• Age 2-21 years
• Body weight ≥ 10 kg
• Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
• Must have previously received a systemic chemotherapy
• Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
• HLA-A*02 positive
• Tumor shows MAGE-A4 expression confirmed by central laboratory.
• Performance Status: ECOG 0-1 or Lansky Score ≥ 80
• HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide.
• History of autoimmune or immune mediated disease
• Known central nervous system (CNS) metastases.
• Other prior malignancy that is not considered by the Investigator to be in complete remission
• Clinically significant cardiovascular disease
• Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
• Pregnant or breastfeeding

• Patient must have measurable disease
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of >= 50% or Karnofsky performance status of >= 50%
• Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider
• All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL)
• Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria:
• Patients must have progressed on at least one line of standard systemic therapy OR
• Patients whose disease has no standard treatment that has been shown to prolong overall survival
• Patient must meet one of the following requirements:
• Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR
• Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
• Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial
• Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response [CR] or partial response [PR]) to any intervening therapy after collection of the tissue
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR
• Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
• Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available
• NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only
• NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial

Key
• Participants with stable CF and at least 1 TCR mutation (including F508del) in the CFTR gene Key
• History of solid organ, hematological transplantation, or cancer
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/Exclusion criteria may apply.

Subjects who meet all the following criteria will be included in the study:
• Children of either gender, aged between 6 and 72 months (5 years inclusive).
• Children with recurrent wheezing:
• For ICS/LTRA naïve patients or intermittent users (patients using ICS treatment only during an upper RTI to prevent WE): ≥2 WEs including at least 1 severe episode (i.e., treated with OCS OR having triggered an ED visit/hospitalization), OR ≥3 WEs including at least one that triggered an unscheduled physician visit, in the 12 months prior to enrollment.
• For ICS/LTRA daily users: ≥1 severe WE (i.e., treated with OCS OR having triggered an ED visit/hospitalization) OR ≥2 WEs including at least one that triggered an unscheduled physician visit, as reported by parents or LAR of subject (i.e., guardians), in the 12 months prior to enrollment, while being on their daily controller therapy.
• Up-to-date vaccination status as per applicable State Vaccination Requirements for school/day-care entry.
• Parents or LAR have provided the appropriate written informed consent. Written informed consent must be provided before any study-specific procedures are performed including screening procedures. Note: If a subject is experiencing respiratory symptoms at time of screening, he/she could only be randomized once symptoms have resolved for at least one week.
• Known anatomic alterations of the respiratory tract.
• Wheezing documented to be caused by gastroesophageal reflux.
• Other known chronic respiratory diseases (e.g., tuberculosis or cystic fibrosis).
• Any known autoimmune disease.
• Known human immunodeficiency virus (HIV) infection or any known type of congenital or iatrogenic immune deficiency (including immunoglobulin (Ig) A deficiency).
• Known acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal function abnormalities.
• Children born prematurely i.e., before 34 weeks of gestational age.
• Children with an abnormally low or high weight for their age and height, if this would not allow safe completion of the clinical study in the opinion of the investigator.
• Any known neoplasia or malignancy.
• Treatment with the following medications:
• Systemic (intravenous or intramuscular) or OCS (e.g., oral prednisolone) within 4 weeks before study enrollment.
• Previous and/or concomitant immunosuppressants, immunostimulants, or gamma globulins within 6 months before study enrollment.
• Any major surgery within the last 3 months prior to study enrollment.
• Known allergy or previous intolerance to investigational drug.
• Any other clinical conditions, which in the opinion of the Investigator, would not allow safe completion of the clinical study.
• Other household members have previously been randomized in this clinical study.
• Inability to comply with the study requested visit schedule (e.g., expected relocation within 12 months of the screening for the study).
• Currently enrolled in or has completed any other investigational device or drug study <30 days prior to screening or receiving other investigational agent(s). Note: Subjects with past, present, or at risk of COVID-19 should not be excluded from the study.

