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Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
MELPIDA is proposed for the treatment of subjects with SPG50 and targets neuronal cells to deliver a fully functional human AP4M1 cDNA copy via intrathecal injection to counter the associated neuronal loss. Outcomes will evaluate the safety and tolerability of a single dose of MELPIDA, which will be measured by the treatment-associated adverse events (AEs) and serious adverse events (SAEs). Secondarily, the trial will explore efficacy in terms of disease burden assessments.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sydney.Cooper@UTSouthwestern.edu
Susan Iannaccone
ALL
4 Months to 10 Years old
PHASE1
NCT05518188
STU-2022-0886
Inclusion Criteria:
• Age 4 months-10 years old
• Confirmed diagnosis of SPG50 disease by:
• Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the AP4M1 gene
• Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction
• Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study
• Subject able to comply with all protocol requirements and procedures
• Ability to stand for more than 5 seconds OR
• Ability to take 5 steps independently or with a walker OR
• Modified Ashworth Scale score 2 or below (Ankles).
Exclusion Criteria:
• Inability to participate in study procedures (as determined by the site investigator)
• Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics
• History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy
• Inability to be safely sedated in the opinion of the clinical anesthesiologist
• Active infection, at the time of dosing, based on clinical observations
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
• Inability of the patient to undergo MRI according to local institutional policy
• Inability of the patient to undergo any other procedure required in this study
• The presence of significant non-SPG50 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
• Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
• Enrollment and participation in another interventional clinical trial
• Contraindication to MELPIDA or any of its ingredients
• Contraindication to any of the immune suppression medications used in this study
• Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin \> 3 × ULN, creatinine ≥ 1.5 mg/dL, hemoglobin \[Hgb\] \< 6 or \> 20 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy.
BIOLOGICAL: MELPIDA
Spasticity, Muscle, Microcephaly, Intellectual Deficiency, Growth Retardation, SPG50, Spastic Paraplegia
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 214-648-5005
studyfinder@utsouthwestern.edu, tawny.hank@childrens.com
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
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
Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Down Syndrome (TOPS-DS) (TOPS-DS)
The overall objective of this randomized clinical trial is to test the effectiveness of a personalized approach to the surgical treatment of OSA in children with Down syndrome (DS).The estimated prevalence of obstructive sleep apnea (OSA) in children with DS ranges from 45-83%, compared to 1-6% in the general pediatric population. Untreated OSA in children has been associated with daytime sleepiness, cognitive or behavioral problems, and cardiovascular complications, all which are common in children with DS. Adenotonsillectomy (AT) is the first line treatment for OSA in children, however, most large studies of AT outcomes have excluded children with DS. Available evidence demonstrates that AT is far less effective in children with DS than in the general pediatric population, with 48 to 95% of children with DS having persistent OSA after AT. Medical treatments such as positive airway pressure (PAP) therapy are frequently inadequate or poorly tolerated in this population, so many children with DS and OSA remain untreated. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites and patterns of obstruction during sedated sleep using a flexible endoscope passed through the nose into the pharynx. DISE was developed to guide surgical decisions in adult OSA, and in recent years has also been used to design personalized surgical interventions in children. Using this DISE Rating Scale, the investigators have demonstrated that children with DS are more prone to tongue base and supraglottic obstruction than non-DS children, suggesting the need for more personalized surgical treatments that are tailored to the common sources of obstruction in this population. Several small case series demonstrate that DISE-directed surgery can be effective in treating OSA in children with DS. However, because there have been few prospective studies and no randomized trials comparing different treatment options in this population, there remains uncertainty about whether such a personalized approach leads to superior outcomes compared to the first line AT. It is the investigators' hypothesis that personalized DISE-directed surgery that uses existing procedures to address specific fixed and dynamic anatomic features causing obstruction in each child with DS will be superior to the current first line approach of AT. This novel approach may improve OSA outcomes and reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an ineffective AT.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Francesca.Chambers@UTSouthwestern.edu
Ron Mitchell
ALL
2 Years to 17 Years old
NA
NCT05508971
STU-2022-0838
Inclusion Criteria:
Child has a diagnosis of Down syndrome (Trisomy 21). Child has a diagnosis of moderate to severe OSA diagnosed by PSG (oAHI ≥ 5). Child age is 2.00 to 17.99 years of age. Caregiver can provide signed and dated consent and is 18 years of age or older at the time of consent.
Caregiver can speak, read, and write in English or Spanish. Caregiver is primary caretaker of the child. Child is not pregnant. Child is eligible for surgical treatment
Exclusion Criteria:
Child has history of previous tonsillectomy, tonsillotomy, or partial tonsillectomy.
Child has any contraindication to surgery (e.g. bleeding disorders). Child has significant cardiopulmonary comorbidity besides OSA requiring supplemental oxygen, subglottic or tracheal stenosis, tracheostomy dependence.
Caregiver is unwilling or unable to comply with study procedures. Child is or plans to become pregnant. PROCEDURE: DISE-Directed Surgery, PROCEDURE: Adenotonsillectomy
Obstructive Sleep Apnea, Down Syndrome
Children’s Health
Efficacy, Safety, and Pharmacokinetics of Leuprolide Mesylate in Subjects with Central Precocious Puberty
The study will evaluate if Leuprolide Mesylate is safe and effective in the treatment of subjects with central (gonadotropin-dependent) precocious puberty, when administered as two injections six months apart.
Call 214-648-5005
studyfinder@utsouthwestern.edu, colten.youngblood@childrens.com
Perrin White
ALL
2 Years to 9 Years old
PHASE3
NCT05493709
STU-2023-0726
Inclusion Criteria:
• Females aged 2 to 8 years (inclusive) or males aged 2 to 9 years (inclusive).
• Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRHa treatment for CPP.
• Pubertal-type LH response at 60 minutes post GnRHa stimulation test before treatment initiation \> 5 mIU/mL.
• Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males.
• Willing and able to participate in the study.
• Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year.
• Bone age \< 13 years for girls and \< 14 years for boys.
• Signed Institutional Review Board/Independent Ethics Committee (IRB/IEC)-approved informed consent form (ICF) by one or both parents (per IRB/IEC requirements), by the custodial parent(s) or by the legal guardian(s) (if required).
• Signed Assent by patients as per IRB/IEC requirements.
Exclusion Criteria:
• Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion. This includes true CPP triggered by other conditions, such as congenital adrenal hyperplasia.
• Prior or current GnRH treatment for CPP.
• Non-progressing isolated premature thelarche.
• Presence of an unstable intracranial tumor or an intracranial tumor requiring neurosurgery or cerebral irradiation. Patients with hamartomas or adenomas not requiring surgery are eligible.
• Any other condition, chronic illness or treatment that, in the opinion of the Investigator, may interfere with growth or other study endpoints (e.g., chronic steroid use \[except mild topical steroids\], renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor).
• Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1).
• Major medical or psychiatric illness that could interfere with study visits.
• Diagnosis of short stature (i.e., 2.25 standard deviations (SD) below the mean height for age).
• Positive urine pregnancy test.
• Known hypersensitivity to GnRH or related compounds.
• Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patients to participate in the study.
• Any other condition(s) which could significantly interfere with Protocol compliance.
• Treatment with an investigational product within 5 half-lives of that product in prior clinical studies before the baseline visit (Day 0).
• Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions.
• Prior (within 6 months of Baseline (Day 0)) or current use of medications that, per Investigator opinion, have been associated with seizures or convulsions.
DRUG: Leuprolide Mesylate, Subcutaneous injection of 42 mg Leuprolide
Puberty, Precocious, Central
Children’s Health
A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic). RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide. 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 cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. 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. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
up to 18 Years old
PHASE2
NCT05504291
STU-2023-0581
Inclusion Criteria:
* Patient must be \< 18 years of age at enrollment
* Patient must have newly diagnosed intraocular (localized) retinoblastoma and meet one of the following criteria:
* Unilateral Group D retinoblastoma with vitreous seeding; OR
* Bilateral retinoblastoma with worst eye Group D, with vitreous seeding present and the contralateral eye is Group A-C; OR
* Bilateral Group D retinoblastoma with at least one eye with vitreous seeding; OR
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has been enucleated prior to any therapy. Note exclusion for high-risk features
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has not been enucleated prior to any therapy at the discretion of the treating physician. Note exclusion for patients with evidence of metastatic or extra orbital spread
* 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
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Platelet count \>= 75,000/uL (transfusion independent) (must be performed within 7 days prior to enrollment)
* A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment):
* 1 month to \< 6 months = 0.4 (male and female)
* 6 months to \< 1 year = 0.5 (male and female)
* 1 to \< 2 years = 0.6 (male and female)
* 2 to \< 6 years = 0.8 (male and female)
* 6 to \< 10 years = 1.0 (male and female)
* 10 to \< 13 years = 1.2 (male and female)
* 13 to \< 16 years = 1.5 (male) and 1.4 (female)
* \>= 16 years = 1.7 (male) and 1.4 (female) OR - a 24-hour urine Creatinine clearance \>= 70 mL/min/1.73 m\^2 OR - a glomerular filtration rate (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
* For patients \< 1 month of age, serum creatinine levels must be \< 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients \< 1 month of age or the creatinine clearance or radioisotope GFR must be \>= 70 mL/min/1.73 m\^2
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
Exclusion Criteria:
* Patients with evidence of metastatic or extra-orbital spread
* Patients must not have an invasive infection at time of protocol entry
* Patients must not have had any prior anti-cancer therapy other than cryotherapy and/or laser therapy (green or infrared) to the study eye(s) and non-study eye, including systemic chemotherapy, intra-arterial chemotherapy, radioactive plaque, brachytherapy, or radiation therapy.
* Note: A study eye is defined as being Group D with vitreous seeding. Patients may have had enucleation of one eye as long as the remaining eye is Group D with vitreous seeds
* Patients with bilateral disease who undergo enucleation of a Group E eye prior to initiation of therapy and show evidence of high-risk histopathology features in the enucleated eye. High-risk histopathology includes choroid involvement \>= 3 mm, post lamina optic nerve involvement, full thickness scleral invasion or optic nerve invasion to the cut end
* 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, DRUG: Carboplatin, DRUG: Etoposide, PROCEDURE: Examination Under Anesthesia, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan, PROCEDURE: Ultrasound Biomicroscopy, DRUG: Vincristine
Bilateral Retinoblastoma, Childhood Intraocular Retinoblastoma, Group D Retinoblastoma, Stage I Retinoblastoma, Unilateral Retinoblastoma, Eye and Orbit
Children’s Health
MASA Valve Early Feasibility Study (MVEFS)
The MASA Valve Early Feasibility Study (MVEFS) multi-site interventional clinical trial within the United States of America with each center following a common protocol.The objective of the trial is to evaluate the safety and probable benefit of MASA Valve in the indicated subset of patients requiring Right Ventricular Outflow Tract Reconstruction (RVOTR). As an early feasibility study, the purpose is determine the feasibility of success of the device in order to gather early data towards a future pivotal study and/or regulatory clearance submission.
Call 214-648-5005
studyfinder@utsouthwestern.edu, madison.munson@childrens.com
Karl Reyes
All
0 Years to 22 Years old
N/A
NCT05452720
STU-2023-0657
Inclusion Criteria:
• At least one of the following: Right Ventricular to Pulmonary Artery mean gradient > 35mm Hg, moderate or severe Pulmonary regurgitation (≥3+), or clinical indication for replacement of their native or prosthetic pulmonary valve with a prosthesis.
• Age < 22 years
• Patient is geographically stable and willing to return for 1 year follow-up for the trial.
• Patient's legal guardian should be willing to provide informed consent (IC) at the hospital location where they are being enrolled.
• The patient, and the patient's parent / legal representative where appropriate, and the treating physician agree that the subject will return for all required post-procedure follow up visits and the subject will comply with clinical investigation plan required follow-up visits.
