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A Study to Investigate the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Participants With α- or β-Non-Transfusion-Dependent Thalassemia (ENERGIZEKids)
The primary objective of this study is to compare the effect of mitapivat versus placebo on anemia in pediatric participants with alpha- or beta-non-transfusion-dependent thalassemia.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Laurie.Rodgers-Augustyniak@childrens.com
Kathryn Dickerson
ALL
1 Year to 17 Years old
PHASE3
NCT07517133
STU20260644
Inclusion Criteria:
* Written informed consent/assent from the participant (or their legally authorized representative, parent(s), or legal guardian) must be obtained before any study-related procedures are conducted and participants must be willing to comply with all study procedures for the duration of the study.
* Aged 1 to \<18 years and weighing at least 7 kilograms (kg) at the time of providing informed consent/assent.
* Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, hemoglobin E (HbE)/β-thalassemia, or α-thalassemia/hemoglobin H (HbH) disease) based on Hemoglobin (Hb) electrophoresis, Hb high-performance liquid chromatography, and/or DNA analysis from the participant's medical record. If this information is not available from the participant's medical record, the test(s) can be performed by a local laboratory during the Screening Period. If a local laboratory is unable to perform the test(s), results from the comprehensive α- and β-globin genotyping performed by the study central laboratory can be used.
* Hb concentration ≤10.0 grams per deciliter (g/dL) \[100.0 grams per liter (g/L)\], based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.
* Non-transfusion dependent, defined as ≤5 transfusion episodes (also referred to as "transfusion events") during the 24-week period before randomization and no red blood cells (RBC) transfusions ≤8 weeks before providing informed consent/assent and no RBC transfusions during the Screening Period.
* If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization.
* Female participants who have attained menarche must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of informed consent/assent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can include an acceptable barrier method.
Exclusion Criteria:
* Pregnant or breastfeeding.
* Documented history of homozygous or heterozygous hemoglobin S (HbS) or hemoglobin C (HbC).
* Prior exposure to gene therapy or prior bone marrow or stem cell transplantation, including any prior exposure to myeloablative chemotherapy.
* Any conditions other than thalassemia expected to affect sexual maturation.
* Currently receiving treatment with luspatercept; the last dose must have been administered ≥18 weeks before randomization.
* Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 weeks before randomization.
* History of malignancy (active or treated) ≤5 years before providing informed consent/assent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ.
* History of active and/or uncontrolled cardiac or pulmonary disease or clinically relevant QT prolongation within 6 months before providing informed consent/assent.
* Hepatobiliary disorders, including but not limited to:
* Liver disease with histopathological evidence or clinical diagnosis of cirrhosis or severe fibrosis.
* Clinically symptomatic cholelithiasis or cholecystitis (prior cholecystectomy is not exclusionary).
* History of drug-induced cholestatic hepatitis.
* Aspartate Aminotransferase (AST) \>2.5\*Upper Limit of Normal (ULN) (unless due to hemolysis and hepatic iron deposition) and Alanine Transaminase (ALT) \>2.5\*ULN (unless due to hepatic iron deposition).
* Renal dysfunction as defined by an estimated glomerular filtration rate \<60 milliliters per minute (mL/min)/1.73-meter square (m\^2).
* Nonfasting triglycerides \>215 milligrams per deciliter (mg/dL) \[5 millimole per liter (mmol/L)\].
* Active infection requiring systemic antimicrobial therapy at the time of providing informed consent/assent. If antimicrobial therapy is required during the Screening Period, screening procedures should not be performed while antimicrobial therapy is being administered, and the last dose of antimicrobial therapy must be administered ≥7 days before randomization.
* Participants with known active hepatitis B or hepatitis C virus infection.
* Participants with known human immunodeficiency virus (HIV) infection.
* History of major surgery (including splenectomy) ≤16 weeks before providing informed consent/assent and/or a major surgical procedure planned during the study.
* Current enrollment or past participation (within ≤12 weeks or a timeframe equivalent to 5 half-lives of the investigational study drug before administration of the first dose of study drug, whichever is longer) in any other clinical study involving an investigational treatment or device.
* Receiving strong Cytochrome3A4/5 (CYP3A4/5) inhibitors that have not been stopped for ≥5 days or a timeframe equivalent to 5 half-lives (whichever is longer), or strong CYP3A4/5 inducers that have not been stopped for ≥4 weeks or a timeframe equivalent to 5 half-lives (whichever is longer), before randomization.
* Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed; the testosterone dose and preparation must be stable for ≥12 weeks before randomization.
* Known allergy, or other contraindication, to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry filmcoat \[hypromellose, titanium dioxide, lactose monohydrate triacetin, and FD\&C Blue #2\]).
* Any medical, hematological, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:
* Participants who are institutionalized by regulatory or court order.
* Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor). DRUG: Mitapivat, DRUG: Placebo Matching Mitapivat
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Children’s Health
A Study to Assess Adverse Events and How Intravenous (IV) Pivekimab Sunirine Moves Through the Body in Pediatric Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is an aggressive blood cancer, withwith few options for participants who relapse after treatment or who don't respond to treatment. This study will assess the adverse events and how pivekimab sunirine moves through the body in pediatric participants with relapsed or refractory (R/R) AML. Pivekimab sunirine is a drug being evaluated in the treatment of AML. This is an open label, single arm study, participants will be enrolled in 1 of the 3 cohorts based on their age and will receive pivekimab sunirine at a dose based on their weight. Around 18 pediatric participants with a diagnosis of AML will be enrolled in the study at approximately 30 sites around the world. Participants will receive intravenous (IV) pivekimab sunirine alone. The total study duration is approximately 28 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Caroline Smith
ALL
6 Months to 17 Years old
PHASE1
NCT07306832
STU20260749
Inclusion Criteria:
* Must have histologically confirmed acute myeloid leukemia (AML) meeting one of the following disease criteria:
* Second or greater relapse. OR
* Disease refractory to second or subsequent line of therapy (defined as resistant disease after at least one cycle of each treatment regimen).
* Must have myeloid leukemic blasts that are CD123-positive by flow cytometry as determined by the treating institution.
* Has \>= 5% myeloid leukemic blasts in bone marrow at time of relapse or refractory disease and prior to Screening for this study.
* Performance status by Lansky (\< 16 years old at evaluation) or Karnofsky (\>= 16 years old at evaluation) score \>= 50 or ECOG score \<= 2.
* May have status of central nervous system (CNS)1, CNS2, or CNS3 disease without clinical signs or neurologic symptoms suggestive of CNS leukemia, such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome. Participants receiving intrathecal therapy and no additional CNS-directed systemic therapy at study entry are eligible and may continue treatment as clinically indicated in accordance with institutional practice.
* For those participants who have not reached the age of consent, parent or legal guardian with the willingness and ability to provide informed consent and participant willing and able to give assent, as appropriate for age and country.
Exclusion Criteria:
* Known clinically significant cardiac disease.
* Down syndrome.
* Acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML).
* Symptomatic central nervous system (CNS3) disease
* Prior history of any severity veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) of the liver.
* Prior history of hematopoietic stem cell transplant within 6 months prior to Screening without evidence of active GvHD at the time of screening and the participant is off medications to treat or prevent either post-transplant graft-versus-host disease (GvHD) or post-transplant rejection (except for a stable dose of corticosteroids).
* Have received prior Chimeric Antigen Receptor T-cell (CAR-T) therapy.
* Any other known current malignancy requiring therapy.
* Currently receiving anticancer therapy with antineoplastic intent, including radiotherapy, systemic therapy small molecules, monoclonal antibodies, other investigational agents, or high-dose chemotherapy with the exception of intrathecal therapy. DRUG: Pivekimab Sunirine
Acute Myeloid Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
Acute Myeloid Leukemia, Relapsed, Refractory, Pivekimab Sunirine, PVEK, Pediatric
Children’s Health
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B (ATLAS-KIDS)
This is a parallel, Phase 3, two-arm, open-label study to evaluate the efficacy and safety of treatment with fitusiran prophylaxis administered to male pediatric participants (aged 1 to \<12 years) who have severe hemophilia A or B, with or without inhibitory antibodies to FVIII or FIX. Number of participants: Approximately 85 participants will be enrolled into the study: * Approximately 60 fitusiran-naïve participants with severe hemophilia A or B, with or without inhibitors (fitusiran-naïve arm), and * Approximately 25 participants with severe hemophilia A or B with inhibitors rolling over from the EFC15467\* dose confirmation study (roll-over arm). * Fitusiran has been investigated in the pediatric population in study EFC15467, which enrolled male participants aged 1 to \<12 years with hemophilia A or B with inhibitors to examine the safety and tolerability of fitusiran in the pediatric population. Participants will be enrolled into 1 of 2 arms: * Fitusiran-naïve: these participants have not previously received fitusiran, and they will undergo screening and study eligibility assessments. Once enrolled, they will go through a 24-week standard of care (SOC) period before starting fitusiran prophylaxis. * Roll-over participants from the EFC15467 study: only participants who are still on active treatment in study EFC15467 and consenting to study EFC17905 will be eligible to roll over. They will not need to undergo screening or further eligibility assessments. They will directly enroll into the fitusiran treatment period and continue treatment on their current fitusiran dose. The duration of fitusiran treatment will be up to 160 weeks for the fitusiran-naïve arm and up to 60 weeks for the roll-over arm.
Call 214-648-5005
studyfinder@utsouthwestern.edu, susan.corley@childrens.com
Jessica Garcia
MALE
1 Year to 11 Years old
PHASE3
NCT07285460
STU20252266
Inclusion Criteria:
Participants not previously exposed to fitusiran are eligible to be included in the study only if all of the following criteria apply:
* Participant must be 1 to \<12 years of age at the time of enrollment.
* Participants must have severe hemophilia A or B (FVIII \<1% or FIX ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
* Participants must meet inhibitor or non-inhibitor status as defined below:
Inhibitor:
Requiring use of BPA for prophylaxis or BPA as on-demand therapy for any bleeding episodes for at least the last 3 months prior to screening, and meet one of the following Nijmegen-modified Bethesda assay results criteria:
* Inhibitor titer of ≥0.6 BU/mL at screening, OR
* Inhibitor titer of \<0.6 BU/mL at screening with medical record evidence of 2 consecutive titers ≥0.6 BU/mL, OR
* Inhibitor titer of \<0.6 BU/mL at screening with medical record evidence of 1 inhibitor titer ≥0.6 BU/mL and a history of anamnestic response, or severe allergic reaction (eg, anaphylaxis) or nephrotic syndrome
Non-inhibitor:
Requiring use of clotting factor concentrates (CFCs) for prophylaxis or CFCs as on-demand therapy for any bleeding episodes for at least the last 3 months prior to screening, and meet each of the following criterion:
* Nijmegen-modified Bethesda assay inhibitor titer of \<0.6 BU/mL at screening, AND
* No use of BPA to treat bleeding episodes for at least the last 3 months prior to screening
* Participants must have adequate peripheral venous access, as determined by the Investigator, to allow the blood draws required by the study protocol.
* Male: There are no contraceptive requirements for this study except where required by local regulations.
* Capable of giving signed informed consent/assent. A signed written informed consent must be obtained from parent(s)/legal guardian (hereafter referred to as the "parent"), as well as a written or oral assent obtained from participant, per local and national requirements.
Exclusion Criteria:
Participants not previously exposed to fitusiran are excluded from the study if any of the following criteria apply:
* Known co-existing bleeding disorders other than hemophilia A or B.
* Presence of clinically significant liver disease.
* History of antiphospholipid antibody syndrome.
* History of arterial or venous thromboembolism, unrelated to an indwelling venous access
* Any condition (eg, medical concern), which in the opinion of the Investigator, would make the participant unsuitable for dosing or which could interfere with the study compliance, the participant's safety and/or the participant's participation in the completion of the treatment period of the study.
* History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
* Subjects with a central or peripheral indwelling catheter, with a history of venous access complications (such as infections, thrombosis) leading to hospitalization and/or systemic anticoagulation therapy in the last 12 months.
* At screening, anticipated need of surgery during the study or planned surgery scheduled to occur during the study.
* Completion of a surgical procedure within 14 days prior to screening, or currently receiving additional BPA infusion for postoperative hemostasis.
* History of intolerance to SC injection(s).
* Current participation in ITI therapy.
* The use of emicizumab (Hemlibra®) or any non-factor bleed management treatment within 6 months prior to screening
* Prior gene therapy
* Current or future participation in another clinical study, scheduled to occur during this study, involving an investigational product other than fitusiran or an investigational device.
* AT activity \<60% at screening, as determined by central laboratory analysis.
* Co-existing thrombophilic disorder.
* Presence of an active Hepatitis C virus infection
* Presence of acute hepatitis A or Hepatitis E virus infection.
* Presence of acute or chronic hepatitis B virus infection.
* Platelet count ≤100 000/μL.
* Presence of acute infection at screening.
* Human immunodeficiency virus (HIV) positive with a CD4 count of \<400 cells/μL.
* Estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (using the Schwartz formula).