Neonate
• Delivered at ≥ 35 weeks of gestation
• <12 hours of age
• Inpatient at Meriter Hospital, Inc. NICU or Newborn Nursery or AFCH PICU or NICU
• Diagnosed as at risk for CoA Neonate
• Major congenital anomalies of the kidney
• Attending physician's discretion to not place sensors due to clinical concerns
• In the researcher's medical opinion, there is a significant likelihood that the neonate would not survive the first 3 days of life Primary Caregiver
• Able to understand and the willing to sign a written informed consent document
• Willing to comply with all study procedures and be available for the duration of the study
• Birth parent (i.e., the parent who gave birth to the baby) who is the primary caregiver of a neonate who is eligible to participate in study
• Agrees to enroll neonate into study
• Aged 15 years or older
• Pregnant mother with a baby diagnosed prenatally as at risk for CoA will be eligible for the study. They must also meet the following criteria:
• Require an "arch watch care plan" as a results of prenatal ultrasonography findings
• Agree to enroll offspring into the study at birth Primary Caregiver
• Subject is unable to provide informed consent, including subjects who are in foster care and subjects within state custody
• Pregnant woman who does not plan to maintain custody of the child after birth, such as instances of adoption or surrogacy Newborn Nursery Nursing Staff:
• All Newborn Nursery nursing staff at Meriter Hospital, Inc.'s Newborn Nursery are eligible to participate

1. History of migraine (with or without aura) for > 6 months before Screening according to the IHS Classification ICHD-319 specifications for pediatric migraine. History may be verified using both medical records and recall by the participant and/or participant's parent(s)/legal representative(s). 2. History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment, with attacks lasting > 3 hours without treatment, and attacks occurring at intervals > 24 hours. 3. Prophylactic migraine medication are permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit, and the dose is not expected to change during the course of the study. 1. Participants may remain on one (1) medication with possible migraine prophylactic effects, excluding CGRP antagonists [biologic or small molecule], during the treatment phases. 2. Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is prohibited. 3. Previously discontinued prophylactic migraine medication must have done so at least 90 days prior to the Screening Visit. 4. Verbally distinguish between migraine and other types of headaches. 5. Participants must have a weight > 40 kg at the Screening Visit. 6. Adequate venous access for blood sampling. 7. Male and female participants ≥ 6 to < 18 years of age (participants must not reach their 18th birthday during the study). 1. History of cluster headache or hemiplegic migraine headache. 2. Confounding and clinically significant pain syndrome that may interfere with the participant's ability to participate in this study. 3. Current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Participants with a lifetime history of psychosis and/or mania. 4. History of suicidal behavior or major psychiatric disorder. 5. Current diagnosis or history of substance abuse; positive drug test at Screening. 6. History of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is likely to affect central nervous system functioning. 7. Recent or planned surgery, requiring general anesthesia, <8 weeks prior to the Screening Visit. 8. Participant has had gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding). 9. Current diagnosis of viral hepatitis or a history of liver disease. 10. Conditions considered clinically relevant in the context of the study such as uncontrolled hypertension (high blood pressure), diabetes, a life-threatening allergy

1. History of migraine (with or without aura) for ≥ 6 months before Screening 2. History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment. 3. 1 or more migraine days requiring treatment during the Observation Phase. 4. Prophylactic migraine medication is permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit 5. Ability to distinguish between migraine and other types of headaches. 6. Weight ≥ 40 kg at the Screening Visit. 7. Adequate venous access for blood sampling. 8. Male and female participants ≥ 6 to < 18 years of age (participants must not reach their 18th birthday before enrollment into the study) 1. History of cluster headache or hemiplegic migraine headache. 2. Confounding and clinically significant pain syndrome 3. Current uncontrolled and/or untreated psychiatric condition for a minimum of 6 months prior to the Screening Visit (lifetime history of psychosis and/or mania are excluded). 4. History of suicidal behavior or major psychiatric disorder. 5. Current diagnosis or history of substance abuse; positive drug test at Screening.

• Enrollment will be fully sequential by age group, with adolescents (12 to less than 18 years old) enrolling before children (6 to less than 12 years old).
• Have severe areata alopecia (AA) for at least 1 year
• Diagnosis for at least 1 year
• Current AA episode of at least 6 months' duration
• SALT score ≥50% at screening and baseline
• History of trial and failure with at least 1 available treatment (topical or other) for AA
• History of psychological counseling related to AA
• Current episode of severe AA of less than 8 years.
• Note: Participants who have severe AA for ≥8 years may be enrolled if episodes of regrowth, spontaneous or under treatment, have been observed on the affected areas over the past 8 years.
• Primarily "diffuse" type of AA (characterized by diffuse hair shedding).
• Are currently experiencing other forms of alopecia including, but not limited to trichotillomania, telogen effluvium, chemotherapy-induced hair loss, or any other concomitant conditions (for example, tinea capitis, psoriasis, lupus erythematosus, or secondary syphilis) that would interfere with evaluations of the effect of study medication on AA.
• Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden
• Have uncontrolled arterial hypertension
• Have had major surgery within 8 weeks prior to screening or will require major surgery during the study
• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking IP or interfere with the interpretation of data.
• Have a positive test for hepatitis B virus (HBV) infection
• Have hepatitis C virus (HCV) infection (positive for anti hepatitis C antibody with confirmed presence of HCV ribonucleic acid [RNA]).
• Have evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies.