Exclusion Criteria:
• Patient is in need of or has presence of a prosthetic heart valve at any other position
• Patient has a need for concomitant surgical procedures (non-cardiac)
• Patients with previously implanted pacemaker (including defibrillators) or mechanical valves
• Patient has an active bacterial or viral infection or requiring current antibiotic therapy (if temporary illness, patient may be a candidate 4 weeks after discontinuation of antibiotics)
• Patient has an active endocarditis
• Leukopenia, according to local laboratory evaluation of white blood cell count
• Acute or chronic anemia, according to local laboratory evaluation of hemoglobin Patients can be transfused to meet eligibility criteria
• Thrombocytopenia, defined as Platelet count < 150,000/mm3 Patients can be transfused to meet eligibility criteria
• Severe chest wall deformity, which would preclude placement of the PV conduit
• Known hypersensitivity to anticoagulants and antiplatelet drugs and to the device materials
• Immunocompromised patient defined as: autoimmune disease, patients receiving immunosuppressant drugs or immune stimulant drugs
• Patient has chronic inflammatory / autoimmune disease
• Need for emergency cardiac or vascular surgery or intervention
• Major or progressive non-cardiac disease (liver failure, renal failure, cancer) that has a life expectancy of less than one year
• Currently participating, or participated within the last 30 days, in an investigational drug or device study
• Alcohol or drug abuse as defined by DSM IV-TR criteria for substance abuse - this includes the illicit use of cannabis within the last 12 months
• Patient has medical, social or psychosocial factors that, in the opinion of the Investigator, could have impact on safety or compliance
Device: Surgical Right Ventricular Outflow Tract Reconstruction
Tetrology of Fallot, Pulmonary Stenosis, Truncus Arteriosus, Transposition of Great Vessels, Pulmonary Atresia, Ross Procedure
Right Ventricular Outflow Tract Reconstruction, Pulmonary Valve, MASA Valve, Pulmonary Valve Replacement
Children’s Health
Mismatched Related Donor Versus Matched Unrelated Donor Stem Cell Transplantation for Children, Adolescents, and Young Adults With Acute Leukemia or Myelodysplastic Syndrome
This phase III trial compares hematopoietic (stem) cell transplantation (HCT) using mismatched related donors (haploidentical \[haplo\]) versus matched unrelated donors (MUD) in treating children, adolescents, and young adults with acute leukemia or myelodysplastic syndrome (MDS). HCT is considered standard of care treatment for patients with high-risk acute leukemia and MDS. In HCT, patients are given very high doses of chemotherapy and/or radiation therapy, which is intended to kill cancer cells that may be resistant to more standard doses of chemotherapy; unfortunately, this also destroys the normal cells in the bone marrow, including stem cells. After the treatment, patients must have a healthy supply of stem cells reintroduced or transplanted. The transplanted cells then reestablish the blood cell production process in the bone marrow. The healthy stem cells may come from the blood or bone marrow of a related or unrelated donor. If patients do not have a matched related donor, doctors do not know what the next best donor choice is. This trial may help researchers understand whether a haplo related donor or a MUD HCT for children with acute leukemia or MDS is better or if there is no difference at all.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Victor Aquino
ALL
6 Months to 21 Years old
PHASE3
NCT05457556
STU-2024-0214
Inclusion Criteria:
* PATIENT INCLUSION CRITERIA FOR ENROLLMENT:
* 6 months to \< 22 years at enrollment
* Diagnosed with ALL, AML, or MDS or mixed phenotype acute leukemia (MPAL) for which an allogeneic hematopoietic stem cell transplant is indicated. Complete Remission (CR) status will not be confirmed at the time of enrollment. CR as defined in these sections is required to proceed with the actual HCT treatment plan
* Has not received a prior allogeneic hematopoietic stem cell transplant
* Does not have a suitable human leukocyte antigen (HLA)-matched sibling donor available for stem cell donation
* Has an eligible haploidentical related family donor based on at least intermediate resolution HLA typing
* Patients who also have an eligible 8/8 MUD adult donor based on confirmatory high resolution HLA typing are eligible for randomization to Arm A or Arm B.
* Patients who do not have an eligible MUD donor are eligible for enrollment to Arm C
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
* Co-Enrollment on other trials
* Patients will not be excluded from enrollment on this study if already enrolled on other protocols for treatment of high risk and/or relapsed ALL, AML, MPAL and MDS. This is including, but not limited to, COG AAML1831, COG AALL1821, the EndRAD Trial, as well as local institutional trials. We will collect information on all co-enrollments
* Patients will not be excluded from enrollment on this study if receiving immunotherapy prior to transplant as a way to achieve remission and bridge to transplant. This includes chimeric antigen receptor (CAR) T cell therapy and other immunotherapies
* PATIENT INCLUSION CRITERIA TO PROCEED TO HCT:
* Karnofsky Index or Lansky Play-Performance Scale \>= 60 on pre-transplant evaluation. Karnofsky scores must be used for patients \>= 16 years of age and Lansky scores for patients =\< 16 years of age (within 4 weeks of starting therapy)
* A serum creatinine based on age/gender as follows:
6 months to \< 1 year: 0.5 mg/dL (Male); 0.5 mg/dL (Female)
• to \< 2 years: 0.6 mg/dL (Male); 0.6 mg/dL (Female)
• to \< 6 years: 0.8 mg/dL (Male); 0.8 mg/dL (Female) 6 to \< 10 years: 1 mg/dL (Male); 1 mg/dL (Female) 10 to \< 13 years: 1.2 mg/dL (Male); 1.2 mg/dL (Female) 13 to \< 16 years: 1.5 mg/dL (Male); 1.4 mg/dL (Female) \>= 16 years: 1.7 mg/dL (Male); 1.4 mg/dL (Female) * OR * A 24 hour urine Creatinine clearance \>= 60 mL/min/1.73 m\^2 * OR * A glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility * Serum glutamic-oxaloacetic transaminase (SGOT) aspartate aminotransferase \[AST\] or serum glutamate pyruvate transaminase (SGPT) aminotransferase \[ALT\] \< 5 x upper limit of normal (ULN) for age * Total bilirubin \< 2.5 mg/dL, unless attributable to Gilbert's Syndrome * Shortening fraction of \>= 27% by echocardiogram or radionuclide scan (MUGA) * OR * Ejection fraction of \>= 50% by echocardiogram or radionuclide scan (MUGA), choice of test according to local standard of care * Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and corrected carbon monoxide diffusing capability (DLCO) must all be \>= 50% of predicted by pulmonary function tests (PFTs). * For children who are unable to perform for PFTs (e.g., due to age or developmental delay), the criteria are: no evidence of dyspnea at rest, oxygen (O2) saturation (Sat) \> 92% on room air by pulse oximetry, not on supplemental O2 at rest, and not on supplemental O2 at rest * MPAL in first complete remission (CR1) for whom transplant is indicated. Examples include those patients who are poorly responsive to ALL therapy (end of induction failure( IF-MPAL) to ALL induction (see IF-MPAL note below), end of induction MRD ≥ 5% or end-of-consolidation MRD \> 0.01%), as well as patients treated with AML therapy * IF-MPAL: additional criterion for Induction failure for MPAL ONLY as per ALL1732: * An increasing number of circulating leukemia cells on 3 or more consecutive CBCs obtained at daily or longer intervals following day 8 of Induction therapy and prior to day 29 with confirmation by flow cytometry OR development of new sites of extramedullary disease, or other laboratory or clinical evidence of refractory disease or progression prior to the end of Induction evaluation (note that residual testicular disease at the end of Induction is an exception) * MPAL in \> second complete remission (CR2) * ALL high-risk in CR1 for whom transplant is indicated. Examples include: induction failure, treatment failure as per minimal residual disease by flow cytometry \> 0.01% after consolidation and not eligible for AALL1721 or AALL1721 not available/unwilling to enroll, hypodiploidy (\< 44 chromosomes) with MRD+ \> 0.01% after induction, persistent or recurrent cytogenetic or molecular evidence of disease during therapy requiring additional therapy after induction to achieve remission (e.g. persistent molecular BCR-ABL positivity), T cell ALL with persistent MRD \> 0.01% after consolidation. * ALL in CR2 for whom transplant is indicated. Examples include: B-cell: early (=\< 36 months from initiation of therapy) bone marrow (BM) relapse, late BM relapse (\>= 36 months) with MRD \>= 0.1% by flow cytometry after first re-induction therapy; T or B-cell: early (\< 18 months) isolated extramedullary (IEM), late (\>= 18 months) IEM, end-Block 1 MRD \>= 0.1%; T-cell or Philadelphia chromosome positive (Ph+): BM relapse at any time * ALL in \>= third complete remission (CR3) * Patients treated with chimeric antigen receptor T-cells (CART) cells for whom transplant is indicated. Examples include: transplant for consolidation of CART, loss of CART persistence and/or B cell aplasia \< 6 months from infusion or have other evidence (e.g., MRD+) that transplant is indicated to prevent relapse * AML in CR1 for whom transplant is indicated. Examples include those deemed high risk for relapse as described in AAML1831: * FLT3/ITD+ with allelic ratio \> 0.1 without bZIP CEBPA, NPM1 * FLT3/ITD+ with allelic ratio \> 0.1 with concurrent bZIP CEBPA or NPM1 and with evidence of residual AML (MRD \>= 0.05%) at end of Induction * Presence of RAM phenotype or unfavorable prognostic markers (other than FLT3/ITD) per cytogenetics, fluorescence in situ hybridization (FISH), next generation sequencing (NGS) results, regardless of favorable genetic markers, MRD status or FLT3/ITD mutation status * AML without favorable or unfavorable cytogenetic or molecular features but with evidence of residual AML (MRD \>= 0.05%) at end of Induction * Presence of a non-ITD FLT3 activating mutation and positive MRD (\>= 0.05%) at end of Induction 1 regardless of presence of favorable genetic markers. * AML in \>= CR2 * MDS with \< 5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation * Complete remission (CR) is defined as \< 5% blasts by morphology and flow cytometry (if available) on the pre-transplant bone marrow evaluation with minimum sustained absolute neutrophil count (ANC) of 300 cells/microliter for 1 week or ANC \> 500 cells/microliter. We will be collecting data from all approaches to MRD evaluation performed including NGS and polymerase chain reaction (PCR). It is strongly recommended that MPAL be evaluated using multidimensional flow cytometry and/or (KMT2Ar) qt PCR. It is strongly recommended that MPAL be evaluated using multidimensional flow cytometry and/or (KMT2Ar) qt PCR * DONOR ELIGIBILITY CRITERIA: * Matched Unrelated Donors: Unrelated donor candidates must be matched at high resolution at a minimum of 8/8 alleles (HLA-A, -B, -C, -DRB1). One-antigen HLA mismatches are not permitted. HLA matching of additional alleles is recommended according to National Marrow Donor Program (NMDP) guidelines, but will be at the discretion of local centers * Haploidentical Matched Family Members: * Minimum match level full haploidentical (at least 5/10; HLA-A, -B, -C, -DRB1, -DQB1 alleles). The following issues (in no particular order) should be considered in choosing a haploidentical donor: * Absent or low patient donor-specific antibodies (DSA) * Mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be \< 2000. Donors with higher levels are not eligible. * If a screening assay against pooled HLA antigens is used, positive results must be followed with specificity testing using a single antigen assay. The MFI must be \< 2000 unless the laboratory has validated higher threshold values for reactivity for HLA antigens (such as HLA-C, -DQ, and -DP), that may be enhanced in concentration on the single antigen assays. Donor anti- recipient antibodies are of unknown clinical significance and do not need to be sent or reported. * Consult with Study Chair for the clinical significance of any recipient anti-donor HLA antibody. * If centers are unable to perform this type of testing, please contact the Study Chair to make arrangements for testing. * If killer immunoglobulin testing (KIR) is performed: KIR status by mismatch, KIR-B, or KIR content criteria can be used according to institutional guidelines. * ABO compatibility (in order of priority): * Compatible or minor ABO incompatibility * Major ABO incompatibility * CMV serostatus: * For a CMV seronegative recipient: the priority is to use a CMV seronegative donor when feasible * For a CMV seropositive recipient: the priority is to use a CMV seropositive donor when feasible * Age: younger donors including siblings/half-siblings, and second degree relatives (aunts, uncles, cousins) are recommended, even if \< 18 years * Size and vascular access appropriate by center standard for peripheral blood stem cell (PBSC) collection if needed * Haploidentical matched family members: screened by center health screens and found to be eligible * Unrelated donors: meet eligibility criteria as defined by the NMDP or other unrelated donor registries. If the donor does not meet the registry eligibility criteria but an acceptable eligibility waiver is completed and signed per registry guidelines, the donor will be considered eligible for this study * Human immunodeficiency virus (HIV) negative * Not pregnant * MUD donors and post-transplant cyclophosphamide haplo donors should be asked to provide BM. If donors refuse and other donors are not available, PBSC is allowed. TCR-alpha beta/CD19 depleted haplo donors must agree to donate PBSC * Must give informed consent: * Haploidentical matched family members: Institution standard of care donor consent and Protocol-specific Donor Consent for Optional Studies * Unrelated donors: standard NMDP Unrelated Donor Consent
Exclusion Criteria:
* PATIENT EXCLUSION CRITERIA FOR ENROLLMENT:
* Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL/MPAL with known poor outcomes because of sensitivity to alkylator therapy and/or TBI are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc). Patients with Downs syndrome because of increased toxicity with intensive conditioning regimens.