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. DRUG: Fitusiran, BIOLOGICAL: Clotting factor concentrates (CFC) or bypassing agents (BPA), BIOLOGICAL: Antithrombin concentrate (ATIIIC)
Hemophilia
Children’s Health
A Study to Learn More About How Well Finerenone Works, How Safe it is, and How it Moves Into, Through, and Out of the Body Compared to Placebo When Taken With Standard Treatment in Children With Heart Failure and Left Ventricular Systolic Dysfunction (FIORE)
Researchers are looking for a better way to treat children who have heart failure with left ventricular systolic dysfunction (LVSD). Heart failure is a serious condition where the heart is unable to pump enough blood to meet the body's needs. This can lead to symptoms like shortness of breath, fatigue, and poor growth in children. The study treatment, finerenone (also called BAY94-8862), works by blocking a protein involved in inflammation, scarring, and thickening of the heart and blood vessels. This may help the heart to pump blood more effectively. This is the first study to explore its use specifically for children with heart failure and LVSD. The main purpose of this study is to learn if finerenone works to help the heart compared to placebo in children with heart failure and LVSD. For this, the researchers will collect and analyze data on the levels of a protein called NT-proBNP in the blood, which indicates heart stress, and monitor the safety of the treatment. The study will include children with heart failure and LVSD aged from 6 months to less than 18 years. The study participants will be randomly assigned to one of two treatment groups. Based on their group, they will receive either finerenone or a placebo for a duration of 3 months. A placebo looks like a treatment but does not have any medicine in it. Throughout the study, all participants will continue to receive their standard heart failure treatments. At the start of this study, the doctors will check each participant's medical history and current medications. If participants qualify for the treatment phase, they will undergo treatment for about 90 days. During this time, they will visit the study site at least 3 times. During these visits, the participants will: * have their blood pressure, heart rate, temperature, respiratory rate, height and weight measured * have their heart examined by electrocardiogram (ECG) and echocardiogram * have blood samples taken * have physical examinations * answer questions about their medication and whether they have any adverse events, or have their parents or guardians' answers An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments. After the initial three-month study, eligible participants will have the option to join a nine-month open-label extension study where all will receive finerenone. Participants who choose not to enroll in the extension will have a follow-up visit 30 days after their last treatment.
Call 214-648-5005
studyfinder@utsouthwestern.edu, wendy.rojas@childrens.com
Melodie Lynn
ALL
6 Months to 17 Years old
PHASE3
NCT07188805
STU20251927
Inclusion Criteria:
* Participants must be 6 months to \<18 years old at the time when the informed consent/assent is signed.
* Left ventricular systolic dysfunction (LVSD) with left ventricular ejection fraction (LVEF) ≤ 50% at screening assessed by echocardiography.
* Elevated NT-pro BNP levels
* \>500 ng/l for children ≥ 6 months to \< 2 years of age
* \>300 ng/l, for children ≥ 2 years to \<18 years
* Heart failure etiologies including congenital heart defects (CHD) with biventricular physiology and systemic LV; idiopathic cardiomyopathy (CM); familial/inherited and/or genetic CM; history of myocarditis (diagnosis of an acute episode was at least 3 months prior to randomization); neuromuscular disorder (eg, duchenne muscular dystrophy); inborn error of metabolism; mitochondrial disorder; acquired (chemotherapy, iatrogenic, infection, rheumatic, or nutritional); ischemic (eg, Kawasaki disease and postoperative heart failure \[HF\]); LV noncompaction.
* Receiving standard of care (SoC) treatment for heart failure according to local guidelines or investigator´s discretion and being on a stable regimen for 30 days prior to randomization.
* Study participants must have a body weight ≥ 4.0 kg at Visit 1.
Exclusion Criteria:
* Serum potassium:
* \> 5.0 mmol/L for children ≥ 2 years of age at either screening or randomization visit
* \> 5.3 mmol/L for children ≥ 6 months to \< 2 years of age at either screening or randomization visit (if estimated glomerular filtration rate \[eGFR\] \< 60 mL/min/1.73m², threshold of \> 5.0 mmol/L will be used)
* Severe renal dysfunction with eGFR \< 30 ml/min/1.73m² at screening or randomization visit.
* Systolic blood pressure (SBP) \< 5th percentile for age, sex and height at screening or randomization.
* Sustained or symptomatic arrhythmias not controlled by drug or device therapy within 30 days prior to randomization.
* Treatment with a mineralocorticoid receptor antagonist (e.g., spironolactone, eplerenone) within 30 days of randomization.
* Requirement of any intravenous (IV) vasoactive agents, mechanical ventilation, mechanical circulatory support within 30 days prior to randomization.
* Recent surgical procedure or other intervention to correct or palliate CHD within 3 months prior to randomization or anticipated to undergo cardiac surgery during the 3 months after randomization. DRUG: Finerenone (Kerendia, BAY94-8862), DRUG: Placebo
Left Ventricular Systolic Dysfunction, Heart Failure (Pediatric)
Children’s Health
A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy (OPAL)
This double-blind, Phase 2, multiple-dose study will be conducted to evaluate the PK/PD, efficacy, safety, and tolerability of apitegromab in subjects \<2 years old with 5q autosomal recessive SMA who have delayed motor milestones for their age attributed to SMA at the discretion of the Investigator or a Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score \<55.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Samantha.bridges@UTSouthwestern.edu
Kaitlin Batley
ALL
to 2 Years old
PHASE2
NCT07047144
STU20250609
Inclusion Criteria:
• Is \<2 years old at the time of the informed consent
• Had a gestational age of ≥35 weeks and gestational body weight ≥2.0 kg at birth
• Has confirmed diagnosis of 5q autosomal recessive SMA
• Has confirmed presence of SMN2 gene copy(ies)
• Must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam)
• Body weight for age is no less than 1st percentile based on the WHO Child Growth Standards at the Screening Visit
• Has delayed motor milestones for age attributed to SMA at the discretion of the Investigator or a CHOP-INTEND score \<55
Exclusion Criteria:
• Nutritional status that is not anticipated to be stable throughout the study or medical necessity for a gastric feeding tube, where most feeds are administered by this route
• Major orthopedic issues such as severe scoliosis or severe contractures or interventional procedure, including spine or hip surgery, which is considered to have the potential to substantially limit the ability of the subject to be evaluated on any motor function outcome measures, within 6 months before Screening or anticipated during the study
• Any other physical limitations (eg, the subject requires cast for contractures) that would prevent the subject from undergoing motor function outcome measures throughout the study.
DRUG: Apitegromab, DRUG: Nusinersen, DRUG: Risdiplam
Spinal Muscular Atrophy, SMA, Spinal Muscular Atrophy Type 2, Spinal Muscular Atrophy Type 3, Neuromuscular Manifestations, Anti-myostatin
Children’s Health
Resource Intervention to Support Equity (RISE) in High-Risk Neuroblastoma (RISE in HR NBL)
The goal of this study is to test if the addition of a novel income-poverty targeted supportive care intervention (Pediatric Resource Intervention to Support Equity \[Pediatric RISE\]) to usual supportive care for low-income children with high-risk neuroblastoma can improve parent- and child-centered outcomes. Participants will be randomized to receive one of the following for 6-months: * Usual supportive care alone or * Usual supportive care plus Pediatric RISE
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Puja Umaretiya
ALL
to 17 Years old
NA
NCT06831552
STU20251297
Inclusion Criteria:
Patient cohort: The randomized Phase II multi-center RISE intervention will be conducted among a population of poverty-exposed children with high-risk neuroblastoma. Poverty will be a priori defined as parent-reported low-income (\<200% Federal Poverty Level). Children receiving treatment for cancer at study sites will serve as the study cohort, with parents/guardians as survey informants and intervention recipients on behalf of their minor children given that parents (not children) typically manage household finances.
* Patient newly diagnosed with high-risk neuroblastoma
* Patient has established care at study site and initiated cancer-directed therapy
* Patient has not yet initiated Induction Cycle 3
* Patient aged 0-17 years at the time of consent
* Parent/guardian screened positive for self-reported low-income (\<200% Federal Poverty) \*
* Family primary residence in MA, PA, IL, CA, WA, CT, GA, WI and OH
* Both patients co-enrolled on ANBL2131 or those receiving standard of care therapy at their center are eligible to participate
* Patients of all languages are eligible to participate
Exclusion Criteria:
* Foreign national family receiving care as an Embassy-pay patient.
* Child or household member receiving SSI BEHAVIORAL: RISE Intervention
Neuroblastoma, High-Risk Neuroblastoma, Brain and Nervous System
Neuroblastoma, High-risk Neuroblastoma
UT Southwestern; Children’s Health
Digoxin Medulloblastoma Study
The purpose of this study is to evaluate the efficacy of digoxin in treating relapsed non-SHH, non-WNT medulloblastoma in pediatric and young adult patients.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
12 Months to 30 Years old
PHASE2
NCT06701812
STU20250241
Inclusion Criteria:
* Patients must be age \>12 months and \<30 years at the time of enrollment.
* Patients must have relapsed non-WNT, non-SHH medulloblastoma confirmed by a CAP/CLIA certified assay (such as nanostring or methylation) performed on tissue from diagnosis or relapse.
* Patients must have received at least one prior course of chemotherapy for their medulloblastoma. They must also have received irradiation.
* Prior therapy: Therapy may not have been received more recently than the timeframes defined below: Craniospinal radiotherapy: At least 3 months have elapsed since prior craniospinal radiotherapy (at doses ≥ 18 Gy). Local radiotherapy: At least 3 months since prior local radiotherapy to primary tumor. Focal radiotherapy: At least 2 weeks since prior focal radiotherapy to symptomatic metastatic sites. Myelosuppressive chemotherapy and/or immunotherapy and/or biologics: More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas), immunotherapy, or biologics. Hematopoietic growth factor: Seven days must have elapsed since the completion of therapy with colony-stimulating factors (e.g., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], or erythropoietin), or platelet-stimulating agents.
* Patients must have recovered from any surgical procedures such as biopsy, with neurological stability for \> 7 days.
* Patients must have clear residual disease, defined as tumor that is measurable in two perpendicular diameters on MRI (ie, largest tumor diameter and its largest perpendicular). The size of a measurable lesion at baseline should be at least 2 times the thickness of the slices showing the tumor (adding the interslice gap).
* Patients must have a Lansky or Karnofsky performance status score of ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients \< 16 years of age. Patients who are unable to ambulate but who are functional in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
* Patients must have normal organ and marrow function.
* Patient has no evidence of Wolff-Parkinson-White syndrome or high-grade AV block (form of second-degree heart block) on screening ECG.
* Patient has no evidence of hypertrophic obstructive cardiomyopathy on screening echo.
* Any patient that reports recent palpitations (within the last month), or concerning findings on echo or ECG must be evaluated and cleared for treatment with digoxin by a cardiologist prior to enrollment. Study PI should be contacted for additional questions/concerns regarding these patients.
* Patients receiving concurrent dexamethasone are eligible, provided dosage is stable or decreasing for ≥7 days prior to study enrollment.
* Patients must have a stable neurologic status for ≥7 days prior to study enrollment. If a patient experiences neurologic decline following enrollment but prior to day 1 of cycle 1, they should be reassessed for eligibility.
* Pregnancy: Females of childbearing potential must have a negative urine or serum pregnancy test prior to enrollment. Female patients who are lactating must agree to stop breastfeeding.
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.
Exclusion Criteria:
* Participants who are receiving concurrent anticancer or any other investigational agents are ineligible.
* Participants taking digoxin for any reason during treatment for initial diagnosis of medulloblastoma or relapse are ineligible. Exposure to digoxin therapy prior to initial diagnosis of medulloblastoma is allowed.
* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to digoxin are ineligible.
* Patients with serious or inadequately controlled cardiac arrhythmias, including baseline ectopy, ventricular tachycardia, frequent premature ventricular contractions (PVCs), or symptomatic sinus bradycardia are excluded from the study.
* Patients taking medications that are known to interfere with digoxin metabolism are ineligible.
* Participants with uncontrolled intercurrent illness, concurrent clinically significant unrelated systemic illness (e.g. serious infection) or significant cardiac, pulmonary, hepatic, or other organ dysfunction that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results are ineligible.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements are ineligible.
* Pregnant women or women unwilling to stop breastfeeding are excluded from this study because it is unknown how pregnant women with recurrent medulloblastoma will metabolize and tolerate digoxin. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with digoxin in this setting.
* Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study. DRUG: Digoxin
Medulloblastoma, Medulloblastoma, Non-WNT/Non-SHH, Brain and Nervous System
Children’s Health
Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma
This phase III trial tests how well surgery plus chemotherapy compared to surgery alone works in treating patients with type I pleuropulmonary blastoma (PPB), and tests how well surgery plus standard chemotherapy with the addition of topotecan works compared to surgery plus standard chemotherapy alone in treating patients with type II and III PPB. Historically, most children with type I PPB had surgery and approximately 40% of children with type I PPB received chemotherapy following their surgery, usually for 22-42 weeks. There has not been a consistent standard for which children with type I PPB receive chemotherapy after surgery. For patients whose tumor has been removed completely with surgery, observation without chemotherapy may work as well as giving chemotherapy after surgery in preventing a return of the PPB tumor. The standard chemotherapy for patients with types II or III PPB in the United States is four cycles of IVADo (ifosfamide, vincristine, dactinomycin, and doxorubicin) followed by 8 cycles of IVA (ifosfamide, vincristine and dactinomycin). Ifosfamide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Topotecan is in a class of medications called topoisomerase I inhibitors. It works by interfering with tumor cell DNA which kills them. Giving topotecan in addition to standard IVADo and IVA chemotherapy regimens may shrink the cancer as well as or better than the standard therapy or could decrease the chance the tumor spreads while causing fewer side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
to 21 Years old
PHASE3
NCT06647953
STU20250654
Inclusion Criteria:
* 21 years of age or younger
* Newly diagnosed PPB. Note that patients with known germline DICER1 variant or mosaicism with a large, solid unresectable thoracic mass with imaging features characteristic for Type II or III PPB are eligible without histologic confirmation of the diagnosis if a biopsy of the mass is not considered safe or feasible
* Individuals are eligible based on institutional diagnosis of Type I, Ir, II or III PPB diagnosed within 60 days prior to enrollment. Children with Type II or III PPB at risk for clinical decompensation may receive protocol therapy while awaiting rapid central pathology review. Children with Type I or Ir PPB will be assigned to chemotherapy vs. observation based on imaging and central pathology review diagnosis. Type I and Ir patients should not begin chemotherapy prior to return of central pathology results
* For patients with Type II or III PPB (within 7 days prior to enrollment): A serum creatinine based on age/sex as follows:
* Age: 1 month to \< 6 months - Maximum Serum Creatinine (mg/dL): 0.4 (Male), 0.4 (Female)
* Age: 6 months to \< 1 year - Maximum Serum Creatinine (mg/dL): 0.5 (Male), 0.5 (Female)
* Age: 1 to \< 2 years - Maximum Serum Creatinine (mg/dL): 0.6 (Male), 0.6 (Female)
* Age: 2 to \< 6 years - Maximum Serum Creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
* Age: 6 to \< 10 years - Maximum Serum Creatinine (mg/dL): 1 (Male), 1 (Female)
* Age: 10 to \< 13 years - Maximum Serum Creatinine (mg/dL): 1.2 (Male), 1.2 (Female)
* Age: 13 to \< 16 years - Maximum Serum Creatinine (mg/dL): 1.5 (Male), 1.4 (Female)
* Age: ≥ 16 years - Maximum Serum Creatinine (mg/dL): 1.7 (Male), 1.4 (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
* For patients with Type II or III PPB (within 7 days prior to enrollment): Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* For patients with Type II or III PPB (within 7 days prior to enrollment): Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by radionuclide angiogram (within 21 days prior to start of protocol therapy)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4
Exclusion Criteria:
* Administration of prior PPB-directed chemotherapy is an exclusion criterion. Prior treatment for another malignancy is not an exclusion criterion
* Patients with known Charcot-Marie-Tooth disease
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Dexrazoxane, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Ifosfamide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, DRUG: Topotecan, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine
Pleuropulmonary Blastoma, Lung/Thoracic
Children’s Health
Neonatal Platelet Transfusion Threshold Trial (NeoPlaTT)
The objective of the NeoPlaTT trial is to test whether, among extremely preterm infants born at 23 0/7 to 26 6/7 weeks' gestation, a lower platelet transfusion threshold, compared to a higher threshold, improves survival without major or severe bleeding up to 40 0/7 weeks' postmenstrual age (PMA).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Arpineh.Chavez@UTSouthwestern.edu
Vishal Kapadia
ALL
1 Hour to 48 Hours old
NA
NCT06676904
STU20250417
Inclusion Criteria:
* Gestational age of 23 0/7 to 26 6/7 weeks
* Postnatal age of \< 48 hours
Exclusion Criteria:
* Comfort care or withdrawal of care planned
* Neonatal alloimmune thrombocytopenia or suspected/confirmed congenital platelet or bleeding disorder
* Receipt of platelet transfusion
* No receipt of Vitamin K
* Parents/guardian decline consent PROCEDURE: Higher Platelet Transfusion Threshold, PROCEDURE: Lower Platelet Transfusion Threshold
Thrombocytopenia, Neonatal, Platelet Transfusion, Infant, Newborn, Diseases, Infant, Extremely Low Birth Weight, Infant, Small for Gestational Age, Thrombosis
platelet transfusion, neonatal, thrombosis
UT Southwestern; Children’s Health; Parkland Health & Hospital System
A Long-Term Study of JNT-517 in Participants With Phenylketonuria
The goal of this Phase 3, open-label study is to evaluate the long-term safety of JNT-517 in pediatric and adult participants with Phenylketonuria (PKU) after completion of either Study JNT517-101 (NCT05781399) or JNT517-201 (NCT06637514) as well as participants who have not participated in a prior JNT-517 study. In this trial, all participants will receive JNT-517 using age- and weight-banded dosing as outlined in the protocol, regardless of any dose received in a previous study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Juana.Luevano@UTSouthwestern.edu
Markey McNutt
ALL
4 Years to old
PHASE3
NCT06628128
STU20250336
Key
• Diagnosis of phenylketonuria (ie, PAH deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
• Participants 4 years of age and older, inclusive, at time of Screening.
• Not on pegvaliase within 4 weeks of Screening.
• Not on sepiapterin within 2 weeks of Screening.
• If on sapropterin or large neutral amino acids at Screening, must be on a stable dose for 4 weeks prior to Screening.
• Willing and able to maintain a diet consistent in Phe content from the Screening period through the duration of the study, unless otherwise directed by a dietician as allowed in the protocol.
• Body weight ≥ 12.5 kg.
• If female of childbearing potential:
• Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1.
• Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Screening until at least 30 days after the last study drug administration.
• Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
• Is a female not of childbearing potential or postmenopausal, defined as follows:
• Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
• Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing.
• Has not achieved menarche (has not had first menstrual period). If a female achieves menarche during the study, she will need to follow the contraception requirement for females of childbearing potential.
• If male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug. Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
• Capable of giving signed informed consent, or parent/legal guardian to provide informed consent and pediatric participant to give assent, and be able to comply with study procedures.
• Participants with psychiatric illness must be well-controlled for the last 3 months prior to screening visit and, if on medication, on stable medications for the last 3 months. Key
• Participation in this study is not considered safe and/or feasible in the opinion of the Investigator.
• Participants have not completed a previous JNT-517 study and are eligible for another active JNT-517 trial at the site, unless approval is obtained from the medical monitor.
• Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
• Positive for hepatitis B or C or human immunodeficiency virus.
• Any history of significant liver disease.
• Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
• Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
• Estimated glomerular filtration rate \< 60 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) by 2021 Chronic Kidney Disease Epidemiology Collaboration formula (participants aged 17 years or greater) or by Schwartz formula (participants aged 4 to 16 years of age).
• History of drug or alcohol abuse in the last year.
• Use of any medication that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or inhibitors of the transporter P glycoprotein (P-gp) within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration.
• Use of any medications that are a substrate of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, MATE2-K, organic anion transporter 3 (OAT3), or CYP3A4 within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A). CYP3A4 substrates may be allowed if reduction in exposure is not expected to impact safety of the participant after consultation with the Medical Monitor. NOTE: Participants of childbearing potential will be permitted to continue with estrogen- or progesterone based oral contraceptives, but must agree to use 2 other methods of contraception, where at least 1 must be highly effective, or must agree to sexual abstinence during the study.
• Current, recent, or suspected infection within 2 weeks of Screening of Severe Acute Respiratory Syndrome Coronavirus 2/Coronavirus Disease 2019 (SARS-CoV-2/COVID-19).
• Unable to tolerate oral medication or inability to swallow tablets.
• Allergy to JNT-517 or any component of the investigational product.
• Any of the following laboratory values at the Screening visit:
• Alanine aminotransferase or aspartate aminotransferase values ˃ 1.5 x the upper limit of normal (ULN).
• Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin \>4 milligrams per deciliter \[mg/dL\] is exclusionary.
• Hemoglobin ˂10.0 g/dL (˂100.0 grams per liter \[g/L\])
• White blood cell count ˃1 x ULN
• Platelet count ˂150 × 109/L (˂150,000/cubic millimeters\[mm\^3\])
• Participation in another investigational drug trial within 30 days (other than for JNT-517) or, if known 5 half-lives of investigational drug (whichever is longer).
Inclusion Criteria:
• Diagnosis of phenylketonuria (ie, PAH deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
• Participants 4 years of age and older, inclusive, at time of Screening.
• Not on pegvaliase within 4 weeks of Screening.
• Not on sepiapterin within 2 weeks of Screening.
• If on sapropterin or large neutral amino acids at Screening, must be on a stable dose for 4 weeks prior to Screening.
• Willing and able to maintain a diet consistent in Phe content from the Screening period through the duration of the study, unless otherwise directed by a dietician as allowed in the protocol.
• Body weight ≥ 12.5 kg.
• If female of childbearing potential:
• Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1.
• Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Screening until at least 30 days after the last study drug administration.
• Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
• Is a female not of childbearing potential or postmenopausal, defined as follows:
• Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
• Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing.
• Has not achieved menarche (has not had first menstrual period). If a female achieves menarche during the study, she will need to follow the contraception requirement for females of childbearing potential.
• If male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug. Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
• Capable of giving signed informed consent, or parent/legal guardian to provide informed consent and pediatric participant to give assent, and be able to comply with study procedures.
• Participants with psychiatric illness must be well-controlled for the last 3 months prior to screening visit and, if on medication, on stable medications for the last 3 months. Key
Exclusion Criteria:
• Participation in this study is not considered safe and/or feasible in the opinion of the Investigator.
• Participants have not completed a previous JNT-517 study and are eligible for another active JNT-517 trial at the site, unless approval is obtained from the medical monitor.
• Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
• Positive for hepatitis B or C or human immunodeficiency virus.
• Any history of significant liver disease.
• Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
• Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
• Estimated glomerular filtration rate \< 60 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) by 2021 Chronic Kidney Disease Epidemiology Collaboration formula (participants aged 17 years or greater) or by Schwartz formula (participants aged 4 to 16 years of age).
• History of drug or alcohol abuse in the last year.
• Use of any medication that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or inhibitors of the transporter P glycoprotein (P-gp) within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration.
• Use of any medications that are a substrate of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, MATE2-K, organic anion transporter 3 (OAT3), or CYP3A4 within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A). CYP3A4 substrates may be allowed if reduction in exposure is not expected to impact safety of the participant after consultation with the Medical Monitor. NOTE: Participants of childbearing potential will be permitted to continue with estrogen- or progesterone based oral contraceptives, but must agree to use 2 other methods of contraception, where at least 1 must be highly effective, or must agree to sexual abstinence during the study.
• Current, recent, or suspected infection within 2 weeks of Screening of Severe Acute Respiratory Syndrome Coronavirus 2/Coronavirus Disease 2019 (SARS-CoV-2/COVID-19).
• Unable to tolerate oral medication or inability to swallow tablets.
• Allergy to JNT-517 or any component of the investigational product.
• Any of the following laboratory values at the Screening visit:
• Alanine aminotransferase or aspartate aminotransferase values ˃ 1.5 x the upper limit of normal (ULN).
• Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin \>4 milligrams per deciliter \[mg/dL\] is exclusionary.
• Hemoglobin ˂10.0 g/dL (˂100.0 grams per liter \[g/L\])
• White blood cell count ˃1 x ULN
• Platelet count ˂150 × 109/L (˂150,000/cubic millimeters\[mm\^3\])
• Participation in another investigational drug trial within 30 days (other than for JNT-517) or, if known 5 half-lives of investigational drug (whichever is longer).
DRUG: JNT-517
Phenylketonuria (PKU), Other Endocrine System
Phenylketonuria, PKU
UT Southwestern; Children’s Health
A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1 (INSPIRE-NF1)
The trial will be an open label, single arm, phase 2 study to assess the tolerability and efficacy of HLX-1502 in participants with NF1 that are 16 years or older in age with progressive and/or symptomatic PN. This study will also investigate the safety and efficacy of HLX-1502 in a small cohort of 12 to 15 year olds.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Years to old
PHASE2
NCT06541847
STU20251825
Inclusion Criteria:
• All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.
• Participants must have PN(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing significant disfigurement (e.g., orbital lesions), lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Participants with paraspinal PN will be eligible for this trial. Histologic confirmation of tumor is not necessary but should be considered if there are clinical or radiographic findings concerning for malignant transformation of a PN.
• Measurable Disease: Participants must have measurable PN(s) amenable to volumetric MRI analysis. For the purpose of this study, the target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest. Tumors must be at least 3 mL in volume (most PN 3 cm in longest diameter will meet this criteria). If the tumor is \< 3 cm in longest diameter, the participant may still be eligible. Central review of the MRI of the target PN is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis.
• Age: Participants must be ≥ 12 years of age at the time of study entry. Note: Although prior MEKi therapy is not a requirement, patients should be counseled on the availability of FDA-approved MEKi therapies prior to enrollment.
• Weight ≥ 42 kg.
• Performance Level: Participants must have a Lansky (12-15 years of age) or Karnofsky (16+ years of age) score ≥ 50%.
• Organ Function Requirements: Adequate Bone Marrow Function, Adequate Renal Function, Adequate Liver Function, Normal pancreatic function: amylase and lipase levels ≤ 1.5 x ULN. Blood pressure within upper limit of normal as defined below based on the average of the 2nd and 3rd of a total of 3 consecutive measurements, 5 minutes apart. Antihypertensives are permissible to achieve blood pressure within ULN, however must be on stable antihypertensive regimen with no adjustments within 14 days of enrollment.
