit (Visit 2a) Additional inclusion criteria for patients taking prescribed droxidopa prior to study entry: Patients who are taking prescribed droxidopa therapy are eligible to participate in the study if they meet the other inclusion criteria and also have been on a stable dose of prescribed droxidopa for at least 2 weeks prior to the Screening Visit (Visit 1). In addition, they must meet either of the following at the Screening Visit (Visit 1):
• The patient's Visit 1 OHSA Item #1 score is ≥ 7 AND the prescribed dose is ≤ 300 mg three times daily (TID); OR
• The patient's Visit 1 OHSA Item #1 score is ≤6 AND worsens by ≥ 2 units when retested after washing out of droxidopa for at least 3 days
• In the investigator's opinion, the patient is not able to understand or cooperate with study procedures
• Known or suspected alcohol or substance use disorder within the past 12 months (DSM-5 criteria)
• Women who are pregnant or breastfeeding
• Women of childbearing potential (WOCP) who are not using at least one method of contraception with their partner
• Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic. Sustained is defined as the average of 3 observations each at least 10 minutes apart with the patient having been supine and at rest for at least 5 minutes prior to each measurement.
• Untreated closed angle glaucoma
• Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study)
• Any significant uncontrolled cardiac arrhythmia
• History of myocardial infarction, within the past 2 years
• Current unstable angina
• Congestive heart failure (NYHA Class 3 or 4)
• Diabetic autonomic neuropathy Additional protocol defined inclusion and exclusion criteria do apply

• PRIOR TO STEP 1 REGISTRATION:
• The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution; WHO grade will be assigned according to WHO 2016 criteria
• Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor; GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings
• Step 1 registration must occur within 180 days of the initial surgery; within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, step 1 registration must occur within 180 days of the initial resection
• For step 1 registration the operating neurosurgeon must provide the modified Simpson grade
• GTR must be confirmed on post-operative imaging following the most recent surgery; submission of both pre-operative and post-operative MRIs is required for patients; if a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained; all sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration; imaging subsequent to enrollment must include pre and post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan and an axial T2 fluid attenuated inversion recovery (FLAIR) sequence; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection; these same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery; computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• If the patient is a primary English speaker, the patient must participate in the NCF and patient reported outcomes part of the study; if the patient is a primary French or Spanish speaker, the patient must participate in the patient reported outcomes part of the study
• NOTE: Central pathology review must occur between steps 1 and 2 of registration; once appropriate pathology specimens are received, central pathology review will occur within 15 days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
• PRIOR TO STEP 2 REGISTRATION:
• Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration
• History/physical examination, including neurologic examination within 60 days prior to step 2 registration
• Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration
• If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception
• Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
• Definitive evidence of metastatic meningioma
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible)
• Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
• Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to:
• Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration
• Transmural myocardial infarction within the last 6 months prior to step 2 registration
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
• Type II neurofibromatosis (NF2)
• Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count < 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to step 2 registration
• Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, etc) or receive gadolinium; note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia
• Pregnancy and/or nursing females

Key
• Advanced solid tumor for which, in the opinion of the Investigator, no other standard therapy offers greater benefit.
• A solid tumor diagnosis in the setting of: 1. a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor 2. a documented NTRK fusion unresponsive to a prior TRK inhibitor 3. a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
• NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV6+ FISH test without identifying NTRK3
• Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 (age ≥16) or Lansky Performance Score (LPS) ≥40% (age<16). If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Status (KPS) (age ≥16) or LPS (age<16) ≥ 50%
• Life expectancy > 4 weeks
• Adequate hematologic, hepatic and renal function.
• Patients with stable CNS primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms and steroid use (if applicable) have been stable for 7 days prior to the first dose of LOXO-195
• Ability to receive study drug orally or by enteral administration Key
• Required treatment with certain strong CYP3A4 inhibitors or inducers.
• Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195 or prolongation of the QT interval corrected (QTcF) > 480 msec within the past 6 months
• Major surgery within 7 days of enrollment
• Uncontrolled systemic bacterial, fungal or viral infection
• Pregnancy or lactation.
• Known hypersensitivity to any of the components of LOXO-195 or Ora-Sweet® SF and OraOlus, for patients receiving liquid suspension

• 18 to 65 years old;
• Interested in reducing/stopping methamphetamine use;
• Speak English;
• Agree to use acceptable birth control (if applicable);
• Be opioid-free at randomization;
• Willing to comply with all study procedures and medication instructions;
• Agree to use a cell phone (or similar study device) to take videos of medication dosing.
• Medical or psychiatric condition which would make participation unsafe;
• Recently participated in a study of pharmacological or behavioral treatment for methamphetamine use disorder;
• Recently taken an investigational drug;
• Prescribed and taken naltrexone or bupropion ≤ 30 days from consent;
• Current or planned extended absence during study period (e.g., jail, surgery, pending legal action);
• Currently pregnant or breastfeeding.

1. Male and female Subjects aged 18 years or older 2. Subjects must have clinical features of HD, which can include motor, cognitive, or behavioral symptoms 3. A confirmatory family history of HD; OR CAG repeat expansion ≥ 37 4. Total Functional Capacity (TFC) score of 5-13 5. Evidence of irritability; a score of at least 2 or greater on the severity measure of either the UHDRS Irritability question (30b) or Aggression question (Disruptive or Aggressive Behavior, 31b) 6. Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) must have a negative pregnancy test, be non-lactating and use adequate contraception methods during the study. Adequate birth control includes: abstinence; oral, implanted or injected contraceptives, e.g., birth control pills; intra-uterine device; barrier (vaginal ring or diaphragm/cervical cap with spermicide); transdermal patch. Reliable contraception must have been in use 30 days prior to the Baseline Visit. Partner(s) contraception (e.g., male partner with vasectomy or other surgical contraception) is acceptable. 7. Men must agree not to father a child during the study and one month after and to use contraception. Barrier with spermicide or surgical contraception is acceptable. Partner(s) contraception (e.g., female partner taking birth control pills or surgically sterile) is acceptable. 8. Subjects must be able to swallow study drug capsules whole. 9. Sufficient English skills to complete all assessments without assistance of an English language interpreter. Subjects with HD who cannot read or write might qualify for enrollment in the study. Site PIs will have to decide in each case whether the Subject can understand and fully participate with help from his/her Informant. 10. Availability of a responsible Informant (referred to as a "study partner" in the consent document) who has good English skills, is familiar with the Subject, and is able and willing to comply with all required study procedures, ensuring that the patient attends all study visits and takes the study medicine as instructed. The study partner must spend time with the patient a minimum of 4 times per week on 4 separate days, and must monitor the patient's compliance and adverse events, participate in caregiver assessments, and use the eDiary. 11. Subject has provided written, informed consent or, if Subject lacks the capacity to provide informed consent (as determined by an independent assessment by a qualified healthcare provider not directly involved in other study activities), a legally authorized representative (LAR) has provided written informed consent and the Subject has provided assent. 1. Any significant neurologic disease other than HD at Screening. 2. Severe psychotic features or other severe psychiatric symptoms within the last three months which could lead to difficulty complying with the protocol. 3. History of active alcohol or substance abuse within the past two years or Subject is unable to refrain from substance abuse throughout the study. 4. Any chronic disability, significant systemic illness or unstable medical condition at Screening or Baseline that could lead to difficulty complying with the protocol. 5. Use of any investigational drugs within 30 days of Screening. 6. Subject has known allergy to any of the components of study medication. 7. Subject is currently pregnant, breast-feeding and/or lactating. 8. Subject acknowledges present use of illicit drugs at Screening.