* Patients with any obvious contraindication to myeloablative HCT at the time of enrollment
* Female patients who are pregnant are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* PATIENT EXCLUSION CRITERIA TO PROCEED TO HCT:
* Patients with uncontrolled fungal, bacterial, viral, or parasitic infections are excluded. Patients with history of fungal disease during chemotherapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by computed tomography (CT) evaluation
* Patients with active central nervous system (CNS) leukemia or any other active site of extramedullary disease at the time of initiation of the conditioning regimen are not permitted.
* Note: Those with prior history of CNS or extramedullary disease, but with no active disease at the time of pre-transplant workup, are eligible
* Pregnant or breastfeeding females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, DRUG: Busulfan, DRUG: Cyclophosphamide, PROCEDURE: Echocardiography, DRUG: Fludarabine, PROCEDURE: Haploidentical Hematopoietic Cell Transplantation, BIOLOGICAL: Lapine T-Lymphocyte Immune Globulin, PROCEDURE: Lumbar Puncture, PROCEDURE: Matched Unrelated Donor Hematopoietic Cell Transplantation, DRUG: Melphalan, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Mycophenolate Mofetil, PROCEDURE: Myeloablative Conditioning, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, BIOLOGICAL: Rituximab, PROCEDURE: T-Cell Depletion Therapy, DRUG: Tacrolimus, DRUG: Thiotepa, RADIATION: Total-Body Irradiation
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Leukemia, Not Otherwise Specified, Leukemia, Other
Children’s Health
Peanut Sublingual Immunotherapy (SLIT)-Tablet for Treatment of Peanut Allergy
This clinical research study investigates the safety, tolerability and efficacy of a peanut SLIT-tablet in adults, adolescents, and children with peanut allergy.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kaylee.Lirely@Childrens.com
John Bird
ALL
4 Years to 65 Years old
PHASE1
NCT05440643
STU-2024-0597
KEY INCLUSION CRITERIA:
Subjects are eligible to be included in the trial only if all the following criteria apply:
* Part 1: Male or female aged 12 through 65 years (inclusive) on the day of enrollment Part 2: Male or female aged 4 through 65 years (inclusive) on the day of enrollment Part 3: Male or female aged 4 through 65 years (inclusive) on the day of randomization
* Documented clinical history of an IgE-mediated allergic reaction towards peanut- containing food
* Peanut-specific serum IgE ≥ 0.7 kU/L at screening measured at central laboratory
* Skin prick test to peanut ≥ 5 mm at screening
* Cohorts 1-8: Experience dose-limiting symptoms at the 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC Cohorts 9-10: Experience dose-limiting symptoms at the 1 mg or 3 mg challenge dose of peanut protein on the screening DBPCFC Part 3: Experience dose-limiting symptoms at the 3 mg, 10 mg, 30 mg or 100 mg challenge dose of peanut protein on screening DBPCFC
KEY EXCLUSION CRITERIA:
Subjects are excluded from the trial if any of the following criteria apply:
* Diagnosis or history of eosinophilic esophagitis
* Uncontrolled asthma as defined by the Asthma Control Test questionnaire with a score of 19 or below at enrollment (subjects with a diagnosis of asthma only)
* All subjects ≥ 5 years old with FEV1 or PEFR \< 70% of predicted value at enrollment Subjects 4 years old with a history of recurrent wheeze requiring inhaled corticosteroids for 2 consecutive weeks or more within 3 months prior to enrollment
* Up-dosing with any allergy immunotherapy product. Maintenance dose of any subcutaneous immunotherapy product other than peanut is allowed
* History of peanut oral immunotherapy within the last 12 months prior to visit 1
* Chronic or acute oral inflammation at enrollment
* History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
* Currently using any prohibited medication on the list of prohibited medication
* Part 1 and 2: Allergic symptoms in reaction to the placebo part of the screening DBPCFC Part 3: Dose-limiting allergic symptoms in reaction to the placebo part of the screening DBPCFC
* History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 60 days of the screening DBPCFC
* Part 1 and 2: Asthma according to below criteria:
* Severe asthma as per the current GINA guidelines
* Uncontrolled or poorly controlled asthma as per the current GINA guidelines
* Asthma that requires more than a daily dose above 800 µg of inhaled budesonide (or clinically comparable inhaled corticosteroids)
* History of 2 or more systemic corticosteroid courses within 6 months of screening
* Prior intubation/mechanical ventilation for asthma
* Emergency room visit or hospitalization for asthma in the 12 months prior to screening
* Any history of a life-threatening asthma attack
* Part 3: Asthma fulfilling the below criteria:
* History of 2 or more systemic corticosteroid courses within 6 months of screening
* Prior intubation/mechanical ventilation for asthma
* Emergency room visit or hospitalization for asthma in the 12 months prior to screening
* Any history of a life-threatening asthma attack
* (US only) Severe asthma as per the current GINA guidelines
* (US only) Uncontrolled or poorly controlled asthma as per the current GINA guidelines
* (US only) Asthma that requires more than a daily maintenance dose above 800 μg of inhaled budesonide (or clinically comparable inhaled corticosteroids)
BIOLOGICAL: Peanut SLIT-tablet, OTHER: Placebo
Peanut Allergy
Peanut allergy, Children, Adolescent, Adult
Children’s Health
Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) (ICECAP)
This is a multicenter trial to establish the efficacy of cooling and the optimal duration of induced hypothermia for neuroprotection in pediatric comatose survivors of cardiac arrest. The study team hypothesizes that longer durations of cooling may improve either the proportion of children that attain a good neurobehavioral recovery or may result in better recovery among the proportion already categorized as having a good outcome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kirstie.LeDoux@UTSouthwestern.edu
Joshua Wolovits
All
2 Days to 17 Years old
N/A
NCT05376267
STU-2022-0800
Inclusion criteria:
• Age 2 days to < 18 years with corrected gestational age of at least 38 weeks
• Chest compressions for at least 2 minutes
• Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
• Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
• Definitive temperature control device initiated
• Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
• Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours Exclusion criteria:
• Glasgow Coma Motor Score (GCMS) = 6
• LAR does not speak English or Spanish
• Duration of Cardiopulmonary Resuscitation (CPR) > 60 minutes
• Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
• Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
• Pre-existing terminal illness, unlikely to survive to one year
• Cardiac arrest associated with brain, thoracic, or abdominal trauma
• Active and refractory severe bleeding prior to randomization
• Extensive burns or skin lesions incompatible with surface cooling
• Planned early withdrawal of life support before 120 hours
• Sickle cell anemia
• Pre-existing cryoglobulinemia
• Non-fatal drowning in ice covered water
• Central nervous system tumor with ongoing chemotherapy
• Previous enrollment in P-ICECAP trial
• Prisoner
• Chronic hypothermia
• New post-cardiac arrest diabetes insipidus
• Pregnancy
• Age 2 days to < 18 years with corrected gestational age of at least 38 weeks
• Chest compressions for at least 2 minutes
• Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
• Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
• Definitive temperature control device initiated
• Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
• Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours Exclusion criteria:
• Glasgow Coma Motor Score (GCMS) = 6
• LAR does not speak English or Spanish
• Duration of Cardiopulmonary Resuscitation (CPR) > 60 minutes
• Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
• Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
• Pre-existing terminal illness, unlikely to survive to one year
• Cardiac arrest associated with brain, thoracic, or abdominal trauma
• Active and refractory severe bleeding prior to randomization
• Extensive burns or skin lesions incompatible with surface cooling
• Planned early withdrawal of life support before 120 hours
• Sickle cell anemia
• Pre-existing cryoglobulinemia
• Non-fatal drowning in ice covered water
• Central nervous system tumor with ongoing chemotherapy
• Previous enrollment in P-ICECAP trial
• Prisoner
• Chronic hypothermia
• New post-cardiac arrest diabetes insipidus
• Pregnancy
Device: Therapeutic Hypothermia
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma, Pediatric
Children’s Health
Phase 2/3 Adaptive Study of VX-147 in Adult and Pediatric Participants With APOL1- Mediated Proteinuric Kidney Disease (AMPLITUDE)
The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of VX-147 in adult and pediatric participants with apolipoprotein L1 (APOL1)-mediated proteinuric kidney disease.
Call 214-648-5005
studyfinder@utsouthwestern.edu, ZHENGNAN.WANG@UTSouthwestern.edu
Robert Toto
ALL
10 Years to 65 Years old
PHASE2
NCT05312879
STU-2023-1084
Key
Inclusion Criteria:
* APOL1 genotype of G1/G1, G2/G2, or G1/G2
* Proteinuric kidney disease
Key Exclusion Criteria:
* Solid organ or bone marrow transplant
* Uncontrolled hypertension
* History of diabetes mellitus
* Known underlying cause of kidney disease including but not limited to sickle cell disease
Other protocol defined Inclusion/Exclusion criteria apply DRUG: VX-147, DRUG: Placebo
Proteinuric Kidney Disease
UT Southwestern; Parkland Health & Hospital System
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back (relapsed) or do not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, seen with some aggressive cancers that are typically hard to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Months and over
PHASE1
NCT05286801
STU-2022-0879
Inclusion Criteria:
* Patients must be \>= 12 months of age at the time of study enrollment. For part A, patients must be \< 18 years old at enrollment. For part B, there is no upper age limit
* The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients \< 18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
* Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:
* Renal medullary carcinoma
* Malignant rhabdoid tumor (extra-CNS)
* Atypical teratoid rhabdoid tumor (CNS)
* Poorly differentiated chordoma
* Epithelioid sarcoma
* Other SMARCB1 or SMARCA4 deficient tumors
* Note: Molecular studies will only be used if IHC is equivocal or cannot be performed. Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
* Part A: Patients must have either measurable or evaluable disease Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors
* Note: See protocol for specific exclusion for patients with CNS primary or metastatic disease
* Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of \>= 50). Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation \[TBI\]):
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* External radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 90 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have had prior TIGIT targeting therapy
* Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
* Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
* Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha \[TNF-alpha\] agents) must have concluded \>= 14 days prior to study enrollment
* For patients with solid tumors without known bone marrow involvement
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (must be performed within 7 days prior to enrollment)
* For patients with solid tumors without known bone marrow involvement
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
* A creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
* Age; Maximum Serum Creatinine (mg/dL)
* 1 to \< 2 years; Male: 0.6; Female: 0.6
* 2 to \< 6 years; Male: 0.8; Female: 0.8
* 6 to \< 10 years; Male: 1; Female: 1
* 10 to \< 13 years; Male: 1.2; Female: 1.2
* 13 to \< 16 years; Male: 1.5; Female: 1.4
* \>= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (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) (must be performed within 7 days prior to enrollment)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
* Patients with known Gilbert disease: Total bilirubin =\< 3 x ULN
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (must be performed within 7 days prior to enrollment)
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] v5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* International normalized ratio (INR) =\< 1.5 (must be performed within 7 days prior to enrollment)
* Serum amylase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Serum lipase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Grade 1 or lower calcium level
* Note: can have history of hypercalcemia as long as controlled and asymptomatic
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in female patients of childbearing potential. Female patients of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
* It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
* Concomitant medications:
* Corticosteroids:
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
* Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
* Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
* Patients who have undergone allogeneic bone marrow or allogeneic cell transplant are not eligible
* Patients with CNS metastases from non-CNS primary tumors are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS.