• Sexually active women of childbearing potential and fertile male participants and their partners must agree to use effective methods of contraception e.g., hormonal oral contraception, injectables, intrauterine device, surgical sterilization including vasectomy, or hormonal implant with barrier methods (male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment. Barrier methods alone are insufficient. True sexual abstinence or evidence of surgical sterility (e.g. vasectomized partner, post-hysterectomy, menopause with last menstrual period \>=12 months prior to screening visit) are acceptable method of birth control. Persons of childbearing potential will be given a pregnancy test within 14 days prior to first dose of study treatment and must have a negative urine or serum pregnancy test.
• The participant is not planning to undergo surgery or other interventions/ treatments for the target lesion, except protocol specified therapy, for the duration of the study.
• The participant or the participant's legal authorized representative is able to understand the informed consent form describing the risks of the study and voluntarily signs the informed consent document.
• In the opinion of the investigator, the participant is willing and able to attend study visits, comply with the study procedures as specified in the protocol, and comply with the administration of the study drug.
Exclusion Criteria:
• Prior treatment with HLX-1502 for a PN.
• The participant has used any of the following systemic medications/ therapies within the specified period prior to enrollment: MEK-inhibitors, other drugs in the TKI class, HLX-1502, Participants may have received treatment for a PN or other tumor/malignancy but must have fully recovered to baseline or CTCAE ≤ Grade 1 from acute toxicities from prior therapies except alopecia, Myelosuppressive chemotherapy, Hematopoietic growth factors, Biologic (anti-neoplastic agent), Investigational Drugs, Any other systemically administered anti-neoplastic agent and Radiation therapy.
• Evidence of an NF1-related tumor such as optic pathway or other low-grade glioma, high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer/tumor requiring treatment with chemotherapy, biologic therapy, surgery or radiation therapy.
• Participants with high-grade glioma, malignant peripheral nerve sheath tumor, or other malignancy who received treatment in the last 12 months. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that have undergone potentially curative therapy. If the investigator has any clinical concerns for ANNUBP/Atypical Neurofibroma or MPNST, a biopsy sample must be taken prior to study confirming eligibility.
• Dental braces or prosthesis that interfere with volumetric analysis of the neurofibroma(s).
• Surgery: Any major surgery within 12 weeks before starting the Treatment Period or foreseen during participation in the trial, any minor surgeries within 1 month before first dose of study treatment and Participants must have complete wound healing from major surgery or minor surgery before the first dose of study treatment. Participants with clinically relevant ongoing complications from prior surgery are not eligible.
• Cataracts noted on ophthalmologic exam.
• Cardiovascular disorders.
• Other clinically significant disorders that would preclude safe study participation, including active infection, a known history of HIV seropositivity or known immunodeficiency or Known history of Hepatitis B or Hepatitis C.
• Participants who require treatment with a drug that is a substrate of CYP1A2, CYP2C8, UGT1A1, UGT1A3 with a narrow therapeutic index during protocol therapy.
• Known severe sensitivity to HLX-1502 or any excipient of HLX-1502 or history of allergic reactions attributed to compounds of similar chemical or biologic composition to HLX-1502.
• Known severe sensitivity to FD\&C Yellow No. 5.
• Participants receiving therapeutic anticoagulation with vitamin K antagonist.
• Participants presently with iron deficiency and/or actively receiving iron replacement or requiring treatment with copper or zinc for any indication at study baseline.
• Pregnant or breast-feeding women.
• Unable or unwilling to swallow tablets.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter ingestion and/or the absorption of HLX-1502.
• Participants who have other medical, social or concurrent challenges that are likely to negatively impact their ability to meet all of the trial obligations and therefore may increase the risk of safe participation in the study.
DRUG: HLX-1502
Neurofibromatosis Type 1, Brain and Nervous System
Neurofibromatosis Type 1, Plexiform Neurofibroma, pediatric
UT Southwestern; Children’s Health
A Culturally-Tailored Mobile Health and Social Media Physical Activity Intervention for Improving Physical Activity in Hispanic or Latino/Latina Adolescent and Young Adult Childhood Cancer Survivors, Walking Juntos Study
This clinical trial tests the impact of a culturally-tailored home-based physical activity program on physical fitness in Hispanic or Latino/Latina adolescent and young adult (AYA) childhood cancer survivors. After treatment for cancer, some AYA survivors experience long-term effects from the cancer and its treatment including weight gain, fatigue and decreased physical fitness. Hispanic or Latino/Latina survivors may have a higher risk of these effects compared to non-Hispanics. Regular physical activity helps maintain healthy weight, energy levels and overall health. Participating in a culturally-tailored home-based physical activity program may help increase physical activity in Hispanic or Latino/Latina AYA childhood cancer survivors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Ksenya Shliakhtsitsava
ALL
15 Years to 20 Years old
PHASE2
NCT06410209
STU-2024-1073
Inclusion Criteria:
* Patient must be ≥ 15 years and \< 21 years at the time of enrollment
* First diagnosis of malignant neoplasm (International Classification of Diseases for Oncology \[ICD-O\] behavior code of "3") in first and continuous remission at the time of enrollment
* Curative cancer treatment must have included chemotherapy (including cellular therapy) and/or radiation (including radioactive iodine). Note: Certain stem cell transplant procedures are excluded. Reminder: Children's Oncology Group (COG) therapeutic trial participation is not required
* Completed all chemotherapy and/or radiation therapy in the last 3-36 months. This includes completion of all oral (e.g., tyrosine kinase inhibitors) and/or maintenance chemotherapy
* Self-report of \< 420 minutes of moderate-to-vigorous physical activity per week as assessed and documented via the study-specific Physical Activity Worksheet. Note: See the case report forms packet on the COG study web page for the study specific Physical Activity Worksheet
* Ambulatory and no known medical contraindications to increasing physical activity
* No known significant physical or cognitive impairment that would prevent use of the electronic devices used for the protocol intervention (e.g., Fitbit, smartphone, tablet, or computer)
* Able to read and write Spanish or English
* Self-identify as Hispanic, Latino/Latina/Latinx
Exclusion Criteria:
* Patients with previous allogeneic hematopoietic stem cell transplant (HSCT) are excluded. Note: Patients with previous autologous HSCT, chimeric antigen receptor T-cell (CAR T-cell) therapy, and other cellular cancer therapies can participate as long as all other eligibility criteria are satisfied
* Post-menarchal female patients who are pregnant or planning to become pregnant in the next year are excluded. Note: Pregnancy status can be established by clinical history with patient. Post-menarchal female patients are eligible as long as they agree to use an effective contraceptive method (including abstinence) during study participation
* Participants who were enrolled in ALTE2031 (Step by Step) cannot enroll in ALTE2321. Participants who were enrolled in ALTE2321 stage 1 (cultural tailoring) cannot enroll to participate in stage 2 (RCT)
* All patients and/or their parents or legal guardians must sign a written informed consent. Note: Informed consent may be obtained electronically/online if allowed by local site policy and institutional review board (IRB)/research ethics board (REB) of record
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met OTHER: Discussion, OTHER: Goal Setting, OTHER: Interview, OTHER: Interview, OTHER: Media Intervention, OTHER: Medical Device Usage and Evaluation, OTHER: Medical Device Usage and Evaluation, OTHER: Questionnaire Administration, OTHER: Reward, OTHER: Text Message-Based Navigation Intervention, OTHER: Text Message-Based Navigation Intervention
Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm, Hodgkins Lymphoma, Leukemia, Not Otherwise Specified, Leukemia, Other, Lymphoid Leukemia, Lymphoma, Multiple Myeloma, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Brain and Nervous System, Breast - Female, Breast - Male, Kidney, Melanoma, skin, Sarcoma
Children’s Health
A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
This phase III trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Arhanti Sadanand
ALL
to 30 Years old
PHASE3
NCT06401330
STU20250865
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and consent to Part A - Eligibility Screening prior to enrollment on AREN2231.
* Patients must be \< 30 years old at enrollment.
* Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor confirmed by central review and with a qualifying Initial Stratum Assignment on APEC14B1-REN.
* Patients must receive a qualifying Initial Stratum Assignment on APEC14B1-REN by Day 14 post-diagnostic procedure (nephrectomy or biopsy), where that procedure is Day 0.
* Patients must enroll on AREN2231 by Day 14.
* Exceptions: If patient reaches Day 14 (post initial diagnostic nephrectomy or biopsy) without receiving an Initial Stratum Assignment on APEC14B1-REN, patient will not be eligible for enrollment on AREN2231 unless all required materials (reports and Case Report Forms and specimens) for an Initial Stratum Assignment arrived by Day 7, but an Initial Stratum Assignment was not completed by Day 14. In these circumstances, after obtaining appropriate protocol consent, the patient may proceed with treatment according to local institutional staging and enroll within 5 calendar days of notification of the central Initial Stratum Assignment being issued, only if the AREN2231 Initial Stratum Assignment is in agreement with any treatment already initiated. If the Initial Stratum Assignment is not in agreement with the local institution's assessment then the patient will be ineligible for AREN2231.
* All sites must have sent or plan to send diagnostic tumor sample for molecular testing through a Clinical Laboratory Improvement Act (CLIA)-certified (or equivalent if outside of the United States \[US\]) laboratory that can detect Loss of Heterozygosity (LOH) of chromosome 1p AND 16q, and gain of chromosome 1q. Patients potentially eligible for mVLR must also have LOH of chromosome 11p15 included.
* Note: Patients are eligible for enrollment prior to obtaining these molecular testing results, and it is strongly recommended that patients are enrolled before these results are available. However, molecular results must be returned and uploaded to APEC14B1-REN for integration into risk stratification by the required timepoints (specific timelines vary by treatment arm). Patients who do not have molecular results available by the arm-specific timepoints may be taken off protocol therapy.
* Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible.
* Note: Lymph node sampling will also be required at delayed nephrectomy. Patients who do not have a lymph node sampled and confirmed as a lymph node by central pathology review at delayed nephrectomy will be taken off protocol therapy.
* Karnofsky performance status must be ≥ 50 for patients \> 16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age.
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR direct bilirubin ≤ 3X ULN for subjects with total bilirubin levels \> 1.5 ULN (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Aspartate aminotransferase (AST/serum glutamate oxaloacetic transaminase \[SGOT\]) OR alanine transaminase (ALT/serum glutamic pyruvate transaminase \[SGPT\]) ≤ 3X ULN OR ≤ 5 X ULN for patients with liver metastases (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% (within 7 days prior to enrollment)
* Note: This criteria only applies to patients centrally classified as Stage IV. Stage II and III patients subsequently assigned to a doxorubicin arm will be off protocol therapy if they do not meet this criteria at time of cardiac function assessment.
* Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* 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.
Exclusion Criteria:
* Patient with a diagnosis of Stage V Bilateral Wilms Tumor.
* Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible.
* Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure.
* Patients with Stage I FHWT with a known or suspected Wilms Tumor predisposition syndrome or condition (contralateral nephrogenic rests and/or unilateral multicentric tumors) are excluded from treatment on the mVLR (Nephrectomy Only) arm.
* Notes:
* In the context of the renal tumor protocols, multicentric tumors and multifocal tumors are equivalent terms, and refer to the occurrence of two or more tumors arising within one kidney.
* Exclusion from the Nephrectomy Only arm applies to two groups of patients:
* Patients \< 4 years with Stage I FHWT other than epithelial subtype AND
* Stage I patients of any age with Epithelial WT
* For the purpose of exclusion from the Nephrectomy Only Arm, known or suspected WT predisposition syndromes or conditions are defined as follows:
* WT Predisposition Syndromes: Beckwith Wiedemann Spectrum, Denys Drash, Trisomy 18, Idiopathic Hemihypertrophy/Isolated Lateralized Overgrowth, WAGR, Simpson-Golabi-Behmel, Bohring-Opitz, or other conditions considered by treating physician to predispose to WT.
* WT Predisposing Conditions:
* A unilateral WT and (radiologic or pathologic) determination of contralateral nephrogenic rest(s) AND/OR
* Unilateral multicentric WT
* Patients treated with partial nephrectomy at initial diagnosis are excluded from mVLR (Nephrectomy Only) arm.
* Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor.
* Please note: Those with lung metastases as the only metastatic site who have complete resection of all radiologically evident lung nodules after enrollment but prior to the lung imaging following Cycle 2 of DD-4A will be inevaluable for lung assessment and subsequent stratum assignment and will, therefore, come off protocol therapy.
* Patients with known Charcot-Marie-Tooth syndrome.
* Patients who have had prior tumor-directed chemotherapy or radiotherapy for the current diagnosis except for therapy delivered for an emergent issue, as medically indicated.
* Patients who will potentially require doxorubicin on this study and have previously received doxorubicin for another diagnosis.