Key
• Signed informed consent by study participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the study participant (when applicable)
• Aged 2.5 to <17 years at study entry
• Diagnosis of ACH
• Study participants and parent(s) or LAR(s) are willing and able to comply with study visits and study procedures Key
• Have hypochondroplasia or short stature condition other than ACH (e.g. trisomy 21, pseudoachondroplasia, psychosocial short stature)
• In females, having had their menarche
• Height < -2 or > +2 standard deviations for age and sex based on reference tables on growth in children with ACH
• Annualized height growth velocity ≤1.5 cm/year over a period ≥6 months prior to screening
• Have a concurrent disease or condition that in the view of the Investigator and/or Sponsor, may impact growth or where the treatment is known to impact growth.
• Significant abnormality in screening laboratory results.
• Have been treated with growth hormone, insulin-like growth factor 1 (IGF 1), or anabolic steroids in the previous 6 months or long-term treatment (>3 months) at any time
• Have had regular long-term treatment (>1 month) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable)
• Have had previous guided growth surgery or limb-lengthening surgery within 12 months prior to screening.

• All genders ≥ 6 years of age at Visit 1
• Documentation of a CF diagnosis
• Clinician intent to treat index CF PEx with a planned 14-day course of IV antimicrobials
• At least one documented Pa positive culture within two years prior to Visit 1
• Participant is not pregnant
• No known renal impairment or history of solid organ transplantation
• No IV antimicrobial treatment, ICU admission, pneumothorax, or hemoptysis within 6 weeks prior to Visit 1
• No use of investigational therapies, new CF transmembrane conductance regulator (CFTR) modulators, or treatment for Nontuberculous mycobacteria (NTM) within 4 weeks prior to Visit 1
• No history of hypersensitivity, vestibular, or auditory toxicity with aminoglycosides
• No more than one day of IV aminoglycosides administered for the current PEx treatment prior to Visit 1

To be eligible to participate in the randomized trial, an individual must meet all the following criteria: 1. Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian. 2. Age ≤25 years old at time of randomized trial consent. 3. Confirmed diagnosis of idiopathic SAA, defined as: 1. Bone marrow cellularity <25%, or <30% hematopoietic cells. 2. Two of three of the following (in peripheral blood): neutrophils <0.5 x 10^9/L, platelets <20 x 10^9/L, absolute reticulocyte count <60 x 10^9/L or hemoglobin <8 g/dL. 4. No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing). 5. At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution). 6. In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST. 1. Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children <3). Other testing per center may be performed to exclude IBMFS. 2. Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination. 3. Known severe allergy to ATG. 4. Prior allogeneic or autologous stem cell transplant. 5. Prior solid organ transplant. 6. Infection with human immunodeficiency virus (HIV). 7. Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs). 8. Female patients who are pregnant or breast-feeding. 9. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. 10. Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable

• Participants must have a documented erosive lesion with an Los Angeles (LA) Grade of A to D prior to starting Proton Pump Inhibitor treatment:
• Capable of giving signed informed consent/assent
• Willingness and ability of the participant or parent/legal guardian to complete the eDiary
• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including the use of the eDiary.
• Male and female participants aged 1 to 17 years.
• Minimum body weight 7 kilogram and weight at least at the 5th percentile per the Center for Disease Control standard age and weight chart, for the participant's age.
• To be considered a female of non childbearing potential, the participant must meet at least 1 of the following criteria :
• Premenarchal: The investigator (or other appropriate staff) must discuss the participant's premenarchal status with the participant and parent/legal guardian at office visits and during telephone contacts, as participants who achieve menarche during the study would no longer be considered "female participants of non childbearing potential" and must comply with the protocol requirements applicable to women of childbearing potential.
• Previous administration of an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• Children that may be at high risk from procedural sedation should be carefully evaluated. Participants with a history of complications during prior procedural sedation
• History or presence of upper gastrointestinal anatomic or motor disorders
• Family history of malignant hyperthermia
• Known hypersensitivity to any Proton Pump Inhibitor, including pantoprazole or to any substituted benzimidazole or to any of the excipients.
• Any disorder requiring chronic (daily) use of warfarin, heparin, other anticoagulants, methotrexate, atazanavir or nelfinavir, clopidogrel, or potent inhibitors or inducers of CYP2C19 (eg, phenytoin, sulfamethoxazole, valproic acid, carbamazepine, and griseofulvin).
• Serum creatine kinase levels >3 x upper limit of normal.
• Known history of human immunodeficiency virus or clinical manifestations of acquired immune deficiency syndrome.
• Active malignancy of any type, or history of a malignancy. Participants with a history of malignancies that have been surgically removed or eradicated by irradiation or chemotherapy and who have no evidence of recurrence for at least 5 years before Screening are acceptable.
• Diagnosed as having or has received treatment for esophageal, gastric, pyloric channel, or duodenal ulceration within 30 days before the Screening visit.
• Alanine aminotransferase or blood urea nitrogen >2.0 upper limit of normal or estimated creatinine >1.5 X upper limit of normal for age or any other laboratory abnormality considered by the Investigator to be clinically significant within 14 days before the Baseline Visit (Day 1).
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Has, in the Investigator's opinion, a serious chronic condition (eg, diabetes, epilepsy), which is either not stable or not well controlled and may interfere with the conduct of the study.
• Has any condition possibly affecting drug absorption (eg, gastrectomy). Prior or Concomitant Therapy:
• Frequent, repeated use of oral or parenteral glucocorticoids (eg, prednisone, prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
• Pregnant female participants; breastfeeding female participants.
• Is unwilling or unable to comply with the Lifestyle Considerations section

• Patients must be 5 to 60 years of age at the time of enrollment
• Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]) with stage I or II disease
• Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm)
• Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained
• Pediatric patients (age 5-17 years) must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease. Adult patients must have either a CXR or CT chest
• Patients >= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2
• Patients =< 17 years of age must have a Lansky performance score of >= 50
• Pediatric patients (age 5-17 years): A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• 2 to < 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female)
• 6 to < 10 years (age): 1 mg/dL (male), 1 mg/dL (female)
• 10 to < 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female)
• 13 to < 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• For adult patients (age 18 years or older) (within 7 days prior to enrollment): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
• Total bilirubin =< 2 x upper limit of normal (ULN) (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Aspartate aminotransferase (AST) =< 3 x ULN (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Alanine aminotransferase (ALT) =< 3 x ULN (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Shortening fraction of >= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 7 days prior to enrollment) or ejection fraction of >= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 7 days prior to enrollment)
• Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 7 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of > 92% on room air
• Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with nodular lymphocyte predominant Hodgkin lymphoma
• Patients with a history of active interstitial pneumonitis or interstitial lung disease
• Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients
• Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills
• Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to > 10 mg daily prednisone for patients >= 18 years or > 0.5 mg/kg [up to 10 mg/day] for patients < 18 years) or other immunosuppressive medications within 14 days prior to enrollment
• Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=< 10 mg daily for patients >= 18 years or =< 0.5 mg/kg [up to 10 mg/day] prednisone equivalents) are permitted in the absence of active autoimmune disease
• Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1
• Patients with peripheral neuropathy > grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL
• Prior solid organ transplant
• Prior allogeneic stem cell transplantation
• Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, bacillus calmette guerin [BCG], oral polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment
• Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of < 1% per year when used consistently and correctly) for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer
• Men and women of childbearing potential must continue contraception for a period of 6 months after last dose of brentuximab vedotin
• Women of child-bearing potential (WOCBP) must continue contraception for a period of at least 5 months after the last dose of nivolumab
• 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

1. Participant and/or parent guardian must be able to understand and provide informed consent 2. Children ages 4-12 years of age 3. Cohort 1: Family is self-identified as Plain community member 4. Cohort 2: Madison-area children with parental report of doctor-diagnosed asthma 5. Cohort 3: Madison-area children with no history of asthma by parental report 6. Cohort 4: Madison-area children who have an active respiratory illness 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol 2. Chronic sinusitis (frequent sinus infections) 3. Plans to move out of the area before completing the study 4. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study 5. Enrolled family member