* Patients with primary CNS tumors (including ATRT) with involvement of the brainstem are not eligible. Note: Patients with ATRT with M0-M4 disease without involvement of the brain stem are allowed to participate
* Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
* Patients who have active immune deficiency are not eligible
* Patients who have known active tuberculosis are not eligible
* Hepatitis B or C infection:
* Patients \< 18 years old at enrollment, who have known hepatitis B or C
* Patients \>= 18 years old at enrollment with:
* Positive hepatitis B surface antigen (HBsAg), OR
* Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \>= 500 IU/mL, OR
* Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
* Note: For adults (\>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (\>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
* Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
* Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load
* Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
* Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
* Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
* Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* 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: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Fludeoxyglucose F-18, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Tiragolumab, PROCEDURE: X-Ray Imaging
Atypical Teratoid/Rhabdoid Tumor, Epithelioid Sarcoma, Kidney Medullary Carcinoma, Malignant Solid Neoplasm, Poorly Differentiated Chordoma, Recurrent Atypical Teratoid/Rhabdoid Tumor, Recurrent Chordoma, Recurrent Epithelioid Sarcoma, Recurrent Kidney Medullary Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Rhabdoid Tumor, Refractory Atypical Teratoid/Rhabdoid Tumor, Refractory Chordoma, Refractory Epithelioid Sarcoma, Refractory Kidney Medullary Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Rhabdoid Tumor, Rhabdoid Tumor, Bones and Joints, Soft Tissue
Children’s Health
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
up to 21 Years old
PHASE3
NCT05304585
STU-2022-0692
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial).
* Patients must be =\< 21 years at the time of enrollment.
* Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients.
* All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed.
* Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease.
* Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease.
* Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients \>= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging.
* Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors.
* Clinically or radiographically enlarged nodes must be sampled for histologic evaluation.
* Patients must have a Lansky (for patients =\< 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of \>= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (within 7 days prior to enrollment).
* Platelet count \>= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender 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)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
* If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x 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.
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L
* If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x 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
* 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:
* Patients who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
* Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy.
* Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment.
* Patients unable to undergo radiation therapy, if necessary, as specified in the protocol.
* Evidence of uncontrolled infection.
* 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: Biopsy, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, PROCEDURE: Magnetic Resonance Elastography, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy, DRUG: Vincristine
Embryonal Rhabdomyosarcoma, Fusion-Negative Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Sarcoma
Children’s Health
Study of the Adverse Events and Change in Disease State of Pediatric Participants (and Young Adults Between the Ages of 18-25) With Relapsed/Refractory Aggressive Mature B-cell Neoplasms Receiving Subcutaneous (SC) Injections of Epcoritamab
The most common types of mature B-cell lymphomas (MBLs) in children are Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Initial treatment cures 90% - 95% of children with these malignancies, leaving a very small population of relapsed/refractory disease with a poor prognosis. The purpose of this study is to assess the safety and tolerability of epcoritamab in pediatric participants with relapsed/refractory aggressive mature B-cell neoplasms and young adult participants with Burkitt's or Burkitt-like lymphoma/leukemia. Adverse events and change in disease activity will be assessed. Epcoritamab is an investigational drug being developed for the treatment of relapsed/refractory aggressive mature B-cell neoplasms. Participants will receive subcutaneous (SC) of epcoritamab. Approximately 15 pediatric participants with a diagnosis of relapsed/refractory aggressive mature B-cell neoplasms and and young adult participants, ages of 18-25, with a diagnosis of Burkitt's or Burkitt-like lymphoma/leukemia will be enrolled at 50 sites globally. Participants will receive subcutaneous epcoritamab in 28-day cycles. Participants will be followed for a minimum of 3 years after enrollment. 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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
1 Year to 25 Years old
PHASE1
NCT05206357
STU-2022-1118
Inclusion Criteria:
* Participants \>= 1 and \< 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma (DLBCL), or other aggressive mature (CD20+) B-cell lymphomas. Participants up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible.
* Disease pathologically confirmed (tumor tissue) by local testing.
* Relapsed or primary refractory disease meeting any of the following criteria:
* Progressive disease at any time during second-line chemoimmunotherapy (CIT).
* Best response of stable disease (SD) after a minimum of 2 cycles of second-line CIT.
* Best response of partial response (PR) after a minimum of 3 cycles of second-line CIT.
* Complete Response (CR) after a minimum of 3 cycles of second-line CIT therapy but unfit or ineligible for consolidation with cell therapy.
* Not in CR and unable to initiate or tolerate (i.e., must discontinue) second-line CIT.
* Have received cell therapy (allogeneic or autologous transplant or chimeric antigen receptor T-cell (CAR-T) therapy) as consolidation but have not obtained or maintained a CR.
* Recovery from toxic effects of prior chemoimmunotherapy.
* Performance status by Lansky (\< 16 years old at evaluation) or Karnofsky (\>= 16 years old at evaluation) score \>= 50 or Eastern Cooperative Oncology Group (ECOG) score \<= 2 .
* Adequate bone marrow, hepatic, and renal function.
Exclusion Criteria:
* Known central nervous system (CNS) involvement by lymphoma at screening as confirmed by screening magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) brain scans (participants with evidence of CNS disease only in the cerebrospinal fluid (CSF) will be eligible).
* Other malignancy requiring therapy.
* Currently receiving anti-cancer therapy, including chemotherapy (excluding intrathecal therapy), radiotherapy, small molecules, monoclonal antibodies, cell therapy, or other investigational agents. DRUG: Epcoritamab
Non-hodgkin Lymphoma, Lymphoma
Non-hodgkin Lymphoma, ABBV-GMAB-3013, Epcoritamab, Burkitt's or Burkitt-like Lymphoma/Leukemia, Diffuse Large B-cell Lymphoma, Aggressive Mature (CD20+) B-cell Lymphoma, Cancer, Relapsed/Refractory Aggressive Mature B-cell Neoplasms, EPCORE
Children’s Health
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
This phase III trial compares the effect of open thoracic surgery (thoracotomy) to thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery is a type of surgery done through a single larger incision (like a large cut) that goes between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest surgery where the doctor makes several small incisions and uses a small camera to help with removing the cancer. This trial is being done evaluate the two different surgery methods for patients with osteosarcoma that has spread to the lung to find out which is better.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
up to 50 Years old
PHASE3
NCT05235165
STU-2022-0187
Inclusion Criteria:
* Patients must be \< 50 years at the time of enrollment.
* Patients must have =\< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being \>= 3 mm and all of which must be =\< 3 cm size.
* Note: Patient must have eligibility confirmed by rapid central imaging review.
* Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
* Patients must have a histological diagnosis of osteosarcoma.
* Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
* Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
* Newly diagnosed patients must be receiving or recently completed (within 60 days) systemic therapy considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
* Patients at time of 1st recurrence must have completed systemic therapy for their initial primary tumor, considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
Exclusion Criteria:
* Patients with unresectable primary tumor.
* Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
* Patients with chest wall or mediastinal based metastatic lesions, or with significant pleural effusion.
* Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
* Patients with evidence of extrapulmonary metastatic disease.
* Patients who received therapeutic pulmonary surgery for lung metastasis prior to enrollment.
* 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: Computed Tomography, OTHER: Questionnaire Administration, PROCEDURE: Thoracoscopy, PROCEDURE: Thoracotomy
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma, Bones and Joints, Lung/Thoracic
Children’s Health
Comparison of Methods of Pulmonary Blood Flow Augmentation in Neonates: Shunt Versus Stent (The COMPASS Trial) (COMPASS)
COMPASS is a prospective multicenter randomized interventional trial. Participants with ductal-dependent pulmonary blood flow will be randomized to receive either a systemic-to-pulmonary artery shunt or ductal artery stent. Block randomization will be performed by center and by single vs. two ventricle status. Participants will be followed through the first year of life.
Call 214-648-5005
studyfinder@utsouthwestern.edu, madison.munson@childrens.com
Surendranath Veeram Reddy
ALL
1 Day to 30 Days old
NA
NCT05268094
STU-2023-0190
Inclusion Criteria:
• Neonates with Congenital Heart Disease (CHD) and ductal-dependent pulmonary blood flow requiring only a stable source of pulmonary blood flow as the initial palliation, for whom the clinical decision is made at the enrolling center that this is best achieved by either DAS or SPS.
• Age ≤ 30 days at time of index procedure (DAS or SPS).
Exclusion Criteria:
* 1. Any patient for whom the clinical decision at the enrolling center is that an initial intervention other than DAS or SPS is indicated (e.g., Right Ventricle-Pulmonary Artery (RV-PA) conduit, Right Ventricular Outflow Tract (RVOT) stent, primary complete anatomic repair, etc.).
• Pulmonary Atresia with Intact Ventricular Septum (PA/IVS) where Right Ventricle (RV) decompression is planned.
• Presence of MAPCAs: defined as an aortopulmonary collateral that is expected to require unifocalization.
• Non-confluent Pulmonary Arteries (i.e., isolated Pulmonary Artery (PA) of ductal origin).
• Acutely jeopardized branch Pulmonary Arteries (\>75% narrowing of proximal PA based on screening cross sectional imaging \[Computed Tomography Angiography (CTA) or cardiovascular Magnetic Resonance (cMR)\]).
• Bilateral Patent Ductus Arteriosis (PDA). 7. Patient who, at the time of enrollment, is deemed not to be a candidate for eventual Glenn or Complete Surgical Repair (CSR) for any reason.
• Birth weight \<2.0 kg. 9. Gestational age \<34 weeks at birth. 10. Patient for whom additional intervention is expected concomitant with, or prior to, DAS or SPS (e.g., atrial septostomy, aortic arch intervention, or RV outflow tract intervention) - except for branch PA arterioplasty or stent/balloon angioplasty.
• Major co-morbidities which, in the opinion of the investigator, would negatively alter expected 1-year survival (e.g., intracranial hemorrhage, renal failure, etc.).
• Specific known genetic anomaly which, in the opinion of the investigator, would be expected to significantly alter clinical course in the first year of life (e.g., Trisomy 13/18, CHARGE, VACTERL).
• Patient who does not plan to return to the enrolling center or another participating center for Glenn/CSR.