* Patients receiving concurrent chemotherapy for a different diagnosis.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. PROCEDURE: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Nephrectomy, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Stage I Mixed Cell Type Kidney Wilms Tumor, Stage II Mixed Cell Type Kidney Wilms Tumor, Stage III Mixed Cell Type Kidney Wilms Tumor, Stage IV Mixed Cell Type Kidney Wilms Tumor, Kidney
Children’s Health
A Phase 2 Study of Vosoritide in Children With Idiopathic Short Stature
The purpose of this study is to evaluate i) the effect of multiple doses of vosoritide and ii) the effect of the therapeutic dose of vosoritide compared to human growth hormone (hGH)(hGH; only in the United States), in children with idiopathic short stature (ISS).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Daniel.Peter@UTSouthwestern.edu
Nadia Merchant
ALL
3 Years to 11 Years old
PHASE2
NCT06382155
STU-2024-0776
Key
• Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
• If participant is ≥ 5 years at Screening,must be Tanner Stage I to be eligible for enrollment and randomization3. Historic stimulation test result with serum or plasma GH level greater than 10 μg/L or serum IGF-1 in the normal range for age (≥ -1.00 SDs and ≤+2.00 SDs). Key Exclusions:
• Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome), ACAN deficiency.
• Previous treatment with a growth promoting agent
Inclusion Criteria:
• Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
• If participant is ≥ 5 years at Screening,must be Tanner Stage I to be eligible for enrollment and randomization3. Historic stimulation test result with serum or plasma GH level greater than 10 μg/L or serum IGF-1 in the normal range for age (≥ -1.00 SDs and ≤+2.00 SDs). Key Exclusions:
• Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome), ACAN deficiency.
• Previous treatment with a growth promoting agent
DRUG: Vosoritide Injection, DRUG: Human Growth Hormone, DRUG: Placebo
Idiopathic Short Stature
Children’s Health
A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma
This phase II trial studies how well lower dose radiotherapy after chemotherapy (Carboplatin \& Etoposide) works in treating children with central nervous system (CNS) germinomas. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Researchers want to see if lowering the dose of standard radiotherapy (RT) after chemotherapy can help get rid of CNS germinomas with fewer long-term side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
3 Years to 29 Years old
PHASE2
NCT06368817
STU-2024-1003
Inclusion Criteria:
* Patients must be ≥ 3 years and \< 30 years at the time of study enrollment
* Patients must be newly-diagnosed primary localized germinoma of the suprasellar and/or pineal region by pathology and/or serum and/or CSF hCGbeta 5-50 mIU/mL AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists), including tumors with contiguous ventricular or unifocal parenchymal extension. No histologic confirmation required
* Patients with EITHER (A) bifocal (pineal + suprasellar) involvement OR (B) pineal lesion with diabetes insipidus (DI) AND hCGbeta ≤ 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. No histologic confirmation required
* Patients with hCGbeta 51-100 mIU/mL in serum and/or CSF and institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. Histologic confirmation of germinoma IS required
* Patients with germinoma of the basal ganglia and or/thalamic primary sites are eligible
* Patients with metastatic germinoma including non-contiguous disease or distant disease in the brain, ventricles, or spine are eligible
* Patients with germinoma admixed with mature teratoma are eligible
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1-CNS
* Imaging studies must be obtained within 31 days prior to study enrollment and start of protocol therapy. (Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI that must be obtained within 31 days prior to enrollment.)
* Patients must have a cranial magnetic resonance imaging (MRI) with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post-operative brain MRI with and without gadolinium. The post-operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required
* Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment
* Patients must be enrolled, and protocol therapy must begin, no later than 31 days after definitive surgery or clinical diagnosis, whichever is later
* Patients must have eligibility confirmed by Rapid Central Tumor Marker Review performed on APEC14B1-CNS
* Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery. Of note, lumbar CSF should not be performed prior to obtaining spine MRI, as this can make interpretation of the spine MRI less clear
* Patients must have CSF tumor markers obtained prior to study enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first. Ideally serum and CSF tumor markers should be collected at the same time and processed without delay
* For patients with solid tumors: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* For patients with solid tumors: Platelet count \>= 100,000/uL (transfusion independent) (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* For patients with solid tumors: Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* For pediatric patients (age 3-17 years): A serum creatinine based on age/sex as follows (Must be performed within 7 days prior to enrollment unless otherwise indicated):
* Age: 3 to \< 6 years; maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female)
* Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): 1 (male); 1 (female)
* Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
* Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
* Age: ≥ 17 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female) OR a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 OR a glomerular filtration rate (GFR) ≥ 50 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 or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
* For adult patients (age 18 years or older) (Must be performed within 7 days prior to enrollment unless otherwise indicated):
* Creatinine clearance ≥ 70 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 ≤ 1.5 x upper limit of normal (ULN) for age (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* Serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase \[ALT\]) ≤ 135 U/L (Must be performed within 7 days prior to enrollment unless otherwise indicated)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* CNS toxicity =\< grade 2
* Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load are eligible for this study
Exclusion Criteria:
* Patients with any of the following malignant pathological elements are not eligible:
* Endodermal sinus (yolk sac)
* Embryonal carcinoma, choriocarcinoma
* Malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some germinoma)
* Patients with only mature teratoma upon tumor sampling at diagnosis and negative tumor markers are not eligible
* Patients who have received any prior tumor-directed therapy for their diagnosis of germinoma other than surgical intervention and corticosteroids are not eligible
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* 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 RADIATION: 3-Dimensional Conformal Proton Radiation Therapy, RADIATION: 3-Dimensional Conformal Radiation Therapy, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, PROCEDURE: Intensity-Modulated Proton Therapy, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Lumbar Puncture, PROCEDURE: Magnetic Resonance Imaging, OTHER: Questionnaire Administration, PROCEDURE: Surgical Procedure
Basal Ganglia Germinoma, Diabetes Insipidus, Germinoma, Pineal Region Germinoma, Suprasellar Germinoma, Thalamic Germinoma, Brain and Nervous System
Children’s Health
Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma
This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
to 30 Years old
PHASE3
NCT06172296
STU-2024-0471
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131
* ≤ 30 years at the time of initial diagnosis with high-risk disease
* \* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
* Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:
* Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
* Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
* Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy
* Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
* Patients must have a body surface area (BSA) ≥ 0.25 m\^2
* No prior anti-cancer therapy except as outlined below:
* Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent
* Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria
* Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis
* Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* A serum creatinine based on age/sex as follows:
* 1 month to \< 6 months: Male 0.4 mg/dL and female 0.4mg/dL
* 6 months to \< 1 year: Male 0.5 mg/dL and female 0.5 mg/dL
* 1 to \< 2 years: Male 0.6 mg/dL and female 0.6 mg/dL
* 2 to \< 6 years: Male 0.8 mg/dL and female 0.8 mg/dL
* 6 to \< 10 years: Male 1 mg/dL and female 1 mg/dL
* 10 to \< 13 years: Male 1.2 mg/dL and female 1.2 mg/dL
* 13 to \< 16 years: Male 1.5 mg/dL and female 1.4 mg/dL
* ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL
* The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC)
* or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 or
* or a GFR ≥ 70 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
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase \[ALT\]) ≤ 10 x ULN\*
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* \* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
* Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection:
No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Exclusion Criteria:
* Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features
* Patients ≥ 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features
* Patients with known bone marrow failure syndromes
* Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable
* Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required prior to enrollment for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dinutuximab, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Etoposide, PROCEDURE: FDG-Positron Emission Tomography and Computed Tomography Scan, PROCEDURE: Hematopoietic Cell Transplantation, DRUG: Irinotecan, DRUG: Isotretinoin, PROCEDURE: Leukapheresis, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan, PROCEDURE: Multigated Acquisition Scan, RADIATION: Radiation Therapy, PROCEDURE: Radionuclide Imaging, OTHER: Survey Administration, DRUG: Temozolomide, DRUG: Thiotepa, DRUG: Topotecan, PROCEDURE: Tumor Resection, DRUG: Vincristine
Ganglioneuroblastoma, Nodular, Neuroblastoma, Brain and Nervous System
Children’s Health
Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia
This is a research study to find out if adding a new study drug called revumenib to commonly used chemotherapy drugs is safe and if they have beneficial effects in treating patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that did not go into remission after treatment (refractory) or has come back after treatment (relapsed), and to determine the total dose of the 3-drug combination of revumenib, azacitidine and venetoclax that can be given safely in participants also taking an anti-fungal drug. Primary Objective * To determine the safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL. Secondary Objectives * Describe the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and overall survival for patients treated with revumenib + azacitidine + venetoclax at the recommended phase 2 dose (RP2D).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
1 Year to 30 Years old
PHASE1
NCT06177067
STU-2024-0647
Inclusion Criteria:
Participants must have a diagnosis of AML or ALAL and meet the criteria below:
* Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy (one course for secondary AML), or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry.
However, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.
* Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A rearrangement (KAT6Ar), or SET::NUP214
* Adequate organ function, defined as total bilirubin \< 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \<3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL/min/1.73 m\^2, and left ventricular ejection fraction ≥ 40%
* QTcF \< 480 msec (average of triplicate)
* Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.
* Lansky ≥ 60 for patients who are \< 16 years old and Karnofsky ≥ 60% for patients who are \> 16 years old.
* At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m\^2/day). In addition, all toxicities must have resolved to grade 1 or less.
* Patients must have a leukocyte count \<25,000 cells/uL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.
* For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..
* Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.
* Patients of reproductive potential must agree to use effective contraception for the duration of study participation.
Patients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.
Exclusion Criteria:
* Patients who are pregnant or breastfeeding are not eligible.
* Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
* Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible. DRUG: Revumenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: intrathecal (IT) chemotherapy, DRUG: Cytarabine, DRUG: Methotrexate
Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Leukemia of Ambiguous Lineage, Myeloid and Monocytic Leukemia
Children’s Health
A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)
This pilot trial assesses the effect of the combination of blinatumomab with dasatinib or imatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (Ph+) or ABL-class Philadelphia chromosome-like (Ph-like) B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib and imatinib are in a class of medications called tyrosine kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib or imatinib in combination with standard chemotherapy may work better in treating patients with Ph+ or Ph-like ABL-class B-ALL than dasatinib or imatinib with chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
366 Days to 46 Years old
PHASE2
NCT06124157
STU20251198
Inclusion Criteria:
* Patients must be \> 365 days and \< 18 years (for AIEOP-BFM), \> 365 days and \< 22 years (for Children's Oncology Group \[COG\]) and \> 365 days and \< 46 years (for ALLTogether sites) at the time of enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):
* Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
* Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR
* Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
* Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])
* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment
Exclusion Criteria:
* Known history of chronic myeloid leukemia (CML)
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* ALL developing after a previous cancer treated with cytotoxic chemotherapy
* Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
* Down syndrome (trisomy 21)
* Pregnancy and breast feeding
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
* Lactating females who plan to breastfeed their infants
* Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol
* NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* 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 PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Biopsy, DRUG: Calaspargase Pegol, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Daunorubicin, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Imatinib, DRUG: Leucovorin, DRUG: Mercaptopurine, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Pegaspargase, DRUG: Prednisolone, DRUG: Prednisone, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine
B Acute Lymphoblastic Leukemia, Lymphoid Leukemia
Children’s Health
A Study Using Nivolumab, in Combination With Chemotherapy Drugs to Treat Nasopharyngeal Carcinoma (NPC)
This phase II trial tests effects of nivolumab in combination with chemotherapy drugs prior to radiation therapy patients with nasopharyngeal carcinoma (NPC). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Researchers want to find out what effects, good and/or bad, adding nivolumab to chemotherapy has on patients with newly diagnosed NPC. In addition, they want to find out if children with NPC may be treated with less radiation therapy and whether this decreases the side effects of therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
to 21 Years old
PHASE2
NCT06064097
STU-2024-0500
Inclusion Criteria:
* Patients must be ≤ 21 years of age at the time of study enrollment
* Newly diagnosed American Joint Committee on Cancer (AJCC) stage II-IV nasopharyngeal carcinoma (NPC)
* Patients must have had histologic verification of the malignancy at original diagnosis
* Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
* Patients must have had histologic verification of the malignancy at original diagnosis
* Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
* Patients must have a Lansky (for patients ≤ 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of ≥ 60%
* Peripheral absolute neutrophil count (ANC) ≥ 1000/uL (within 7 days prior to start of protocol therapy)
* Platelet count ≥ 100,000/uL (transfusion independent) (within 7 days prior to start of protocol therapy)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 or (within 7 days prior to start of protocol therapy)
* A serum creatinine based on age/sex (within 7 days prior to start of protocol therapy) Age: Maximum serum creatinine (mg/dL)
1 month to \< 6 months: 0.4 mg/dL (male); 0.4 mg/dL (female) 6 months to \< 1 year: 0.5 mg/dL (male); 0.5 mg/dL (female)
1 to \< 2 years: 0.6 mg/dL (male); 0.6 mg/dL (female) 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) 6 to \< 10 years 1 mg/dL (male); 1 mg/dL (female) 10 to \<13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
≥ 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and (within 7 days prior to start of protocol therapy)
* Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L\* (within 7 days prior to start of protocol therapy)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 50% by radionuclide angiogram
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and T-cell count above the lower limit of normal 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
Exclusion Criteria:
* Patients who received prior radiotherapy to the head or neck
* Patients who received prior chemotherapy or radiation for the treatment of any cancer in the last 3 years. These patients must also be in remission
* Patients with a diagnosis of immunodeficiency
* Patients with an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive agents). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Note: Patients with well-controlled asthma and no need for systemic steroids for the treatment of asthma in the last 12 months will not be excluded
* Patients with a condition requiring systemic treatment with either corticosteroids (\> 0.25 mg/kg (10 mg) daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 0.25 mg/kg (10 mg) daily prednisone equivalent, are permitted in the absence of active autoimmune disease
* Patients with a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Patients with detectable viral load of human immunodeficiency virus (HIV), hepatitis B or hepatitis C, or active tuberculosis
* Patients who have undergone solid organ or allogeneic hematopoietic transplant at any time
* Due to risks of fetal and teratogenic adverse events as seen in animal studies, a negative pregnancy test must be obtained in females of childbearing potential, defined as females who are post-menarchal. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 5 months after the last dose of nivolumab, 6 months after the last dose of gemcitabine, and 14 months after the last dose of cisplatin, whichever is longer
* Males of childbearing potential that are sexually active must agree to either practice a medically accepted highly-effective methods of contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 3 months after the last dose of gemcitabine, and 11 months after the last dose of cisplatin, whichever is longer
* Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy through 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 PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Chest Radiography, DRUG: Cisplatin, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, OTHER: Electronic Health Record Review, OTHER: Fluciclovine F18, DRUG: Gemcitabine, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, PROCEDURE: X-Ray Imaging
Stage II Nasopharyngeal Carcinoma AJCC v8, Stage III Nasopharyngeal Carcinoma AJCC v8, Stage IV Nasopharyngeal Carcinoma AJCC v8, Head and Neck
Children’s Health
Massive Transfusion in Children-2: A Trial Examining Life Threatening Hemorrhage in Children (MATIC-2)
The MATIC-2 is a multicenter clinical trial enrolling children who are less than 18 years of age with hemorrhagic shock potentially needing significant blood transfusion. The primary objective of the clinical trial is to determine the effectiveness of Low Titer Group O Whole Blood (LTOWB) compared to component therapy (CT), and Tranexamic Acid (TXA) compared to placebo in decreasing 24-hour all-cause mortality in children with traumatic life threatening hemorrhage.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Aguas@UTSouthwestern.edu
Barbara Gaines
ALL
to 17 Years old
PHASE3
NCT06070350
STU-2024-0064
General
• Children, defined as less than estimated18 years of age with traumatic injury
• MTP activation for confirmed or suspected active life-threatening traumatic bleeding AND Confirmed or suspected active life-threatening traumatic bleeding with at least 2 of 3 of the following criteria:
• Hypotension for age (\< 5% tile)
• Tachycardia for age (\>95th % tile)
• Traumatic injury with exam findings consistent with severe bleeding (e.g., penetrating injury, hemothorax, distended abdomen with bruising, amputation of limb). General
• Patient with devastating traumatic brain injury not expected to survive due to magnitude of injury (example: Transhemispheric gunshot wound with signs of herniation, GCS score of 3 with fixed and dilated pupils)
• MTP activated but no blood products given
• Patients who required an ED thoracotomy or received more than 5 consecutive minutes of cardiopulmonary resuscitation (prior to receiving randomized blood products)
• Patients who are known or suspected to be pregnant on clinical examination
• Known prisoners as defined in protocol
• Known ward of the state
• Isolated hanging, drowning or burns
• Previous enrollment in MATIC-2
• Prior study opt-out with bracelet Exclusion Criteria for the TXA/Placebo Domain
• Prehospital or pre-enrollment use of TXA
• Greater than 3 hours since time of injury
• History of seizure after the injury event
• Known allergy or hypersensitivity reaction to TXA
Inclusion Criteria:
• Children, defined as less than estimated18 years of age with traumatic injury
• MTP activation for confirmed or suspected active life-threatening traumatic bleeding AND Confirmed or suspected active life-threatening traumatic bleeding with at least 2 of 3 of the following criteria:
• Hypotension for age (\< 5% tile)
• Tachycardia for age (\>95th % tile)
• Traumatic injury with exam findings consistent with severe bleeding (e.g., penetrating injury, hemothorax, distended abdomen with bruising, amputation of limb). General
Exclusion Criteria:
• Patient with devastating traumatic brain injury not expected to survive due to magnitude of injury (example: Transhemispheric gunshot wound with signs of herniation, GCS score of 3 with fixed and dilated pupils)
• MTP activated but no blood products given
• Patients who required an ED thoracotomy or received more than 5 consecutive minutes of cardiopulmonary resuscitation (prior to receiving randomized blood products)
• Patients who are known or suspected to be pregnant on clinical examination
• Known prisoners as defined in protocol
• Known ward of the state
• Isolated hanging, drowning or burns
• Previous enrollment in MATIC-2
• Prior study opt-out with bracelet Exclusion Criteria for the TXA/Placebo Domain
• Prehospital or pre-enrollment use of TXA
• Greater than 3 hours since time of injury
• History of seizure after the injury event
• Known allergy or hypersensitivity reaction to TXA
BIOLOGICAL: Low Titer Group O Whole Blood (LTOWB), DRUG: Placebo, DRUG: Tranexamic Acid (TXA), BIOLOGICAL: Component Therapy (CT)
Hemorrhagic Shock, Trauma Injury
Children, Pediatrics, Transfusion
Children’s Health
A Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy (HINALEA 2)
This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered in pediatric participants with SMA and 2 SMN2 copies who previously received onasemnogene abeparvovec and experience a plateau or decline in function. Participants to be enrolled are children \<2 years of age genetically diagnosed with SMA.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Boudreau@UTSouthwestern.edu
Kaitlin Batley
ALL
3 Months to 24 Months old
PHASE4
NCT05861999
STU-2023-1071
Inclusion Criteria:
* \<2 years of age at the time of informed consent
* Confirmed diagnosis of 5q-autosomal recessive SMA, including genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the Survival of Motor Neuron 1 (SMN1) gene
* Confirmed presence of two SMN2 gene copies as documented through laboratory testing
* Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
* Has received onasemnogene abeparvovec for SMA no less than 13 weeks prior to enrollment
* If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration.
* In the opinion of the investigator, has demonstrated a plateau or decline in function post-gene therapy (with a duration of 26 weeks or less) documented by 2 individual time points in the functions as follows: swallowing AND one additional function/ability (respiratory, motor function, other) per appropriate expectation.
Exclusion Criteria:
* Previous or current enrolment in investigational study prior to initiation of study treatment
* Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
* Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide
* Concomitant or previous use of an anti-myostatin agent
* Participants requiring invasive ventilation or tracheostomy
* Presence of feeding tube and an OrSAT score of 0
* Hospitalization for pulmonary event within the last 2 months, or any planned hospitalization at the time of screening
* Any major illness requiring hospitalization within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to first dose administration. DRUG: Risdiplam
Muscular Atrophy, Spinal
Children’s Health
A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy (HINALEA 1)
This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered as an early intervention in pediatric participants with spinal muscular atrophy (SMA) and 2 SMN2 copies who have previously received onasemnogene abeparvovec. Participants are children \< 2 years of age genetically diagnosed with SMA.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Boudreau@UTSouthwestern.edu
Kaitlin Batley
ALL
3 Months to 24 Months old
PHASE4
NCT05861986
STU-2023-0862
Inclusion Criteria:
* \<2 years of age at the time of informed consent
* Confirmed diagnosis of 5q-autosomal recessive SMA, including genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the Survival of Motor Neuron 1 (SMN1) gene
* Confirmed presence of two SMN2 gene copies as documented through laboratory testing
* Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
* Has received onasemnogene abeparvovec for SMA no less than 13 weeks, but not more than months 30 weeks, prior to enrollment
* If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration
* Has, in the opinion of the investigator, not experienced clinically significant decline in function from the time of onasemnogene abeparvovec administration
Exclusion Criteria:
* Previous or current enrolment in investigational study prior to initiation of study treatment
* Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
* Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide
* Concomitant or previous use of an anti-myostatin agent
* Participants requiring invasive ventilation or tracheostomy
* Participants requiring awake non-invasive ventilation or with awake hypoxemia (Arterial Oxygen Saturation \[SaO2\] \<95%) with or without ventilator support
* Presence of feeding tube and an OrSAT score of 0
* Hospitalization for pulmonary event within the last 2 months, or any planned hospitalization at the time of screening
* Any major illness requiring hospitalization within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to first dose administration. DRUG: Risdiplam
Muscular Atrophy, Spinal, Other
Children’s Health
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART) (OptiSTART)
This study is designed to answer one of the fundamental gaps in knowledge in the resuscitation of preterm infants at birth: What is the optimal target oxygen saturation (SpO2) range that increases survival without long-term morbidities? Oxygen (O2) is routinely used for the stabilization of preterm infants in the delivery room (DR), but its use is linked with mortality and several morbidities including bronchopulmonary dysplasia (BPD). To balance the need to give sufficient O2 to correct hypoxia and avoid excess O2, the neonatal resuscitation program (NRP) recommends initiating preterm resuscitation with low (≤ 30%) inspired O2 concentration (FiO2) and subsequent titration to achieve a specified target SpO2 range. These SpO2 targets are based on approximated 50th percentile SpO2 (Sat50) observed in healthy term infants. However, the optimal SpO2 targets remain undefined in the preterm infants. Recent data suggest that the current SpO2 targets (Sat50) may be too low. The investigators plan to conduct a multicenter RCT of Sat75 versus Sat50 powered for survival without BPD. The investigators will randomize 700 infants, 23 0/7- 30 6/7 weeks' GA, to 75th percentile SpO2 goals (Sat75, Intervention) or 50th percentile SpO2 goals (Sat50, control). Except for the SpO2 targets, all resuscitations will follow NRP guidelines including an initial FiO2 of 0.3. In Aim 1, the investigators will determine whether targeting Sat75 compared to Sat50 increases survival without lung disease (BPD). In addition, the investigators will compare the rates of other major morbidities such as IVH. In Aim 2, the investigators will determine whether targeting Sat75 compared to Sat50 increases survival without neurodevelopmental impairment at 2 years of age. In Aim 3, the investigators will determine whether targeting Sat75 compared to Sat50 decreases oxidative stress.
Call 214-648-5005
studyfinder@utsouthwestern.edu, shelby.unger@UTSouthwestern.edu
Vishal Kapadia
ALL
0 Minutes to 10 Minutes old
NA
NCT05849077
STU-2022-0441
Inclusion Criteria:
-Neonates with OB gestational age 22-30 weeks
Exclusion Criteria:
* Prenatally diagnosed cyanotic congenital heart disease
* Prenatally diagnosed congenital diaphragmatic hernia
* Parents request no resuscitation
* If preductal saturations can not be measured by 3 minutes after pulse oximeter sensor is applied to the newborn OTHER: Sat75, OTHER: Sat50
Premature Infants, Bronchopulmonary Dysplasia, Intraventricular Hemorrhage, Neurodevelopmental Outcomes
neonatal resuscitation, oxygen
Children’s Health; Parkland Health & Hospital System
Safety and Efficacy Study of Viaskin Peanut in Peanut-allergic Children 4-7 Years of Age (VITESSE)
The primary purpose of this study is to assess the efficacy and safety of daily DBV712 250 micrograms (mcg) to induce desensitization to peanut in peanut-allergic children 4-7 years of age over a 12-month treatment period.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Priscilla.Arancivia@UTSouthwestern.edu
Malika Gupta
All
4 Years to 7 Years old
Phase 3
NCT05741476
STU-2023-0051
Key
• Aged 4 through 7 years at Visit 1 (screening).
• Physician-diagnosed peanut allergy or children with a well-documented medical history of IgE-mediated reactions after ingestion of peanut and currently following a strict peanut-free diet.
• Peanut-specific IgE of >0.7 kilo allergy unit per liter (kUA/L) and a positive peanut SPT with the largest wheal diameter of ≥6 millimeter (mm) at Visit 1.
• An ED of ≤100 mg peanut protein at screening DBPCFC. Key
• Severe generalized dermatologic disease involving the application area (interscapular region)
• Uncontrolled persistent asthma.
• Past or current immunotherapy for peanut allergy, including oral immunotherapy (OIT).
• Current immunotherapy for any allergen (including food allergy, allergic rhinitis and/or insect allergy), or treatment with any monoclonal antibody or biologic immunomodulatory therapy within 6 months prior to Visit 1.
Inclusion Criteria:
• Aged 4 through 7 years at Visit 1 (screening).
• Physician-diagnosed peanut allergy or children with a well-documented medical history of IgE-mediated reactions after ingestion of peanut and currently following a strict peanut-free diet.
• Peanut-specific IgE of >0.7 kilo allergy unit per liter (kUA/L) and a positive peanut SPT with the largest wheal diameter of ≥6 millimeter (mm) at Visit 1.
• An ED of ≤100 mg peanut protein at screening DBPCFC. Key
Exclusion Criteria:
• Severe generalized dermatologic disease involving the application area (interscapular region)
• Uncontrolled persistent asthma.
• Past or current immunotherapy for peanut allergy, including oral immunotherapy (OIT).
• Current immunotherapy for any allergen (including food allergy, allergic rhinitis and/or insect allergy), or treatment with any monoclonal antibody or biologic immunomodulatory therapy within 6 months prior to Visit 1.