Key
• Participants who reside in areas with endemic Lyme disease and who lead lifestyles that put them at increased risk for Lyme disease. For example, this could include, but not be limited to:
• Individuals who work in B burgdorferi-infected/tick-infested areas, especially those with occupations that may be associated with higher risk of exposure, such as landscaping, forestry, and wildlife and parks management.
• Individuals who pursue recreational activities such as hiking, camping, fishing, hunting, jogging, or gardening in such areas.
• Individuals who live on land plots with tree lines and come into contact with these trees regularly.
• Individuals who have dogs that regularly are outdoors and frequently return with attached ticks.
• Individuals who participate in activities in areas with tall grass, smaller wooded areas beside forests, open fields, lakesides, and riversides. Key
• Any female participants that are pregnant (or have a positive urine pregnancy test) or are breastfeeding.
• Any diagnosis of Lyme disease within the past 3 months.
• Any history of Lyme carditis, neuroborreliosis, or arthritis, or other disseminated Lyme disease regardless of when diagnosed.
• Known tick bite within the past 4 weeks.
• Newly developed or unstable underlying conditions that may interfere with the assessment of Lyme disease, including but not limited to chronic arthralgia/arthritis, second/third-degree AV heart block, chronic pain syndromes, and chronic skin conditions that reduce the ability to detect cutaneous manifestations of Lyme disease.
• Any unstable autoimmune condition with a manifestation (eg, arthritic and neurologic) that may interfere with the assessment of Lyme disease.
• Chronic systemic doxycycline or minocycline or other tetracycline class drug use for acne or any other chronic suppressive antibiotics used to treat other conditions.