DEVICE: Ductal Arterial Stent, PROCEDURE: Systemic-to-Pulmonary Artery Shunt
Congenital Heart Disease in Children
Congenital Heart Disease, Ductal Dependent Pulmonary Blood Flow, Ductal Artery Shunt, Systemic-to-Pulmonary Artery Shunt
Children’s Health
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin \[GO\]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
29 Days to 21 Years old
PHASE3
NCT05183035
STU-2022-0725
Inclusion Criteria
* Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
* Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
* Participants must have one of the following:
* Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score) * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]) * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving another investigational drug (GO is not considered investigational in this study). * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * No known human immunodeficiency virus (HIV) infection. * Post menarchal female participants with positive pregnancy test. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4 * to participants with history of VOD/SOS grade 3 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score) * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]) * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving another investigational drug (GO is not considered investigational in this study). * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * No known human immunodeficiency virus (HIV) infection. * Post menarchal female participants with positive pregnancy test. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4 * to participants with history of VOD/SOS grade 3 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
DRUG: Fludarabine, DRUG: Cytarabine, DRUG: Gemtuzumab Ozogamicin, DRUG: Azacitidine, DRUG: Venetoclax
Acute Myeloid Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
Venetoclax, Gemtuzumab Ozogamicin, Fludarabine, Cytarabine, Relapsed refractory, Azacitidine
Children’s Health
Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas (POPLAR-NF2)
This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
All
12 Years and over
Phase 2/Phase 3
NCT05130866
STU-2021-1151
Inclusion Criteria:
• ≥12 years of age and weighing at least 40 kg
• Progressive meningioma that is amenable to volumetric analysis
• Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
• Adequate bone marrow function
• Has provided written informed consent/assent to participate in the study
Exclusion Criteria:
• Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
• Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening.
• Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
• History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
• Received another investigational drug within 30 days prior to screening
• Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.
Drug: REC-2282, Drug: Placebo
Neurofibromatosis Type 2, Brain and Nervous System
Neurofibromatosis Type 2, Neurofibromatosis Type II
UT Southwestern; Children’s Health
Study to Evaluate the Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects with PL (METRE-PL)
This is a Phase III, double-blind, placebo-controlled, safety and efficacy study of daily SC metreleptin in subjects with Partial Lipodystrophy.
Call 214-648-5005
studyfinder@utsouthwestern.edu, CHANDNA.VASANDANI@UTSouthwestern.edu
Abhimanyu Garg
ALL
12 Years and over
PHASE3
NCT05164341
STU-2021-1141
Inclusion Criteria:
* Diagnosis of Familial Partial Lipodystrophy (FPLD)
* Subjects with poor metabolic control defined as:
HbA1c ≥7% (at Visit 1 and Visit 3) and/or Fasting TGs ≥500 mg/dL (5.65 mmol/L, at Visit 1 and Visit 3)
* Patients should be receiving optimized stable therapy
Exclusion Criteria:
* Previous treatment with metreleptin
* Leptin levels \>20.0 ng/mL
* Acquired or radiation induced partial lipodystrophy (APL)
Other protocol defined inclusion/exclusion criteria apply DRUG: metreleptin, DRUG: Placebo
Partial Lipodystrophy
metreleptin
UT Southwestern
A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy (HOPE-3)
HOPE-3 is a two cohort, Phase 3, multi-center, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of a cell therapy called CAP-1002 in study participants with Duchenne muscular dystrophy (DMD) and impaired skeletal muscle function. Non-ambulatory and ambulatory boys and young men who meet eligibility criteria will be randomly assigned to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during the first 12-months of the study. All participants will be eligible to receive 4 doses of CAP-1002 for an additional 12 months as part of an open-label extended assessment period.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Tammy.Ramm@UTSouthwestern.edu
Susan Iannaccone
MALE
10 Years and over
PHASE3
NCT05126758
STU-2022-0124
Inclusion Criteria:
• Male subjects at least 10 years of age at time of consent who are willing and able to provide informed consent to participate in the trial if ≥ 18 years of age or assent with parental or guardian informed consent if \< 18 years of age. If a third-party caregiver is involved, they must provide informed consent.
• Diagnosis of DMD based on clinical and phenotypic manifestations consistent with DMD (e.g., family history of DMD, elevated creatine kinase, dystrophin muscle biopsy, calf pseudohypertrophy, history of Gowers' sign, and gait impairment before 7 years of age) as confirmed by the Investigator.
• Confirmatory genetic testing performed to have reached a diagnosis of DMD at any time in the past or currently performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory or equivalent.
• Performance of the Upper Limb test (PUL) entry item scores 2-6 and total PUL score less than or equal to 40. For Cohort A only: enrollment of patients with PUL entry score 6, Exon 44 skipping amenable, and/or Exon 3 through 7 deletions will be capped at no more than 10% of the total study population (approximately 6 patients with these characteristics).
• Reduced ability to walk/run (if ambulatory): subjects must take more than 10 seconds for the 10-meter walk/run (i.e., velocity \< 1 meter/second).
• If non-ambulatory, loss of independent ambulation between 10th and 18th year birthday (standing unassisted or ability to take, at most, several steps independently is not considered ambulation). Subjects who are considered non-ambulatory between the ages of 9 and10 may be enrolled with prior approval from the sponsor.
• Receiving standard of care therapy at an experienced, multidisciplinary DMD center as evidenced by regular cardiac and pulmonary monitoring, systemic glucocorticoid treatment, and at-home range of motion exercises.
• Treatment with systemic glucocorticoids for at least 12 months and at a stable dose at least 6 months prior to study participation, except for either weight-based dose adjustment or a decrease in steroid dose of ≤ 10% for toxicity. For patients on chronic deflazacort, treatment with an equivalent dose of prednisone or prednisolone for a period of ≤ 30 days to bridge lack of availability of deflazacort during the 6 months prior to randomization is acceptable.
• Current and up-to-date immunizations according to children and adolescent Centers for Disease Control and Prevention immunization schedule at the discretion of the Investigator.
• Adequate venous access for parenteral IP infusions and routine blood collection.
• Assessed by the Investigator as willing and able to comply with the requirements of the trial.
• Sexually active subjects and their partners who are fertile must agree to use effective method(s) of contraception.
Exclusion Criteria:
• Left ventricular ejection fraction (LVEF) less than or equal to 35% prior to randomization.
• Elbow-flexion contractures \> 30° in both extremities.
• Body mass index (BMI) \> 45.
• Percent predicted forced vital capacity (FVC%) \< 35% within 6 months prior to randomization.
• Inability to perform consistent PUL 2.0 measurement within ± 2 points without shoulder domain or within ± 3 points with shoulder domain during paired testing at screening.
• Risk of near-term respiratory decompensation in the judgment of the Investigator, or the need for initiation of day and night non-invasive ventilator support as defined by serum bicarbonate ≥ 29 mmol/L at screening.
• History of non DMD-related chronic respiratory disease requiring ongoing or intermittent treatment, including, but not limited to, asthma, bronchitis, and tuberculosis.
• Acute respiratory illness within 30 days prior to screening and during screening.
• Initiation of nocturnal non-invasive ventilation within 30 days prior to screening.
• Planned or anticipated thoracic or spinal surgery within the 6 months following randomization.
• Planned or anticipated lower extremity surgery within the 6 months following randomization, if ambulatory.
• Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products.
• Initiation of treatment with metformin or insulin within 3 months prior to randomization.
• Initiation of treatment with an FDA-approved exon skipping therapy for the treatment of DMD and/or non-weight based adjustments within 12 months prior to randomization.
• Treatment with human growth hormone within 3 months prior to randomization, unless on a stable dose allowing for weight-based dose adjustments (as determined by the site Investigator) for at least 24 months prior to randomization.
• Treatment with a cell therapy product within 12 months prior to randomization; any prior exposure to CAP-1002 will be excluded.
• Treatment with an investigational product within 6 months prior to randomization.
• History, or current use, of drugs or alcohol that could impair the ability to comply with participation in the trial.
• Inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator.
• Inability to undergo a cardiac MRI. For Cohort B Only - Subjects with a known hypersensitivity to gadolinium may forgo the LGE assessment but must complete a cardiac MRI without contrast. For Cohort B Only - Subjects who are unable to tolerate gadolinium due to renal insufficiency as measured by an estimated Glomerular Filtration Rate (eGFR) less than 60 mL/min/1.73 m2 may forgo the LGE assessment but must complete a cardiac MRI without contrast.
• For Cohort B: Subjects with PUL entry score 6, Exon 44 skipping amenable, or Exon 3 through 7 deletions are excluded from participation.
BIOLOGICAL: CAP-1002, BIOLOGICAL: Placebo
Muscular Dystrophies, Muscular Dystrophy, Duchenne, Muscular Disorders, Atrophic, Muscular Diseases, Neuromuscular Diseases, Genetic Diseases, X-Linked, Genetic Diseases, Inborn, Nervous System Diseases
Duchenne Muscular Dystrophy, Cell Therapy, Performance of the Upper Limb, Ambulatory, Non-Ambulatory
Children’s Health
Pediatric Radiation Oncology With Movie Induced Sedation Effect (PROMISE)
PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect) is an interactive incentive-based movie system that integrates with a video surveillance gating module (VisionRT) as an alternative sedation solution for pediatric patients undergoing radiation treatment (RT). This single-arm, open label, single-center phase II clinical trial is to implement PROMISE for all children ages 3-11 who are planned to undergo RT at the institution. The primary goal is to decrease the total number of pediatric patients who require general anesthesia through the use of PROMISE, with secondary goals being to assess the impact that PROMISE has on patient/family anxiety and quality of life, treatment time and clinical efficiency, and overall cost. The investigators hypothesize that PROMISE will lead to a reduction in the percentage of patients ages 3-7 who require general anesthesia use from 70% (historical control) to 30%.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kiran Kumar
ALL
3 Years to 11 Years old
PHASE2
NCT05148078
STU-2021-1005
Inclusion Criteria:
• Planned to undergo radiation treatment
• Age 3-11 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Parents or guardians with the ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Subjects with documented medical behavior conditions or other conditions necessitating anesthesia use
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects whose parents opt to not include them (the subject) in the clinical trial.
OTHER: PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect)
Pediatric Cancer, Bones and Joints, Brain and Nervous System, Eye and Orbit, Kidney, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Lymphoid Leukemia, Multiple Myeloma, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Rectum, Soft Tissue, Thyroid
radiotherapy
UT Southwestern; Children’s Health
Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL (IDEAL2)
This study is for older children, adolescents, and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL). Higher amounts of body fat is associated with resistance to chemotherapy in patients with B-ALL. Chemotherapy during the first month causes large gains in body fat in most people, even those who start chemotherapy at a healthy weight. This study is being done to find out if caloric restriction achieved by a personalized nutritional menu and exercise plan during routine chemotherapy can make the patient's ALL more sensitive to chemotherapy and also reduce the amount of body fat gained during treatment. The goals of this study are to help make chemotherapy more effective in treating the patient's leukemia as demonstrated by fewer patients with leukemia minimal residual disease (MRD) while also trying to reduce the amount of body fat that chemotherapy causes the patient to gain in the first month.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
All
10 Years to 25 Years old
Phase 2
NCT05082519
STU-2022-0479
Inclusion Criteria:
• Patients must be ≥ 10.0 and <26.0 years of age.
• Patients must have a diagnosis of de novo B-ALL
• Patients must have a M3 marrow (>25% blasts by morphology) or at least 1,000/µL circulating leukemia cells in PB confirmed by Flow Cytometry (or other convincing evidence of a B-ALL diagnosis not meeting above criteria following central review by the Study Hematopathologist and Study Chair or Vice-Chair).
• The treatment regimen must be the first treatment attempt for B-ALL-
• Must be a multi-agent induction regimen inclusive of vincristine, glucocorticoid, pegaspargase/calaspargase, and daunorubicin or doxorubicin and with a planned duration <35 days.
• Organ function must meet that required for initiation of chemotherapy
• Patients at diagnosis must meet Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age (or be expected to recover prior to Day 8) .
• If the patient is a female of childbearing potential, a negative urine or serum pregnancy test is required within two weeks prior to enrollment.
Exclusion Criteria:
• Patient will be excluded if they are underweight at time of enrollment (BMI% <5th percentile for age for patients age 10-19 years, BMI <18.5 in patients 20-29 years).
• Patients with Down syndrome or a DNA fragility syndrome (such as Fanconi anemia, Bloom syndrome) will be excluded.