Drug: DBV712, Other: Placebo
Allergy, Peanut, Other
Peanut Hypersensitivity, Epicutaneous Immunotherapy (EPIT), Epicutaneous, Immunotherapy, Viaskin, Nut and Peanut Hypersensitivity, Food Hypersensitivity, Peanut Allergy, Food Allergy, Nut and Peanut Allergy
Children’s Health
Comparison of Uncomplicated Candidemia Therapy Duration in Children (COUNT)
The goal of this clinical trial is to compare antifungal therapy duration in pediatric uncomplicated candidemia. The specific aims are: * Compare the desirability of outcome ranking in children with uncomplicated candidemia randomized to 7 additional days of antifungal therapy (standard-course) versus no additional antifungal therapy (short-course) after already receiving 7 days of echinocandin therapy. * Compare the 14-day desirability of outcome measure for subjects with a negative and those with a positive T2Candida® biomarker at day 7 of therapy within randomized groups. Participants meeting eligibility criteria will be approached and consented between day 5 and 7 of primary systemic antifungal therapy. On day 7 of primary systemic antifungal therapy, inclusion and exclusion criteria will again be reviewed for consented patients and those still eligible will be randomized 1:1 to the two study arms. Researchers will compare no additional antifungal therapy (short-course) versus 7 additional days of systemic antifungal therapy (standard-course) in pediatric patients with uncomplicated candidemia who have already received 7 days of primary systemic antifungal therapy to see if shorter durations are as effective as longer durations in treating uncomplicated candidemia.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aruna.Ayalasomayajula@UTSouthwestern.edu
Yeh-Chung Chang
ALL
120 Days to old
NA
NCT05763251
STU-2024-0378
Inclusion Criteria:
• Age \> 120 days at the time of the first negative blood culture at any participating site;
• Candidemia with at least one positive blood culture for any Candida spp;
• Receiving/received an echinocandin (caspofungin, micafungin, anidulafungin, or rezafungin) as primary antifungal therapy for candidemia for at least 2 days from day of first negative culture with continuation of uninterrupted systemic antifungal therapy at the time of enrollment);
• Sustained clearance of Candida spp. defined as negative blood culture(s) obtained after onset of candidemia and before day of randomization;
• Partial or complete clinical response, as defined by published guidelines (Table 5), on or before day of randomization;
• Between the onset of qualifying candidemia and randomization, no suspicion of disseminated candidiasis by patient's clinical team or, if deemed clinically necessary, documented negative radiological imaging such as an abdominal ultrasound or abdominal CT scan.
Exclusion Criteria:
• Already receiving antifungal therapy for a previously diagnosed systemic invasive fungal disease;
• Neutropenic (absolute neutrophil count \< 500 cells/µl) at the time of enrollment or anticipated to be neutropenic in the week following randomization;
• Have an underlying condition that requires them to be on antifungal prophylaxis when not receiving directed therapy for an invasive fungal disease;
• Previous enrollment in this trial;
• Females of childbearing age with a current pregnancy diagnosis or without a negative pregnancy test for their current admission;
• A documented DNR order;
• Have an implantable cardiac device (e.g., ventricular assist device, pacemaker)
OTHER: therapy duration
Invasive Candidiasis
Children’s Health
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma (EMERGE 101)
This study is conducted in two phases. The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin monotherapy in pediatric participants with previously treated solid tumors. This is followed by the phase 2 portion, to further assess the effectiveness and safety in pediatric and young adult participants with recurrent/refractory Ewing sarcoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
2 Years to 30 Years old
PHASE1
NCT05734066
STU-2023-0156
Key
Inclusion Criteria:
Age
* Participant must meet the following age requirements at the time the informed consent form (ICF) (and assent form, if applicable) is signed:
* Phase 1 Part 1: participants must be ≥ 2 to \< 18 years of age.
* Phase 1 Part 2: participants must be ≥ 2 to ≤ 30 years of age.
* Phase 2: participants must be ≥ 2 to ≤ 30 years of age.
Type of Participant and Disease Characteristics
* Participant has a confirmed solid tumor
* The participant has a Lansky/Karnofsky performance status score of ≥ 50%.
* The participant has adequate liver function, evidenced by the following laboratory values:
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN).
* Total bilirubin ≤ 1.5 × institutional ULN (with the exception of participants with Gilbert's syndrome who must have bilirubin \< 3 × institutional ULN).
* The participant has adequate bone marrow function, evidenced by the following:
* Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (independent of growth factor support within 1 week of screening laboratories).
* Platelets ≥ 100 × 109/L (without platelet transfusion within previous 7 days of screening laboratories).
* Hemoglobin ≥ 8 g/dL (note: may have been transfused).
* The participant has an adequate renal function:
* Calculated creatinine clearance (use Cockcroft-Gault formula for participants ≥ 18 years; Schwartz equation for participants \< 18 years) ≥ 60 mL/min.
* The participant has an adequate cardiac function:
* Left ventricular ejection fraction or shortening fraction per institutional norm ≥ institutional lower level of normal.
* The participant has creatine phosphokinase ≤ 2.5 × institutional ULN.
Weight
* The participant has body weight ≥ 15 kg.
Sex and Contraceptive/Barrier Requirements
Male participants:
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 4 months after the last dose of study intervention:
* Refrain from donating sperm.
PLUS, either:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
* Must agree to use contraception/barrier as detailed below:
* Agree to use a male condom with female partner and use of an additional highly effective contraceptive method with a failure rate of \< 1% per year when having sexual intercourse with a Woman of childbearing potential (WOCBP) who is not currently pregnant.
* Note: male participants who are azoospermic (vasectomized or due to a medical cause) are still required to follow the protocol-specified contraception/barrier criteria.
Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
* Is a Woman of nonchildbearing potential (WONCBP). OR
* Is a WOCBP and using an acceptable contraceptive method during the study intervention period (at least 7 months after the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 7 days before the first dose of study intervention.
* If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* Additional requirements for pregnancy testing during and after study intervention.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Informed Consent
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Key Exclusion Criteria:
Medical Conditions
* corrected QT interval (QTc) prolongation defined as a QTc ≥ 470 ms using the Bazett formula.
* Known symptomatic Central nervous system (CNS) metastases requiring steroids. Participants with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to enrollment, have discontinued high dose steroid treatment for these metastases for at least 2 weeks, and are neurologically stable (physiologic doses of steroids and short courses of steroids for other indications are acceptable).
* Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy, hypothyroidism, and rash Grade ≤ 2 are acceptable, and other Grade ≤ 2 adverse events (AEs) not constituting a safety risk based on the investigator's judgement are acceptable.
* An uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with participation in this study.
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high-risk for treatment complications.
Prior/Concomitant Therapy
* Received prior treatment with lurbinectedin or trabectedin.
* Received prior treatment with any investigational product within 4 weeks of first infusion of study intervention. Observational studies are permitted.
* Received live or live attenuated vaccines within 4 weeks of the first dose of study treatment or plans to receive live vaccines during study participation. Administration of inactive vaccines or messenger ribonucleic acid (mRNA) vaccines (for example, inactivated influenza vaccines or COVID-19 vaccines) are allowed.
* Had major surgery ≤ 4 weeks or radiation therapy ≤ 2 weeks prior to enrollment unless fully recovered. Prior palliative radiotherapy is permitted, provided it was completed at least 2 weeks prior to participant enrollment.
* Received prior allogeneic bone marrow transplantation or solid organ transplant.
* Received chemotherapy ≤ 3 weeks prior to start of study intervention.
Diagnostic Assessments
* Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or Polymerase chain reaction (PCR) test for HCV RNA if HCV antibody test is positive).
* Human immunodeficiency infection at screening (positive anti-HIV antibody).
Other Exclusions
* Has a known or suspected hypersensitivity to any of the components of the study intervention.
* The participant or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator DRUG: Lurbinectedin
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma, Ewing Sarcoma, Sarcoma
Solid Tumors, lurbinectedin, ewing's sarcoma, soft tissue sarcoma, sarcomas
Children’s Health
A Study of the Drug Letermovir as Prevention of Cytomegalovirus Infection After Stem Cell Transplant in Pediatric Patients
This phase III single arm trial determines whether taking prophylactic letermovir will reduce the likelihood of infection with cytomegalovirus (CMV) in children and adolescents after stem cell transplant compared to estimated rate of infection without prophylaxis. The treatments used to prepare for hematopoietic cell transplant (HCT) reduce the body's natural infection-fighting ability and increase the likelihood of an infection with a virus called cytomegalovirus. "Prophylaxis" means to take a drug to prevent a disease or side effect. Letermovir is an antiviral drug that stops cytomegalovirus from multiplying and may prevent cytomegalovirus infection and make the disease less severe.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Victor Aquino
ALL
2 Years to 18 Years old
PHASE3
NCT05711667
STU-2024-0632
Inclusion Criteria:
* \>= 2 years and \< 18 years at the time of enrollment
* Weight must be \>= 6 kg at the time of enrollment
* Planned allogeneic HCT (bone marrow, peripheral blood stem cell, or cord blood transplant)
* Patient must be CMV sero-positive (i.e., recipient CMV immunoglobulin G positive)
* Note: If a patient has hypogammaglobulinemia but has previously been documented as CMV sero-positive, that is acceptable for study inclusion. For all patients already confirmed to be CMV IgG seropositive, repeat testing is not required within 7 days prior to enrollment. However, the laboratory data determining eligibility must be available in the patient's medical/research record for verification
* Patient is eligible for entry only if it is feasible for plasma CMV PCR testing to be sent and resulted within the protocol mandated time period
* Reminder: To limit the likelihood of positive plasma CMV PCR post-enrollment and prior to start of study treatment period, it is recommended that patient enrollment proceed after patients start their transplant preparative regimen
* Patient must have a performance status corresponding to Lansky/Karnofsky scores \> 50
* Note: Use Lansky for patients =\< 16 years of age and Karnofsky for patients \> 16 years of age. For further reference, see performance status scales scoring under the standard sections for protocols among protocol reference materials provided on the Children's Oncology Group (COG) member website: https://members.childrensoncologygroup.org/prot/reference\_materials.asp
* Estimated glomerular filtration rate \> 10 mL/min/1.73 m\^2 and not receiving dialysis
* Direct bilirubin =\< 2 mg/dL and serum glutamate-pyruvate transaminase (SPGT) (alanine transaminase \[ALT\]) =\<10 x upper limit of normal (ULN) for age
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
Exclusion Criteria:
* Expected inability to tolerate oral formulation of letermovir
* Hypersensitivity to letermovir or any component of the formulation
* History of CMV end organ disease within 6 months (180 days) prior to enrollment
* Note: CMV end organ disease based on proposed definitions by Ljungman et al. and inclusive of proven, probable or possible disease
* Receipt of prior allogeneic HCT within one year of study enrollment
* Planned prophylactic administration of other anti-CMV medications or cellular products during the study, including:
* High dose acyclovir (defined as doses \>= 1500 mg/m\^2 IV or \>= 3200 mg oral (patients \>= 40 kg) or \>= 2400 mg/m\^2 (patients \< 40 kg) per day)
* High dose valacyclovir (defined as doses \>= 3000 mg/day in patients \> 20 kg)
* Foscarnet
* Ganciclovir
* Valganciclovir
* CMV-directed cytotoxic T lymphocytes
* Planned receipt of the following contraindicated medications during the study treatment period; contraindicated medications must be discontinued at least 14 days prior to Day +1
* Contraindicated medications for all patients:
* Pimozide
* Ergot alkaloids
* Contraindicated medications for patients planned to receive cyclosporine:
* Bosentan
* Pitavastatin
* Simvastatin
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted in certain animal reproduction studies with letermovir. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active female patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their letermovir treatment and through at least 4 weeks after the last dose of letermovir.
* Note: No contraception measures are needed specifically during letermovir treatment for male trial participants who have pregnant or non-pregnant female partner(s) of reproductive potential. Contraception measures may be required for other aspects of the HCT procedure.
* 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 PROCEDURE: Biospecimen Collection, DRUG: Letermovir
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Other
Children’s Health
A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions as Adoptive Immunotherapy in Combination With Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Pediatric Bone and Soft Tissue (TINKS)
The purpose of this study is to determine if the addition of infusions of a type of immune cell called a "natural killer", or NK cell to the sarcoma chemotherapy regimen GEM/DOX (gemcitabine and docetaxel) can improve outcomes in people with childhood sarcomas that have relapsed or not responded to prior therapies. The goals of this study are: * To determine the safety and efficacy of the addition of adoptive transfer of universal donor, TGFβ imprinted (TGFβi), expanded NK cells to the pediatric sarcoma salvage chemotherapeutic regimen gemcitabine/docetaxel (GEM/DOX) for treatment of relapsed and refractory pediatric sarcomas To determine the 6-month progression free survival achieved with this treatment in patients within cohorts of relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma. * To identify toxicities related to treatment with GEM/DOX + TGFβi expanded NK cells Participants will receive study drugs that include chemotherapy and NK cells in cycles; each cycle is 21 days long and you can receive up to 8 cycles. * Gemcitabine (GEM): via IV on Days 1 and 8 * Docetaxel (DOX): via IV on Day 8 * Prophylactic dexamethasone: Day 7-9 to prevent fluid retention and hypersensitivity reaction * Peg-filgrastim (PEG-GCSF) or biosimilar: Day 9 to help your white blood cell recover and allow more chemotherapy to be given * TGFβi NK cells: via IV on Day 12
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
2 Years to 40 Years old
PHASE1
NCT05634369
STU-2023-0706
Inclusion Criteria:
• Patients must be between the ages ≥ 2 years and ≤ 40 years of age and have had a relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma.