• PATIENT INCLUSION CRITERIA FOR ENROLLMENT:
• 6 months to < 22 years at enrollment
• Diagnosed with ALL, AML, or MDS or mixed phenotype acute leukemia (MPAL) for which an allogeneic hematopoietic stem cell transplant is indicated. Complete Remission (CR) status will not be confirmed at the time of enrollment. CR as defined in these sections is required to proceed with the actual HCT treatment plan
• Has not received a prior allogeneic hematopoietic stem cell transplant
• Does not have a suitable human leukocyte antigen (HLA)-matched sibling donor available for stem cell donation
• Has an eligible haploidentical related family donor based on at least intermediate resolution HLA typing
• Patients who also have an eligible 8/8 MUD adult donor based on confirmatory high resolution HLA typing are eligible for randomization to Arm A or Arm B.
• Patients who do not have an eligible MUD donor are eligible for enrollment to Arm C
• 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
• Co-Enrollment on other trials
• Patients will not be excluded from enrollment on this study if already enrolled on other protocols for treatment of high risk and/or relapsed ALL, AML, MPAL and MDS. This is including, but not limited to, COG AAML1831, COG AALL1821, the EndRAD Trial, as well as local institutional trials. We will collect information on all co-enrollments
• Patients will not be excluded from enrollment on this study if receiving immunotherapy prior to transplant as a way to achieve remission and bridge to transplant. This includes chimeric antigen receptor (CAR) T cell therapy and other immunotherapies
• PATIENT INCLUSION CRITERIA TO PROCEED TO HCT:
• Karnofsky Index or Lansky Play-Performance Scale >= 60 on pre-transplant evaluation. Karnofsky scores must be used for patients >= 16 years of age and Lansky scores for patients =< 16 years of age (within 4 weeks of starting therapy)
• A serum creatinine based on age/gender as follows: 6 months to < 1 year: 0.5 mg/dL (Male); 0.5 mg/dL (Female) 1. to < 2 years: 0.6 mg/dL (Male); 0.6 mg/dL (Female) 2. to < 6 years: 0.8 mg/dL (Male); 0.8 mg/dL (Female) 6 to < 10 years: 1 mg/dL (Male); 1 mg/dL (Female) 10 to < 13 years: 1.2 mg/dL (Male); 1.2 mg/dL (Female) 13 to < 16 years: 1.5 mg/dL (Male); 1.4 mg/dL (Female) >= 16 years: 1.7 mg/dL (Male); 1.4 mg/dL (Female)
• OR
• A 24 hour urine Creatinine clearance >= 60 mL/min/1.73 m^2
• OR
• A glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• Serum glutamic-oxaloacetic transaminase (SGOT) aspartate aminotransferase [AST] or serum glutamate pyruvate transaminase (SGPT) aminotransferase [ALT] < 5 x upper limit of normal (ULN) for age
• Total bilirubin < 2.5 mg/dL, unless attributable to Gilbert's Syndrome
• Shortening fraction of >= 27% by echocardiogram or radionuclide scan (MUGA)
• OR
• Ejection fraction of >= 50% by echocardiogram or radionuclide scan (MUGA), choice of test according to local standard of care
• Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and corrected carbon monoxide diffusing capability (DLCO) must all be >= 50% of predicted by pulmonary function tests (PFTs).
• For children who are unable to perform for PFTs (e.g., due to age or developmental delay), the criteria are: no evidence of dyspnea at rest, oxygen (O2) saturation (Sat) > 92% on room air by pulse oximetry, not on supplemental O2 at rest, and not on supplemental O2 at rest
• MPAL in first complete remission (CR1) for whom transplant is indicated. Examples include those patients who are poorly responsive to ALL therapy (end of induction failure( IF-MPAL) to ALL induction (see IF-MPAL note below), end of induction MRD ≥ 5% or end-of-consolidation MRD > 0.01%), as well as patients treated with AML therapy
• IF-MPAL: additional criterion for Induction failure for MPAL ONLY as per ALL1732:
• An increasing number of circulating leukemia cells on 3 or more consecutive CBCs obtained at daily or longer intervals following day 8 of Induction therapy and prior to day 29 with confirmation by flow cytometry OR development of new sites of extramedullary disease, or other laboratory or clinical evidence of refractory disease or progression prior to the end of Induction evaluation (note that residual testicular disease at the end of Induction is an exception)
• MPAL in > second complete remission (CR2)
• ALL high-risk in CR1 for whom transplant is indicated. Examples include: induction failure, treatment failure as per minimal residual disease by flow cytometry > 0.01% after consolidation and not eligible for AALL1721 or AALL1721 not available/unwilling to enroll, hypodiploidy (< 44 chromosomes) with MRD+ > 0.01% after induction, persistent or recurrent cytogenetic or molecular evidence of disease during therapy requiring additional therapy after induction to achieve remission (e.g. persistent molecular BCR-ABL positivity), T cell ALL with persistent MRD > 0.01% after consolidation.
• ALL in CR2 for whom transplant is indicated. Examples include: B-cell: early (=< 36 months from initiation of therapy) bone marrow (BM) relapse, late BM relapse (>= 36 months) with MRD >= 0.1% by flow cytometry after first re-induction therapy; T or B-cell: early (< 18 months) isolated extramedullary (IEM), late (>= 18 months) IEM, end-Block 1 MRD >= 0.1%; T-cell or Philadelphia chromosome positive (Ph+): BM relapse at any time
• ALL in >= third complete remission (CR3)
• Patients treated with chimeric antigen receptor T-cells (CART) cells for whom transplant is indicated. Examples include: transplant for consolidation of CART, loss of CART persistence and/or B cell aplasia < 6 months from infusion or have other evidence (e.g., MRD+) that transplant is indicated to prevent relapse
• AML in CR1 for whom transplant is indicated. Examples include those deemed high risk for relapse as described in AAML1831:
• FLT3/ITD+ with allelic ratio > 0.1 without bZIP CEBPA, NPM1
• FLT3/ITD+ with allelic ratio > 0.1 with concurrent bZIP CEBPA or NPM1 and with evidence of residual AML (MRD >= 0.05%) at end of Induction
• Presence of RAM phenotype or unfavorable prognostic markers (other than FLT3/ITD) per cytogenetics, fluorescence in situ hybridization (FISH), next generation sequencing (NGS) results, regardless of favorable genetic markers, MRD status or FLT3/ITD mutation status
• AML without favorable or unfavorable cytogenetic or molecular features but with evidence of residual AML (MRD >= 0.05%) at end of Induction
• Presence of a non-ITD FLT3 activating mutation and positive MRD (>= 0.05%) at end of Induction 1 regardless of presence of favorable genetic markers.
• AML in >= CR2
• MDS with < 5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation
• Complete remission (CR) is defined as < 5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation with minimum sustained absolute neutrophil count (ANC) of 300 cells/microliter for 1 week or ANC > 500 cells/microliter. We will be collecting data from all approaches to MRD evaluation performed including NGS and polymerase chain reaction (PCR). It is strongly recommended that MPAL be evaluated using multidimensional flow cytometry and/or (KMT2Ar) qt PCR. It is strongly recommended that MPAL be evaluated using multidimensional flow cytometry and/or (KMT2Ar) qt PCR
• DONOR ELIGIBILITY CRITERIA:
• Matched Unrelated Donors: Unrelated donor candidates must be matched at high resolution at a minimum of 8/8 alleles (HLA-A, -B, -C, -DRB1). One-antigen HLA mismatches are not permitted. HLA matching of additional alleles is recommended according to National Marrow Donor Program (NMDP) guidelines, but will be at the discretion of local centers
• Haploidentical Matched Family Members:
• Minimum match level full haploidentical (at least 5/10; HLA-A, -B, -C, -DRB1, -DQB1 alleles). The following issues (in no particular order) should be considered in choosing a haploidentical donor:
• Absent or low patient donor-specific antibodies (DSA)
• Mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be < 2000. Donors with higher levels are not eligible.
• If a screening assay against pooled HLA antigens is used, positive results must be followed with specificity testing using a single antigen assay. The MFI must be < 2000 unless the laboratory has validated higher threshold values for reactivity for HLA antigens (such as HLA-C, -DQ, and -DP), that may be enhanced in concentration on the single antigen assays. Donor anti- recipient antibodies are of unknown clinical significance and do not need to be sent or reported.
• Consult with Study Chair for the clinical significance of any recipient anti-donor HLA antibody.
• If centers are unable to perform this type of testing, please contact the Study Chair to make arrangements for testing.
• If killer immunoglobulin testing (KIR) is performed: KIR status by mismatch, KIR-B, or KIR content criteria can be used according to institutional guidelines.
• ABO compatibility (in order of priority):
• Compatible or minor ABO incompatibility
• Major ABO incompatibility
• CMV serostatus:
• For a CMV seronegative recipient: the priority is to use a CMV seronegative donor when feasible
• For a CMV seropositive recipient: the priority is to use a CMV seropositive donor when feasible
• Age: younger donors including siblings/half-siblings, and second degree relatives (aunts, uncles, cousins) are recommended, even if < 18 years
• Size and vascular access appropriate by center standard for peripheral blood stem cell (PBSC) collection if needed
• Haploidentical matched family members: screened by center health screens and found to be eligible
• Unrelated donors: meet eligibility criteria as defined by the NMDP or other unrelated donor registries. If the donor does not meet the registry eligibility criteria but an acceptable eligibility waiver is completed and signed per registry guidelines, the donor will be considered eligible for this study
• Human immunodeficiency virus (HIV) negative
• Not pregnant
• MUD donors and post-transplant cyclophosphamide haplo donors should be asked to provide BM. If donors refuse and other donors are not available, PBSC is allowed. TCR-alpha beta/CD19 depleted haplo donors must agree to donate PBSC
• Must give informed consent:
• Haploidentical matched family members: Institution standard of care donor consent and Protocol-specific Donor Consent for Optional Studies
• Unrelated donors: standard NMDP Unrelated Donor Consent
• PATIENT EXCLUSION CRITERIA FOR ENROLLMENT:
• Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL/MPAL with known poor outcomes because of sensitivity to alkylator therapy and/or TBI are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc). Patients with Downs syndrome because of increased toxicity with intensive conditioning regimens.
• Patients with any obvious contraindication to myeloablative HCT at the time of enrollment
• Female patients who are pregnant are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• PATIENT EXCLUSION CRITERIA TO PROCEED TO HCT:
• Patients with uncontrolled fungal, bacterial, viral, or parasitic infections are excluded. Patients with history of fungal disease during chemotherapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by computed tomography (CT) evaluation
• Patients with active central nervous system (CNS) leukemia or any other active site of extramedullary disease at the time of initiation of the conditioning regimen are not permitted.
• Note: Those with prior history of CNS or extramedullary disease, but with no active disease at the time of pre-transplant workup, are eligible
• Pregnant or breastfeeding females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants

Key
• Participants who have completed study drug treatment in the parent study (VX21-121-105; NCT Number: NCT05422222) Key
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment, or severe hepatic impairment that might pose an additional risk in administering study drug
• History of solid organ, hematological transplantation, or cancer
• History of drug intolerance in the parent study Other protocol defined Inclusion/Exclusion criteria may apply.

• Written, signed informed consent by the parent(s)/caregiver(s) of the participant, and as required by the institutional review board/human research ethics committee/independent ethics committee (IRB/HREC/IEC).
• Male or female younger than 2 years of age at the time of randomization; or for open label sentinel participants, at the time of first administration of IMP.
• Clinical diagnosis of achondroplasia (ACH) with genetic confirmation of heterozygous genotype present during screening.
• Parent(s)/caregiver(s) willing to follow the protocol and instructions provided, including being able to administer weekly subcutaneous injections of trial treatment.
• Compliance to daily Vitamin D supplementation for infants aged 14 days to 1 year. All participants older than 1 year of age with serum 25-hydroxyvitamin D (25OHD) measured below lower limit of reference range at screening should start daily Vitamin D supplementation prior to randomization.
• Considered eligible based on the medical history, physical examination, and the results of vital signs, ECG, imaging, and clinical laboratory tests performed during the screening period.
• Known or suspected hypersensitivity to the investigational product or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and polyethylene glycol [PEG]).
• Genetic confirmation of ACH homozygous genotype.
• Premature birth with gestational age < 32 weeks.
• Premature birth with gestational age 32 to 37 weeks, unless time from birth is > 6 months at the time of screening and the child is in good nutritional status, defined as gain in body weight expected for age and diagnosis of ACH, as determined by the Investigator and confirmed with the Medical Monitor.
• Anticipated, as assessed by Investigator and confirmed with Medical Monitor, to undergo surgical intervention during trial participation, including cervicomedullary decompression. Evaluation of immediate risk of requiring cervicomedullary decompression surgery will rely on the following assessments:
• Physical examination (e.g., neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins)
• Evidence of uncontrolled sleep apnea as confirmed by local standard of care assessment (e.g. polysomnography or simple sleep test) performed within 6 months prior to screening.
• MRI performed at screening indicating presence of severe cervicomedullary compression (CMC) or spinal cord damage. Presence of abnormal MRI T2 signal intensity at and immediately above and below the cervicomedullary junction should be considered high risk for requiring surgery and the participant is not eligible for trial participation. Common surgeries, such as insertion of grommets, adenoidectomy, tonsillectomy, or myringotomy tube placement are permitted during trial participation.
• Have a growth disorder or medical condition, other than ACH, resulting in short stature or abnormal growth as determined by the Investigator and confirmed with the Medical Monitor.
• Have received any dose of prescription medications and/or investigational medicinal product or device intended to affect stature, growth, or body proportionality (including human growth hormone or vosoritide) at any time.
• Requires or anticipated to require chronic (> 4 weeks) or repeated treatment (more than twice/year) with oral corticosteroids, or high-dose inhaled corticosteroids during trial participation.
• History or presence of injury or disease of the growth plate(s), other than ACH, affecting growth potential of long bones, including Salter-Harris fracture and recent bone-related surgery, as determined by Investigator and confirmed with the Medical Monitor.
• Have a clinically significant finding indicating abnormal cardiac function, including but not limited to:
• Repaired or unrepaired coarctation.
• Moderate or greater complexity congenital heart disease including tetralogy of Fallot, atrioventricular septal defects, truncus arteriosus, total anomalous pulmonary venous return, double outlet right ventricle, or single ventricle heart disease.
• QTcF ≥ 450 msec on screening 12-lead ECG.
• History or presence of a condition impacting hemodynamic stability (such as autonomic dysfunction and orthostatic intolerance).
• History or presence of the following:
• Chronic anemia.
• Chronic renal insufficiency.
• Chronic or recurrent illness that can affect hydration or volume status, including conditions associated with decreased nutritional intake or increased volume loss.
• History or presence of malignant disease.
• Any disease or condition that, in the opinion of the Investigator, may make the participant unlikely to fully complete the trial, not adhering to trial procedures, may confound interpretation of trial results, or may present undue risk from receiving trial treatment. This could include family situations, comorbid conditions, or medications that might impact safety or be considered confounding.