• Patient receiving a SJCRH-style "Total Therapy" regimen will be excluded.
• Patients receiving anti-CD20 monoclonal antibody therapy during induction therapy.
• Patients will be excluded if they received treatment for a previous malignancy.
• Patient will be excluded if they are pregnant.
• Patient will be excluded if they have a pre-diagnosis requirement for enteral or parenteral supplementation .
• Patient will be excluded due to inability to perform the intervention (e.g., specific nutritional needs, severe developmental delay, paraplegia)
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
Behavioral: IDEAL2 Intervention
B-cell Acute Lymphoblastic Leukemia, Obesity, Lymphoid Leukemia
obesity, leukemia, B-cell leukemia, Pediatric obesity, Pediatric ALL
Children’s Health
Premedication for Less Invasive Surfactant Administration Study (PRELISA) (PRELISA)
The purpose of this study is to conduct a double blinded randomized control trial to determine the safety and efficacy of using IV fentanyl and atropine prior to Less Invasive Surfactant Administration (LISA) procedure in preterm infants with Respiratory Distress Syndrome compared to the local standard of care to perform this procedure without any premedication. Hypothesis: In infants greater than or equal to 29 weeks gestational age requiring the Less Invasive Surfactant Administration procedure, premedication with a combination of IV atropine and IV fentanyl will be associated with fewer combined bradycardia events, defined as heartrate less than 100 beats per minute for longer than 10 seconds, and hypoxemia events, defined as saturations less than or equal to 80% for longer than 30 seconds, during the procedure compared with placebo. Specific Aims: - To determine if infants receiving IV fentanyl and atropine prior to LISA will have a decrease in hypoxemia and bradycardia events during the procedure compared to infants receiving placebo - To determine if infants receiving premedication prior to Less Invasive Surfactant Administration will have higher procedure first attempt success rate compared with infants receiving placebo - To determine the effect of premedication on cerebral oxygenation compared to placebo during and for 12 hours after Less Invasive Surfactant Administration using cerebral Near Infrared Spectroscopy - To determine the effect of premedication prior to Less Invasive Surfactant Administration on the need for mechanical ventilation for 24 hours after the procedure
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kathryn.Mazioniene@UTSouthwestern.edu
Venkatakrishna Kakkilaya
All
0 Hours to 72 Hours old
Phase 4
NCT05065424
STU-2021-0380
Inclusion Criteria:
• Infants ≥29 weeks gestational age between 0-72 hours of life on CPAP for respiratory support who qualify for the LISA procedure as determined by the primary team using Parkland OPTISURF guidelines
Exclusion Criteria:
• Infants requiring intubation prior to surfactant therapy
• Infants with known severe congenital anomalies (including complex congenital heart disease, airway, and central nervous system anomalies)
• Infants born to mothers with known opioid addiction or in a methadone treatment program
Drug: IV Atropine and Fentanyl Premedication Arm, Drug: IV Normal Saline Placebo Arm
Respiratory Distress Syndrome, Newborn, Lung/Thoracic
Premedication for Less Invasive Surfactant Administration, Fentanyl and Atropine for Less Invasive Surfactant Administration, Cerebral Near Infrared Spectroscopy monitoring in neonates, Premedication for LISA, Fentanyl and Atropine for LISA, Cerebral NIRS monitoring in neonates
Parkland Health & Hospital System
TReatment for ImmUne Mediated PathopHysiology (TRIUMPH)
TReatment for ImmUne Mediated PathopHysiology (TRIUMPH) is a multi-center, three arm, randomized, controlled trial of immunosuppressive therapy for children with acute liver failure. The study will determine if suppressing inflammatory responses with either corticosteroids or equine anti-thymocyte globulin therapy improves survival for children with this rare, life-threatening condition.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Evelyn.Rojo@UTSouthwestern.edu
Norberto Rodriguez-Baez
ALL
1 Year to 18 Years old
PHASE2
NCT04862221
STU-2022-0154
Inclusion Criteria:
• Patient with liver injury of ≤ 6 weeks duration resulting in an international normalized ratio (INR) of ≥ 1.5 and \< 2.0 (not corrected by vitamin K) with evidence of hepatic encephalopathy (HE) or INR ≥ 2.0 without evidence of HE.
• Age is greater than or equal to 1 year and less than 18 years of age.
• Patient or their legally authorized representative(s) (LAR) must consent (and assent, if applicable) to be in the study and must have signed and dated an approved informed consent form which conforms to federal and institutional guidelines.
• Females of reproductive potential should not plan on conceiving children during the study and must agree to use a medically accepted form of contraception.
Exclusion Criteria:
• Evidence of active infection with Hepatitis A, B, C, E or evidence of acute herpes simplex virus (HSV) or adenovirus infection
• Travel within the past 3 months to an area highly endemic for Hepatitis E
• Diagnosis of hemophagocytic lymphohistiocytosis (HLH) Note: Patients with a history of consanguinity and/or central nervous system (CNS) dysfunction that is exaggerated compared to the degree of liver dysfunction (as judged by the site investigator) will not be enrolled until results of rapid genetic testing are available. Turn-around time for genetic testing results is estimated to be 72-96 hours.
• Aplastic anemia as defined by standardized criteria \[1\] diagnosed prior to enrollment
• Diagnosis of autoimmune Hepatitis (AIH)
• Diagnosis of acute Wilson disease
• Diagnosis of inborn error of metabolism Note: Suspicion of metabolic disease is not an exclusion for entry into the Trial.
• Diagnosis of acute drug or toxin-induced liver injury
• History of recreational drug use within the past 4 weeks
• Therapy with an immunosuppressive agent, including chemotherapy, biological therapies or an experimental drug or device within the past 6 weeks
• Liver injury due to ischemia
• Liver dysfunction diagnosed more than 6 weeks prior to screening
• History of allergy to horse dander
• Sepsis
• Imminent risk of death as judged by the clinical site investigator, including but not limited to; signs of cerebral herniation at the time of enrollment and presence of intractable arterial hypotension
• Solid organ or stem cell transplant recipient
• Pregnant or breast-feeding at the time of proposed study entry
• Clinical AIDS or HIV positive
• History of any form of malignant neoplasm and/or tumors treated within five years prior to study entry (other than non-melanoma skin cancer or in situ cervical cancer) or where there is current evidence of recurrent or metastatic disease
• Received a live-virus vaccine within 4 weeks of study entry
• Patients with positive respiratory secretion testing for respiratory viral infection including SARS-CoV-2, influenza and respiratory syncytial virus only if they also have declining respiratory function
• Psychiatric or addictive disorders that would preclude obtaining informed consent/assent
• Patient is unwilling or unable to adhere with study requirements and procedures
• Currently receiving other experimental therapies
DRUG: High-dose methylprednisolone, DRUG: Equine anti-thymocyte globulin, DRUG: Prednisolone, DRUG: Placebo for prednisolone, DRUG: Placebo for infusions, DRUG: Diphenhydramine, DRUG: Methylprednisolone
Acute Liver Failure, Fulminant Hepatic Failure, Hepatic Encephalopathy, Acute Liver Injury, Immune Dysregulation, Liver
hepatic insufficiency, liver diseases, liver failure, anti-thymocyte agents
Children’s Health
CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Months to 30 Years old
PHASE1
NCT04870944
STU-2023-0600
Inclusion Criteria:
* Parts A and B1: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* Part B2 (relapsed/refractory osteosarcoma): Patients must be \>= 12 months and =\< 30 years of age at the time of study enrollment
* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
* Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible
* Part B1: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27M-mutant diffuse midline gliomas previously treated with radiation therapy
* Part B2: Patients with relapsed or refractory osteosarcoma
* Part A: Patients must have either measurable or evaluable disease
* Part B1 and B2: Patients must have measurable disease
* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Easter 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 a Karnofsky or Lansky score \>= 50%
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy \[XRT\]/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to CBL0137
* For patients with solid tumors without known bone marrow involvement:
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* For patients with solid tumors without known bone marrow involvement:
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/gender as follows (performed within 7 days prior to enrollment unless otherwise indicated):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* Patients with solid tumors:
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with solid tumors:
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)
* Shortening fraction of \>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated)
* Ejection fraction of \>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)
* Corrected QT (QTC) \< 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)
* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are receiving drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy
* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy
* Patients with known peripheral vascular disease are excluded
* Patients with a history of pro-thrombotic disorder are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Echocardiography, DRUG: FACT Complex-targeting Curaxin CBL0137
Diffuse Midline Glioma, H3 K27M-Mutant, Metastatic Malignant Neoplasm in the Central Nervous System, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Osteosarcoma, Recurrent Primary Malignant Central Nervous System Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Osteosarcoma, Refractory Primary Malignant Central Nervous System Neoplasm, Bones and Joints, Brain and Nervous System, Lymphoma
Children’s Health
CHIlled Platelet Study "CHIPS" (CHIPS)
A phase 3 randomized partial blind storage duration ranging study in patients undergoing complex cardiac surgery that will compare the transfusion of cold stored platelets to standard room temperature stored platelets. The primary objective is to establish that cold stored platelets have a non-inferiority (or superiority) to room temperature platelets.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Erryn.Hopson@UTSouthwestern.edu
Philip Greilich
All
0 Days to 84 Years old
Phase 3
NCT04834414
STU-2021-0445
Inclusion Criteria:
• Viable neonates ≥ 3 kg at time of enrollment (as defined in Section 4.1) OR age greater than 28 days and less than 85 years of age at time of consent; AND
• Planned complex cardiac surgery with planned use of cardiopulmonary bypass, with an expectation of bleeding requiring platelet transfusion.
Exclusion Criteria:
• Expected order for washed or volume reduced platelets
• Patient with known anti-platelet antibodies
• Platelet transfusion refractoriness due to anti-HLA antibodies
• Known or suspected pregnancy
• Previously randomized in this study
• Conscious objection or unwillingness to receive blood products
• Known IgA deficiency
• Known congenital platelet disorder
• Known congenital bleeding disorder
• Planned post-operative extracorporeal membrane oxygenation (ECMO), ventricular assist device (VAD), and/or continuous renal replacement therapy (CRRT)/ hemodialysis
• Patients intended to receive whole blood either intra-operative or post-operative for bleeding
• Platelet transfusion (of any type) within 24 hours prior to the date of surgery
• Pre-operative thrombocytopenia, defined as platelet count <75x10(9)/L, based on the most recent labs completed within 72 hours prior to the date of surgery.
Biological: Cold Stored Platelets, Biological: Room Temperature Platelets
Acute Blood Loss, Cardiovascular
platelets, cold-stored platelets, bleeding, hemostasis, complex cardiac surgery
UT Southwestern; Children’s Health; Parkland Health & Hospital System
A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (FIREFLY-1)
FIREFLY-1 is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of oral pan-RAF inhibitor DAY101 in pediatric, adolescent, and young adult patients with recurrent or progressive low-grade glioma or an advanced solid tumor harboring a known BRAF alteration.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
All
6 Months to 25 Years old
Phase 2
NCT04775485
STU-2022-0878
Inclusion Criteria:
• Age 6 months to 25 years with:
• Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF alteration
• Arm 3: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion
• Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating BRAF alteration
• Must have received at least one line of systemic therapy and have evidence of radiographic progression
• Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1 (Arm 3) criteria
Exclusion Criteria:
• Patient's tumor has additional previously-known activating molecular alterations
• Patient has symptoms of clinical progression in the absence of radiographic progression
• Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)
• Other inclusion/exclusion criteria as stipulated by protocol may apply
Drug: DAY101
Low-grade Glioma, Advanced Solid Tumor, Brain and Nervous System
Children’s Health
A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling
This is a Phase 1/2, multicenter, open-label trial of avapritinib in participants 2 to < 18 years of age with advanced relapsed/refractory (R/R) solid tumors, including central nervous system (CNS) tumors, that harbor a PDGFRA and/or KIT mutation (including non-synonymous point mutations, insertions, and deletions) or amplification, or DMG-H3K27a who have no available curative treatment options. This is a single-arm trial in which all participants will receive avapritinib. The study consists of 2 parts: dose confirmation, safety, and PK (Part 1) and initial efficacy, safety, and PK at the Part 2 recommended dose (Part 2).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
All
2 Years to 17 Years old
Phase 1/Phase 2
NCT04773782
STU-2021-0904
Inclusion Criteria
• Participant must be 2 to < 18 years of age at the time of signing the informed consent.