• Patients must have measurable disease using RECIST 1.1 criteria
• Patients must have had at least one and no more than four total lines of cytotoxic systemic treatment for relapse sarcoma. Local control with surgical resection or radiation therapy of the primary tumor and any metastatic sites as clinically indicated as standard of care per the treating physician must be considered prior to enrollment.
• Prior Therapy: Therapy may not have been received more recently than the timeframes defined below: * Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 14 days of protocol therapy * Radiation: At least 2 weeks must have elapsed from the start of protocol therapy since local palliative XRT (small port); 4 weeks must have elapsed for all other radiation therapy * Hematopoietic Cell Transplant (HCT): Patients must have at least 6 weeks elapsed after autologous and allogeneic hematopoietic cell transplant * Biologic (anti-neoplastic agent): At least 7 days or 5 half-lives of the drug, whichever is longer, must have elapsed from the start of protocol therapy since the completion of therapy with a biologic agent. * Monoclonal antibodies: At least 3 weeks must have elapsed from the start of protocol therapy since prior therapy that included a monoclonal antibody. * Prior use of Gemcitabine and/or Docetaxel: Patients who have received these agents for prior treatment may be included if previous treatments were given ≥ 6 months prior to enrollment on this study, and there were no allergic reactions, pulmonary edema or fibrosis, Grade 3 or higher neuropathy or other non-hematologic Grade 4 adverse events related to gemcitabine and/or docetaxel therapies. 4\) Performance status: Karnofsky ≥ 60 for patients ≥16 years of age. Lansky score of ≥ 60 for patients \< 16 years of age (see Appendix A) 5) Organ Function Requirements: Patients must have normal organ and marrow function within 7 days of starting protocol therapy as defined below: * Absolute Neutrophil Count ≥1000/mcL * Platelet count ≥100,000/mcL transfusion independent defined as no platelet transfusions within the last 72 hours * Total bilirubin \< 1.5x upper limit of normal for age * AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal * Serum creatinine \< 1.5 x upper limit of normal based on age/gender (Table 3) OR creatinine clearance ≥70 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Shortening fraction ≥ 27% by ECHO OR ejection fraction of ≥ 50% by ECHO or gated radionuclide study * Echocardiogram done within 12 months of study entry will be acceptable. If patient has required anthracycline chemotherapy since last ECHO and enrollment on this study, echocardiogram should be repeated. * No evidence for dyspnea at rest, no chronic oxygen requirement, and room air pulse oximetry \>94% if there is a clinical indication for pulse oximetry 6) Neuropathy: Patients must have ≤ Grade 2 neuropathy at enrollment 7) Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsant, with the exception of diazepam given its potential deleterious effects on NK cell activity. 8\) Contraception: The effects of expanded NK cells on the developing human fetus are unknown. For this reason and because the chemotherapeutic preparative agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of preparatory regimen administration. 9\) All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document.
Exclusion Criteria:
• Patients who are receiving any other investigational agents.
• Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer
• Patients with a history of allergic reactions attributed to docetaxel, gemcitabine, or peg-filgrastim or biosimilar
• Patients who have received any prior cellular therapies, such as CAR-T cells or other expanded or manufactured cellular products.
• Patients with bone marrow only disease are not eligible for this study.
• Patients with any of the following "Intermediate" (rarely metastasizing) or "malignant" Grade 2 or Grade 3 tumors of any size, as defined in the WHO Classification of Soft Tissue Tumors are not eligible for this study: * So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues * Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma * Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumour, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), initial sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor * Chondro-osseous tumors - extraskeletal osteosarcoma * Pericytic (perivascular) tumors - malignant glomus tumor * Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor * Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
• Patients who, in the judgment of the treating physician, has tumors near critical structures for which transient swelling would cause substantial symptoms, such as tumor within the bowel mucosa
• Patients with CNS metastatic disease will not be eligible for this study.
• Concomitant Medications: * Due to their effect on NK cell function, systemic corticosteroids outside of the supportive dexamethasone given from day 7 through 9 should be used ONLY for life-threatening conditions (i.e., life-threatening allergic reactions and anaphylaxis such as bronchospasm, stridor) unresponsive to other measures. The use of dexamethasone as an anti-emetic is not permitted. Corticosteroid therapy can be used as a premedication for transfusion in patients known to have a history of transfusion reactions or for treatment of an unexpected transfusion reaction (hydrocortisone 2 mg/kg or less or an equivalent dose of an alternative corticosteroids). The use of steroids during protocol therapy other than the study- required prophylactic dexamethasone doses requires clear justification and documentation of use for a life-threatening condition. * The following are also prohibited while on study treatment * Strong CYP3A4 inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians' Desk Reference may also provide this information. * Diazepam * Chemotherapeutic agents other than the study drugs
• Uncontrolled intercurrent illness including, but not limited to: * ongoing or active infection * psychiatric illness/social situations that would limit compliance with study requirements
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies with Gemcitabine and Docetaxel
• HIV Infection: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study medications. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
BIOLOGICAL: GEM/DOX + TGFBi expanded NK cells
Pediatric Sarcoma, Refractory, Pediatric Sarcoma, Relapsed, Bones and Joints, Sarcoma, Soft Tissue
Children’s Health
Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants (PIVOTAL)
Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment. There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Emilie.Vannguyen@UTSouthwestern.edu
Sushmita Yallapragada
ALL
7 Days to 32 Days old
NA
NCT05547165
STU-2022-1102
Inclusion Criteria:
• EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive
• Admitted to a study NICU
• Birth weight ≥700-grams
• Mechanically ventilated at time of consent and randomization
• HSPDA ("PDA Score" ≥6) noted on echocardiogram (ECHO)
• Randomization is able to be performed within 5 days of the qualifying ECHO and when infant is 7-32 days postnatal
Exclusion Criteria:
Clinical Exclusion Criteria
• Life-threatening congenital defects (including congenital heart disease such as aortic coarctation or pulmonary artery stenosis). PDA and small atrial/ventricular septal defects are permitted;
• Congenital lung abnormalities, (e.g. restrictive lung disease);
• Pharyngeal or airway anomalies (tracheal stenosis, choanal atresia);
• Treatment for acute abdominal process (e.g., necrotizing enterocolitis);
• Infants with planned surgery;
• Active infection requiring treatment;
• Chromosomal defects (e.g., Trisomy 18);
• Neuromuscular disorders;
• Infants whose parents have chosen to allow natural death (do not resuscitate order) or for whom limitation of intensive care treatment is being considered (e.g. severe intraventricular hemorrhage)
• Physician deems that the infant would not be a Percutaneous PDA Closure candidate due to clinical instability; however, if the infant's clinical status improves before 30-days postnatal and all inclusion criteria are still met, then the infant may be enrolled. ECHO-based Exclusion Criteria
• Pulmonary hypertension (defined by ductal right to left shunting for \>33% of the cardiac cycle) in which early PDA closure may increase right ventricular afterload and compromise pulmonary and systemic blood flow;
• Evidence of cardiac thrombus that might interfere with device placement;
• PDA diameter larger than 4 mm at the narrowest portion (consistent with FDA-approved instructions for Piccolo™ device use).
• PDA length smaller than 3 mm (consistent with FDA-approved instructions for Piccolo™ device use).
• PDA that does not meet inclusion requirements ("PDA Score" \<6).\* \* If a potential participant is found to have a PDA meeting eligibility requirements on a subsequent ECHO during the required period of 7 - 30 postnatal days of age, they may then be declared eligible to participate and enrolled, provided all other inclusion criteria are met and exclusion criteria are not met. Other Exclusion Criteria
• Parents or legal guardian do not speak English or Spanish
DEVICE: Percutaneous Patent Ductus Arteriosus Closure (PPC), COMBINATION_PRODUCT: Responsive Management Intervention, DIAGNOSTIC_TEST: Echocardiogram, cardiac
Ductus Arteriosus, Patent
PDA
Children’s Health
Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma
This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
to 59 Months old
PHASE2
NCT05535166
STU-2023-0119
Inclusion Criteria - Screening Phase (All Patients)
* Participants with presumptive/suspected newly diagnosed medulloblastoma.
* Participant meets one of the following criteria at the time of screening:
* Age \< 36 months OR Age ≥ 36 months and \< 60 months with presumptive/suspected non-metastatic disease
* Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC
* Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).
* Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.
Exclusion Criteria - Screening Phase
* Participants with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedure.
Inclusion Criteria - Study Enrollment (All Patients)
* Participant must be \< 60 months of age at time of enrollment.
* Note: Each treatment stratum has additional specific age requirements
* Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
* Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group/subgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under "SHH-NOS", and all NWNS and indeterminate molecular group will be enrolled on stratum N.
* Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.
* Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF\* and be placed into the following categories:
* M0: no evidence of metastatic disease.
* must include a negative CSF cytology result
* M1: Tumor cells found in the CSF but no other evidence of metastasis
* M2: Intracranial tumor beyond the primary tumor site
* M3: Metastatic disease in the spine
* M4: Extraneural metastatic disease
* \*All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB21. The decision to enroll without CSF cytology will be made on case-by-case basis.
* Note: Participants who have M2 disease and positive CSF will be assigned to M3.
* Note: Participants will be assigned to the highest stage number for which they meet eligibility.
* Note: Treatment stratums may have additional stage requirements.
* Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.
* Participant must have a Lansky performance score of \> 30 (except for patients with posterior fossa syndrome.
* Participant must have adequate organ function prior to study entry, as defined by:
* Absolute neutrophil counts (ANC) \>750/mm\^3
* Platelet count ≥ 50,000/mm\^3 without support of a platelet transfusion within 7 days
* Hemoglobin ≥8.0 g/dL (with or without support of a blood transfusion).
* Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U/L and total bilirubin ≤ 3 x 1.0.
* Adequate renal function as defined by a serum creatinine concentration:
* Age - 0 to \<1year; Maximum Serum Creatinine (mg/dl) - Male 0.5; Female 0.5
* Age - 1 to \< 2years; Maximum Serum Creatinine (mg/dl) - Male 0.6; Female 0.6
* Age - 1 to \< 2yearsr; Maximum Serum Creatinine (mg/dl) - Male 0.8; Female 0.8
* Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Inclusion Criteria - Stratum S-2
* Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
* Medulloblastoma SHH-2
* Participant must meet one of the following criteria at time of enrollment:
* Age \<36 months OR Age ≥ 36 months and \< 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma SHH-1
* Medulloblastoma SHH-3
* Medulloblastoma SHH-4
* Medulloblastoma SHH-NOS
* Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and/or cases defined as SHH by IHC.
* Participant must be \< 36 months of age at time of enrollment
* Note: Patients who are \< 36 months of age, regardless of metastatic status (M0/M+), are eligible for enrollment on stratum S-1.
Inclusion Criteria - Stratum N
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma G3
* Medulloblastoma G4
* Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
* Includes medulloblastoma cases that could not be assigned to a molecular group using the DNA methylation classifier but which are in the NWNS class and/or defined as NWNS by IHC.
* Participant must be \<36 months of age at time of enrollment
* All NWNS patients (M+ and M0) are eligible for enrollment in stratum N
Exclusion Criteria - All Patients
* CNS embryonal tumor other than medulloblastoma, for example, patients with diagnosis of Atypical Teratoid/Rhabdoid Tumor (ATRT), PNET, Pineoblastoma, Ependymoma, and ETMR are excluded.
* Participant with prior treatment for medulloblastoma, including:
* Radiotherapy
* Chemotherapy
* Cancer directed immunotherapy
* Targeted agents
* NOTE: Corticosteroid therapy is acceptable; prior treatment with chemotherapy, immunotherapy or targeted agents for non-cancer directed indications are acceptable as long as these have been stopped at least 14 days prior to start of therapy or 2 half-lives from last dose. (i.e., methotrexate for juvenile rheumatoid arthritis, JAK inhibitor therapy for eczema, etc.)
* Participant who is actively receiving any other investigational agents.
* Participant with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results.
PROCEDURE: Surgical resection, PROCEDURE: Ommaya/VPS, DRUG: Methotrexate, DRUG: Cisplatin, DRUG: Vincristine, DRUG: Cyclophosphamide, DRUG: Carboplatin, DRUG: Topotecan, DRUG: Etoposide, DRUG: Pegfilgrastim, DRUG: Filgrastim, RADIATION: Irradiation, OTHER: Educational and Media Intervention, OTHER: SOC, Educational and Media Intervention, DRUG: Methotrexate
Medulloblastoma, Brain and Nervous System
SJiMB21, Brain Cancer, Brain Tumors in Children, Medulloblastoma Sonic Hedgehog subgroup 1, Medulloblastoma Sonic Hedgehog subgroup 2, Medulloblastoma Sonic Hedgehog subgroup 3, Medulloblastoma Sonic Hedgehog subgroup 4, Medulloblastoma Sonic Hedgehog-not otherwise specified, Medulloblastoma G3, Medulloblastoma G4, Medulloblastoma indeterminate, MLPNet, Neural Net Classification Pipeline, Non-WNT non-SHH medulloblastoma, Posterior fossa syndrome, St. Jude Brain Tumor Studies, Treatment for Brain Tumors in Infants and Young Children, Untreated Childhood Medulloblastoma
Children’s Health