• Diagnosis
• Participant has confirmed diagnosis of R/R solid tumor, including CNS tumors, with a mutation (including non-synonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available. Participant with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor. OR
• Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator.
• Participants with CNS disease should be on a stable (≤ 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent: a. Part 1: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants with DMG-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors that have progressed despite prior therapy, who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. For up to 5 Participants with newly diagnosed DMG-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (< 16 years of age) or Karnofsky (≥ 16 years of age) score of at least 50. If the Participant is unable to walk due to paralysis, but is mobile in a wheelchair, the participant is considered ambulatory for the purpose of assessing their performance status.
• Participant agrees to utilize contraception consistent with local regulations.
• Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential.
• Female participants: Agree to use effective contraception, as defined in Section
• 4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia.
• Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines. Exclusion Criteria
• Participant has any of the following within 14 days before the first dose of study treatment:
• Platelet count < 75 × 10^9/L (< 100 × 10^9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
• Absolute neutrophil count (ANC) < 1.0 × 10^9/L.
• Hemoglobin < 8.0 g/dL with no RBC transfusion ≤ 7 days prior to the measurement.
• AST or ALT > 3 × the ULN for age; except in Participants with tumor involvement of the liver who must not have AST and ALT > 5 × ULN for age.
• Total bilirubin > 1.5 × ULN for age; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
• Serum creatinine > 1.5 × ULN for age.
• International normalized ratio or prothrombin time (PT) > ULN (> 1.5 × ULN if on prophylactic reversible anticoagulants).
• Participant has a QTcF > 470 msec. Participant has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Participant has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (> 95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second-degree heart block or third-degree heart block).
• Participant received the following systemic antineoplastic therapies:
• Temozolomide within 4 weeks prior to the first dose of study drug
• Nitrosurea within 6 weeks prior to the first dose of study drug
• Any other systemic antineoplastic therapy (including experimental therapy) within 5 half-lives or 28 days prior to the first dose of study drug, whichever is shorter.
• Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or nontarget lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for Participants with CNS tumors). Craniospinal irradiation within 6 weeks prior to the first dose of avapritinib.
• All AEs related to other antineoplastic therapies (eg, systemic antineoplastics, radiotherapy) must have resolved to Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib.
• Participant has previously received treatment with avapritinib.
• Participant received autologous stem cell transplant following myeloablative therapy or chimeric antigen receptor T cell therapy within 3 months prior to the first dose of avapritinib or prior allogeneic stem cell transplant within 1 year and no evidence of Grade 1 or greater graft-versus-host disease and no immunosuppressants for graft-versus-host disease (steroids for primary malignancy being permitted). Participants who received stem cell reinfusion following nonmyeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1.
• Participant requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers.
• Participant has had a major surgical procedure within 14 days of the first dose of study treatment (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
• Participant has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• Female subjects of childbearing potential who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment.
• Participant is pregnant, as documented by a serum β-hCG pregnancy test consistent with pregnancy obtained at Screening and within 72 hours before the first dose of study treatment. Participants with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (premenarchal, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test.
• Participant is breastfeeding.
• Participant has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the Participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• History of thrombosis requiring treatment within the past 6 months. This exclusion does not apply to catheter-related thrombosis if the catheter has been removed and did not require any other treatment in the previous 3 months.
• Participants who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants.
• Participants who are unable to swallow tablets (in Part 1) or minitablets (in Part 2) within the sprinkle capsules.
• Participants with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are: Participants with primary CNS tumors (provided they have not had CNS bleeding within 2 weeks of the first dose of avapritinib) or Participants with punctate hemorrhages < 3 mm.
• History of a seizure disorder that is not well controlled on current antiepileptic medications.
• Participant is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions.
• Participant must be 2 to < 18 years of age at the time of signing the informed consent.
• Diagnosis
• Participant has confirmed diagnosis of R/R solid tumor, including CNS tumors, with a mutation (including non-synonymous point mutations, insertions, and deletions) in PDGFRA and/or KIT (confirmed by local mutational testing of tumor sample) that has progressed despite standard therapy and no alternative treatment option is available. Participant with R/R solid tumors with only PDGFRA and/or KIT amplifications may be included with approval from the Sponsor. OR
• Participant has confirmed diagnosis of DMG-H3K27a (confirmed by local testing of tumor sample) that has failed standard therapy or for which no standard therapy that may convey clinical benefit exists, as judged by the investigator.
• Participants with CNS disease should be on a stable (≤ 10% change) or decreasing dose of corticosteroids for at least 7 days prior to first dose of avapritinib, with no plans for dose escalation.
• Disease extent: a. Part 1: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) (for CNS tumors). If radiation therapy has been administered, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. b. Part 2: All participants must have at least 1 measurable lesion as defined by RECIST v1.1 or RANO (for CNS tumors). For Participants with DMG-H3K27a or PDGFRA and/or KIT mutant/amplified solid tumors, including CNS tumors that have progressed despite prior therapy, who have received radiation therapy, at least 1 measurable lesion must not have been irradiated, or must have clearly progressed since being irradiated as per RANO and must be ≥ 12 weeks from radiation to any target lesion. For up to 5 Participants with newly diagnosed DMG-H3K27a where there is no standard therapy that may convey clinical benefit exists as judged by the investigator, progression of disease of a measurable lesion after irradiation is not required.
• A Lansky (< 16 years of age) or Karnofsky (≥ 16 years of age) score of at least 50. If the Participant is unable to walk due to paralysis, but is mobile in a wheelchair, the participant is considered ambulatory for the purpose of assessing their performance status.
• Participant agrees to utilize contraception consistent with local regulations.
• Male participants: Are vasectomized, or agree to use condoms, as defined in Section 5.4.2, from the start of Screening until 6 weeks after the last dose of study treatment, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant, see Section 5.4.2), or have a female partner who is NOT of childbearing potential.
• Female participants: Agree to use effective contraception, as defined in Section
• 4.2, from the start of Screening until 6 weeks after the last dose of study treatment and have a male partner who uses a condom, or practice true abstinence (when this is in line with the preferred and usual lifestyle of the Participant), or have a male partner who is vasectomized with confirmed azoospermia.
• Participant can give written informed consent/assent before any study-specific Screening procedures (if feasible). Parental/legal guardian consent will be determined by local, regional, and/or national guidelines. Exclusion Criteria
• Participant has any of the following within 14 days before the first dose of study treatment:
• Platelet count < 75 × 10^9/L (< 100 × 10^9/L if a CNS tumor) with no platelet transfusion within 14 days prior to the measurement.
• Absolute neutrophil count (ANC) < 1.0 × 10^9/L.
• Hemoglobin < 8.0 g/dL with no RBC transfusion ≤ 7 days prior to the measurement.
• AST or ALT > 3 × the ULN for age; except in Participants with tumor involvement of the liver who must not have AST and ALT > 5 × ULN for age.
• Total bilirubin > 1.5 × ULN for age; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN.
• Serum creatinine > 1.5 × ULN for age.
• International normalized ratio or prothrombin time (PT) > ULN (> 1.5 × ULN if on prophylactic reversible anticoagulants).
• Participant has a QTcF > 470 msec. Participant has a familial or personal history of prolonged QT syndrome or Torsades de pointes.
• Participant has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension (> 95th percentile for age), or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (eg, Type II second-degree heart block or third-degree heart block).
• Participant received the following systemic antineoplastic therapies:
• Temozolomide within 4 weeks prior to the first dose of study drug
• Nitrosurea within 6 weeks prior to the first dose of study drug
• Any other systemic antineoplastic therapy (including experimental therapy) within 5 half-lives or 28 days prior to the first dose of study drug, whichever is shorter.
• Focal external beam radiotherapy, including stereotactic radiosurgery, within 6 weeks prior to the first dose of avapritinib to either target or nontarget lesions. Systemic radiopharmaceuticals, including nonstereotactic radiosurgery, within 2 weeks of the first dose of avapritinib (within 6 weeks for Participants with CNS tumors). Craniospinal irradiation within 6 weeks prior to the first dose of avapritinib.
• All AEs related to other antineoplastic therapies (eg, systemic antineoplastics, radiotherapy) must have resolved to Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy and/or ototoxicity) prior to the first dose of avapritinib.
• Participant has previously received treatment with avapritinib.
• Participant received autologous stem cell transplant following myeloablative therapy or chimeric antigen receptor T cell therapy within 3 months prior to the first dose of avapritinib or prior allogeneic stem cell transplant within 1 year and no evidence of Grade 1 or greater graft-versus-host disease and no immunosuppressants for graft-versus-host disease (steroids for primary malignancy being permitted). Participants who received stem cell reinfusion following nonmyeloablative therapy are eligible once they meet the peripheral blood count criteria in Exclusion Criterion #1.
• Participant requires ongoing treatment or has received treatment within 28 days before the start of avapritinib administration with drugs or foods that are strong CYP3A inhibitors or inducers.
• Participant has had a major surgical procedure within 14 days of the first dose of study treatment (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
• Participant has a history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of avapritinib. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.
• Female subjects of childbearing potential who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment. Male subjects who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of informed consent and for at least 6 weeks after the last dose of study treatment.
• Participant is pregnant, as documented by a serum β-hCG pregnancy test consistent with pregnancy obtained at Screening and within 72 hours before the first dose of study treatment. Participants with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor after pregnancy has been ruled out. Female subjects of nonchildbearing potential (premenarchal, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) do not require a serum β-hCG test.
• Participant is breastfeeding.
• Participant has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the Participant; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
• History of thrombosis requiring treatment within the past 6 months. This exclusion does not apply to catheter-related thrombosis if the catheter has been removed and did not require any other treatment in the previous 3 months.
• Participants who require anticoagulants, with the exception of stable doses of prophylactic reversible anticoagulants.
• Participants who are unable to swallow tablets (in Part 1) or minitablets (in Part 2) within the sprinkle capsules.
• Participants with a known risk of intracranial bleeding, such as a brain aneurysm that has not been removed or repaired, or a history of intracranial bleeding within the past year, or radiographic evidence of hemorrhage on Screening MRI. Exceptions are: Participants with primary CNS tumors (provided they have not had CNS bleeding within 2 weeks of the first dose of avapritinib) or Participants with punctate hemorrhages < 3 mm.
• History of a seizure disorder that is not well controlled on current antiepileptic medications.
• Participant is unwilling or unable to comply with scheduled visits, treatment administration plan, laboratory tests, or other study procedures and study restrictions.
Drug: avapritinib
Solid Tumor, Unspecified, Child, Relapsed Solid Neoplasm, CNS Tumor, Brain and Nervous System, Sarcoma
KIT, PDGFRA, Relapsed/Refractory Solid Tumor, Glioma, H3K27M, DMG-H3K27a
Children’s Health
VITAS: Atezolizumab in Combination with Chemotherapy for Pediatric Relapsed/refractory Solid Tumors
This trial is a multi-center, non-randomized, open-label Phase I/II study evaluating the feasibility and efficacy of vincristine, irinotecan, temozolomide, and atezolizumab in children with relapsed/refractory solid tumors.
Call 214-648-5005
studyfinder@utsouthwestern.edu, cris.molina@childrens.com
Matthew Campbell
ALL
6 Months to 30 Years old
PHASE1
NCT04796012
STU-2021-0606
Inclusion Criteria:
• Signed informed consent
• Relapsed or refractory solid tumor after at least one prior course of therapy.
• Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
• Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met. * No metastatic or primary disease affecting the brainstem, midbrain, pons, or cerebellum, or within 10 mm of optic nerve * No history of leptomeningeal disease * No history of intracranial or spinal cord hemorrhage * No evidence of progression of neurologic deficit, in the investigator's judgment, within 7 days prior to initiation of study medications.
• Must have histologically confirmed rhabdomyosarcoma (RMS) for RMS efficacy cohort.
• Age ≥ 6 months and ≤ 30 years
• Lansky Performance Status (patients \< 16 years old) or Karnofsky Performance Status (patients ≥ 16 years old) ≥ 50
• Ability to comply with the study protocol, in the investigator's judgment
• For RMS efficacy cohort, disease must be measurable as defined by RECIST v1.1.
• For the feasibility cohort, disease must be evaluable, but patients enrolled in the feasibility cohort will be prospectively assessed for measurable disease, RMS patients will also be included in the RMS efficacy cohort.
• Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
• Availability of a tumor specimen suitable for determination of PD-L1 status, either from initial diagnosis or from a recurrence.
• For PD-L1 staining to be performed at the central site, a formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report prior to study enrollment.
• Patients for whom the required number of slides are not available may still be eligible to enroll on study with PI approval
• For the RMS efficacy cohort, it will be required that at least 8 of 17 patients have PD-L1(+) tumor. PD-L1 status will be determined at time of enrollment for all patients. When the maximum allowable number of PD-L1(-) patients has been enrolled and treated on study, PD-L1 positivity will be required for all further enrolled patients.
• Staining will be performed in the central site CAP/CLIA-certified laboratory using the 22c3 antibody for immunohistochemical analysis
• PD-L1(+) status will be defined as staining on ≥1% of tumor cells or ≥1% of stroma.
• For the feasibility cohort, PD-L1 positivity is not required but will be performed centrally in all cases for exploratory biomarker studies.
• Adequate organ and marrow function as defined by the following laboratory values obtained within 21 days prior to initiation of study medication.
• For patients without known bone marrow involvement: * Absolute neutrophil count ≥ 1.0 x 10\^9 / L (1000/µL) without granulocyte colony-stimulating factor support (≥14 days after the last dose of a long-acting growth factor such as pegfilgrastim, or 7 days after short-acting growth factor) * Absolute lymphocyte count ≥ 0.5 x 10\^9 / L (500/µL) * Platelet count ≥ 75 x 10\^9 / L (75,000/µL) without transfusion in the last 7 days
• Patients with known bone marrow metastatic disease will be eligible for the study if they meet the following criteria: * Patients with documented liver metastases: AST and ALT ≤ 5 x ULN * Patients with documented liver or bone metastases: ALP ≤ 5 x ULN * Absolute neutrophil count (ANC) ≥ 750/mm\^3 * Absolute lymphocyte count ≥ 0.4 x 10\^9 / L (400/µL) * Platelet count ≥ 50,000/mm\^3 (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions) * These patients will not be evaluable for hematologic toxicity. At least 4 of 6 patients in the feasibility cohort must be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.
• Total bilirubin ≤1.5 x upper limit of normal (ULN) for age (Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN)
• AST (SGOT) and ALT (SPGT) ≤ 2.5 x ULN for age
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• Creatinine ≤ 1.5 x ULN for age or creatinine clearance (or radioisotope glomerular filtration rate) ≥ 70 mL/min/1.73 m2
• Left ventricular ejection fraction ≥ 50% or shortening fraction ≥ 30%
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Patients may be transfused to meet this criterion.
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV and hepatitis B surface antigen (HBsAg) tests at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, vincristine, and temozolomide. Women must refrain from donating eggs during this same period.
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus), regardless of sexual orientation or marital status.
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
• With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, irinotecan, and temozolomide. Men must refrain from donating sperm during this same period.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria:
• Pregnancy or breast-feeding:
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
• Medical conditions that are excluded:
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Guillain-Barré syndrome, multiple sclerosis, or Kawasaki syndrome with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met at study initiation: (1) Rash must cover less 10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled tumor-related pain * Patients requiring pain medication must be on a stable regimen at study entry for at least 2 weeks. Intermittent use of as-needed medication is allowed during this period.
• Clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (at the discretion of the treating physician)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of severe asthma or uncontrolled asthma
• Dyspnea at rest or requirement for supplemental oxygen
• Uncontrolled seizures. Patients taking a stable dose of anticonvulsants (for 2 weeks) are permitted, as long as they are not strong inducers or inhibitors of CYP3A4.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications in the opinion of the treating investigator
• Washout periods from prior therapies:
• Myelosuppressive chemotherapy or radiotherapy within 21 days prior to starting study treatment. * Subjects must have recovered from all acute prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism).
• Non-myelosuppressive cancer therapy, such as kinase inhibitors, within 7 days prior to study treatment.
• Treatment with monoclonal antibodies with long half-lives, within 3 half-lives prior to study treatment.
• Treatment with targeted cellular therapies within 28 days prior to starting study treatment.
• Major surgical procedure, other than for diagnosis, within 30 days prior to initiation of study treatment, or anticipation of the need for a major surgical procedure during the first four cycles of the study. * Biopsy tissue collection or placement of a vascular access device is permitted if the site has healed prior to initiation of study medications. * For patients with CNS disease, no neurosurgical resection, brain biopsy, or stereotactic/whole-brain radiation within 30 days prior to Cycle 1, Day 1
• Treatment with a live, attenuated vaccine within 30 days prior to initiation of study treatment, or anticipation of the need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• Treatment with investigational therapy within 21 days prior to initiation of study treatment or concurrent participation with another investigational agent
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with the following exceptions: * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained. * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. * Patients with CNS disease can be receiving concurrent treatment with corticosteroids with approval from the Principal Investigator. Patients must be receiving a stable or decreasing dose for ≥ 5 days prior to the baseline MRI scan and at the time of drug initiation. The Principal Investigator should be informed when steroid doses are increased because of declining patient status.
• Use of strong CYP3A4 inhibitors or inducers or strong UGT1A1 inhibitors within 12 days of Cycle 1, Day 1.
• Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
• Treatment with herbal cancer therapy within 1 week prior to initiation of study medications.
• Treatment with a long-acting hematopoietic growth factor (such as pegfilgrastim) within 2 weeks prior to initiation of study medications, or a short-acting hematopoietic growth factor (such as G-CSF) within 1 week prior to initiation of study medications.
• Prior treatments:
• Prior allogeneic stem cell or solid organ transplantation
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies to include all anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Subjects must not have previously progressed while receiving regimens that include irinotecan or temozolomide. Patients who have received irinotecan or temozolomide and did not progress while on these medications are eligible.
• Known ongoing or untreated infection, including, but not limited to bacteremia, active tuberculosis, or severe pneumonia
• Active tuberculosis
• Current treatment with anti-viral therapy for HBV
• Active hepatitis C
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Known allergy or hypersensitivity to any component of the study medications
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
DRUG: Atezolizumab, DRUG: Vincristine, DRUG: Irinotecan, DRUG: Temozolomide
Solid Tumor, Rhabdomyosarcoma, Brain and Nervous System, Colon, Lymphoma, Soft Tissue
Relapsed solid tumor, Refractory solid tumor, Rhabdomyosarcoma
UT Southwestern; Children’s Health
Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma
This phase III trial compares the effects of nivolumab with chemo-immunotherapy versus chemo-immunotherapy alone in treating patients with newly diagnosed primary mediastinal B-cell lymphoma (PMBCL). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab. Chemotherapy 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. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nivolumab with chemo-immunotherapy may help treat patients with PMBCL.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
2 Years and over
PHASE3
NCT04759586
STU-2021-0574
Inclusion Criteria:
* Age \>= 2 years
* Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma
* Children's Oncology Group (COG) Institutions: Use Karnofsky for patients \>= 17 and \< 18 years of age and Lansky for patients \< 17 years of age
* Adults (age 18 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 actual body weight
* Pediatric Patients (age \< 18 years): The following must have been obtained within 14 days prior to registration:
* Measured or calculated (based on institutional standard) creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2, or
* Serum creatinine =\< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/gender as follows:
* Age : 2 to \< 6 year; 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 to \< 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
* Patients with abnormal liver function will be eligible to enroll if the lab abnormality is thought to be due to the lymphoma or Gilbert's syndrome
* Age \>= 18 years: Ejection fraction of \>= 50% by echocardiogram
* Age \< 18 years: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* 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:
* Administration of prior anti-cancer therapy except as outlined below:
* A short course (=\< 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms
* A single course of COP (cyclophosphamide, vincristine, and prednisone)
* One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131), or intrathecal chemotherapy that has not started more than 21 days prior to enrollment
* Active ischemic heart disease or heart failure
* Active uncontrolled infection
* Central nervous system (CNS) involvement of lymphoma
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this trial
* Active autoimmune disease that has required systemic treatment (such as disease modifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years. Replacement therapy such as thyroxine, insulin or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment
* In patients \< 18 years of age hepatitis B serologies consistent with past or current infections
* Patients with severe hepatic impairment (Child-Pugh class C or serum total bilirubin \> 5.0 mg/dL) unless thought to be due to lymphoma or Gilbert's syndrome
* 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
* Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of \< 1% per year when used consistently and correctly) for the duration of their study participation
* Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last dose of rituximab PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography, DRUG: Etoposide Phosphate, BIOLOGICAL: Filgrastim, PROCEDURE: Lumbar Puncture, BIOLOGICAL: Nivolumab, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Positron Emission Tomography, DRUG: Prednisolone, DRUG: Prednisone, RADIATION: Radiation Therapy, BIOLOGICAL: Rituximab, BIOLOGICAL: Rituximab and Hyaluronidase Human, DRUG: Vincristine Sulfate
Primary Mediastinal Large B-cell Lymphoma, Lymphoma
Children’s Health
Ferric Citrate and Chronic Kidney Disease in Children (FIT4KID)
We will conduct a 12-month, double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23, primary endpoint) in 160 pediatric patients (80 in each of the two arms) aged 6-18 years of either sex with chronic kidney disease (CKD) stages 3-4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) FC or 2) FC placebo. Participants will be recruited from 20 core clinical sites.
Call 214-648-5005
studyfinder@utsouthwestern.edu, melaku.lemma@childrens.com
Raymond Quigley
ALL
6 Years to 18 Years old
PHASE2
NCT04741646
STU-2020-1055
Inclusion Criteria:
• Ages 6 to 18 years (inclusive);
• Estimated Glomerular Filtration Rate (GFR) of 15-59 ml/min per 1.73 m2 by modified Chronic Kidney disease in Children (CKiD) formula;56
• Serum phosphate within age appropriate normal levels;
• Serum ferritin \<500 ng/ml and TSAT \<50%;
• For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or erythropoiesis-stimulating agents (ESAs) such treatments must have stable dosing for at least 2 weeks prior to screening;
• Able to swallow tablets;
• Able to eat at least two meals a day;
• In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.
Exclusion Criteria:
• Patients currently treated with phosphate binders.
• History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo)
• Current intestinal malabsorption, documented in the medical record; significant GI disorders including GI bleeding or active inflammatory bowel disease, inflammatory bowel syndrome, and/or Crohn's Disease
• Anticipated initiation of dialysis or kidney transplantation within 6 months
• Current or planned future systemic immunosuppressive therapy
• Prior solid organ transplantation
• Receipt of bone marrow transplant within two years of screening
• Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol
• Patients participating in other interventional study (observational study participation permitted)
• Poor adherence to medical treatments in the opinion of the investigator
• Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome
• Cystinosis
• Fanconi syndrome
DRUG: Ferric Citrate, DRUG: Placebo
Chronic Kidney Diseases, Kidney
Pediatric, CKD, Phosphate Binder
Children’s Health