[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06465199":3,"trial-entities:NCT06465199":316,"trial-summary:NCT06465199":320},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":26,"study_type":28,"primary_purpose":29,"phases":30,"enrollment_info":33,"interventions":36,"primary_outcomes":52,"secondary_outcomes":64,"sex":82,"minimum_age":17,"maximum_age":83,"healthy_volunteers":84,"eligibility_criteria":85,"std_ages":101,"locations":104,"central_contacts":301,"overall_officials":306,"references":311,"see_also_links":312},"NCT06465199","BCC020","Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas","A Phase I\u002FII Study Using Eflornithine (DFMO) and AMXT 1501 for Relapsed and Refractory Neuroblastoma, CNS Tumors, and Sarcomas","RECRUITING","2035-05","2026-08","2026-08-12","2026-05-13","Milton S. Hershey Medical Center","OTHER",true,"The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is one that has not been approved by the U.S. Food \\& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.\n\nThe goals of this part of the study are:\n\n* Establish a recommended dose of AMXT 1501 in combination with DFMO\n* Test the safety and tolerability of AMXT 1501 in combination with DFMO\n* To determine the activity of study treatments chosen based on:\n* How each subject responds to the study treatment\n* How long a subject lives without their disease returning\u002Fprogressing",null,[19,20,21,22,23,24,25],"Atypical Teratoid\u002FRhabdoid Tumor","Embryonal Tumor With Multilayered Rosettes","Ewing Sarcoma","Diffuse Intrinsic Pontine Glioma","Osteosarcoma","Neuroblastoma","DIPG Brain Tumor",[27],"DFMO","INTERVENTIONAL","TREATMENT",[31,32],"PHASE1","PHASE2",{"count":34,"type":35},289,"ESTIMATED",[37,48],{"type":38,"name":39,"description":40,"armGroupLabels":41,"otherNames":46},"DRUG","Eflornithine (DFMO)","Oral DFMO capsules",[42,43,44,45],"Phase I","Phase II- Arm A: AMXT 1501 + DFMO","Phase II- Arm B: DFMO Alone","Safety Run-in",[47],"Difluoromethylornithine",{"type":38,"name":49,"description":50,"armGroupLabels":51},"AMXT 1501 Dicaprate","Capsule",[42,43,45],[53,57,61],{"measure":54,"description":55,"timeFrame":56},"Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability","To evaluate the safety, tolerability and recommended phase 2 dose (RP2D) of AMXT 1501 in combination with oral DFMO in pediatric and young adult participants.","28 days",{"measure":58,"description":59,"timeFrame":60},"Phase II- Number of Cohort 1 participants with progression free survival (PFS) during study","To evaluate, in a prospective randomized clinical trial, the efficacy of eflornithine (DFMO) in combination with AMXT 1501 compared to DFMO alone in neuroblastoma (Cohort 1) based upon Progression Free Survival (PFS)","2 years plus 5 years follow up",{"measure":62,"description":63,"timeFrame":60},"Phase II- Number of Cohort 2-4 participants with progression free survival (PFS) during study","To evaluate the efficacy of eflornithine (DFMO) in combination with AMXT 1501 in non-randomized (Cohorts 2-4) based upon Progression Free Survival (PFS):\n\n2\\. Cohort 2-Relapsed\u002Frefractory Embryonal Tumor with Multilayered Rosettes (ETMR) Atypical Teratoid Rhabdoid Tumor (ATRT) 3. Cohort 3-Diffuse Intrinsic Pontine Glioma (DIPG) at diagnosis after standard of care radiation therapy 4. Cohort 4- Relapsed\u002Frefractory Ewing Sarcoma (EWS) and Osteosarcoma (OST)",[65,68,72,75,78],{"measure":66,"description":67,"timeFrame":60},"Phase I- Number of participants with progression free survival (PFS) during study","To evaluate the activity of AMXT 1501 in combination with DFMO based on Progression free survival (PFS)",{"measure":69,"description":70,"timeFrame":71},"Phase I- Determine the Overall Response Rate (ORR) of Participants using INSS Response","To evaluate the activity of AMXT 1501 in combination with DFMO based on Overall response rate (ORR)","2 years",{"measure":73,"description":74,"timeFrame":71},"Phase II- Determine the Overall Response Rate (ORR) of Participants using INSS Response","To evaluate the efficacy of eflornithine (DFMO) in combination with AMXT 1501 (Cohort 2-4) and in a randomized arm compared to DFMO alone in neuroblastoma (Cohort 1), based upon overall response rate (ORR).",{"measure":76,"description":77,"timeFrame":60},"Phase II- Length of time that participants experience Overall Survival (OS)","To evaluate the efficacy of eflornithine (DFMO) in combination with AMXT 1501 (Cohort 2-4) and in a randomized arm compared to DFMO alone in neuroblastoma (Cohort 1), based upon overall Survival (OS).",{"measure":79,"description":80,"timeFrame":81},"Phase II-Number of Participants with Adverse Events as a Measure of Safety and Tolerability","To evaluate the safety and tolerability profile of eflornithine (DFMO) in combination with AMXT 1501 in pediatric and young adult participants.","2 years plus 30 days","ALL","26 Years",false,{"inclusion":86,"exclusion":99,"raw_text":100},[87,88,89,90,91,92,93,94,95,96,97,98],"Relapsed\u002Frefractory Neuroblastoma (NB)","Relapsed\u002Frefractory Embryonal tumor with multilayer rosettes (ETMR)","Relapsed\u002Frefractory Atypical teratoid rhabdoid tumor (ATRT)","Newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)- radiologic diagnosis acceptable","Relapsed\u002Frefractory Ewing Sarcoma (EWS)","Relapsed\u002Frefractory Osteosarcoma (OST) 3. Tumor assessment:","Received at least one recent treatment for their relapse\u002Frefractory disease and is stable (SD) or better on this treatment.","Participants must not have disease in any organs (including lungs, liver, or brain).","Hematological: Hematological recovery as defined by ANC ≥750\u002FμL (unsupported- \\>24 hrs off G-CSF and 7 days off neulasta)","Liver: Adequate liver function as defined by AST and ALT \\\u003C10x upper limit of normal","Cardiac: all participants must have:","Renal: Participants must have adequate renal function defined as:",[],"Inclusion Criteria:\n\n1. Age:\n\n   All participants : Must be a maximum of 26 years of age at diagnosis\n\n   Age at enrollment by Phase:\n   1. Safety Run-in (Dose level 1)-The first three (3) participants enrolled will be ≥ 12 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the next three (3) participants enrolled who will be ≥6 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the Phase I.\n   2. Phase I and II: ≤ 26 years of age at diagnosis.\n2. Pathology\n\n   All participants must have a confirmed pathologic diagnosis of tumor type (except for DIPG):\n   * Relapsed\u002Frefractory Neuroblastoma (NB)\n   * Relapsed\u002Frefractory Embryonal tumor with multilayer rosettes (ETMR)\n   * Relapsed\u002Frefractory Atypical teratoid rhabdoid tumor (ATRT)\n   * Newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)- radiologic diagnosis acceptable\n   * Relapsed\u002Frefractory Ewing Sarcoma (EWS)\n   * Relapsed\u002Frefractory Osteosarcoma (OST)\n3. Tumor assessment:\n\n   Disease staging must be performed at baseline during the 28 day screening period prior to first dose of study drug.\n4. Disease Status:\n\n   Relapsed or Refractory Neuroblastoma Relapsed disease defined as: High-risk neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation, surgery, and immunotherapy, or according to a standard high-risk treatment\u002Fneuroblastoma protocol).\n\n   Refractory disease defined as: High-risk neuroblastoma that 1) failed to achieve CR after at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment\u002Fneuroblastoma protocol, or 2) progression during upfront therapy or 3) with disease remaining after standard immunotherapy.\n\n   Eligible NB participants may have active disease or no active disease.\n\n   NB participants with no active disease need to meet the following criteria:\n\n   Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.\n\n   NB participants with active disease need to meet the following criteria:\n   * Received at least one recent treatment for their relapse\u002Frefractory disease and is stable (SD) or better on this treatment.\n   * Participants must not have disease in any organs (including lungs, liver, or brain).\n\n   Relapsed or refractory ETMR\u002FATRT Participants that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive\u002Fprogressive to accepted curative therapy, including up-front chemotherapy and radiation and\u002For high-dose chemotherapy with stem cell rescue.\n\n   ETMR\u002FATRT participants with no active disease need to meet the following criteria:\n\n   Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.\n\n   ETMR\u002FATRT participants with active disease need to meet the following criteria:\n\n   • Received at least one recent treatment for their relapse\u002Frefractory disease and is stable (SD) or better on this treatment.\n\n   Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) Participants with DIPG to start greater than 30 days, and no longer than 60 days, after standard of care radiation therapy.\n\n   Participants with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of the pons on at least 1 axial T2-weighted image, are eligible. No histologic confirmation is required. Participants with metastatic disease are not eligible. Participants with a biopsy and no evidence of H3K27m mutations are eligible as long as they meet radiographic criteria. Participants with H3K27m altered DMG outside of the brainstem are not eligible. Participants with progression or recurrence after initial standard of care radiation are ineligible.\n\n   Relapsed or refractory Ewing sarcoma and osteosarcoma Participants that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for Ewing sarcoma and osteosarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy.\n\n   EWS\u002FOST Participants with no active disease need to meet the following criteria:\n\n   Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.\n\n   EWS\u002FOST Participants with active disease need to meet the following criteria:\n\n   • Received at least one recent treatment for their relapse\u002Frefractory disease and is stable (SD) or better on this treatment.\n5. Participants must be able to swallow capsules.\n6. Participants with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week and must not have progressive hydrocephalus at enrollment.\n7. Participants must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:\n\n   1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).\n   2. Small Molecule Inhibitor (anti-neoplastic agent): At least 7 days since the completion of therapy with a small molecule inhibitor. 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. The duration of this interval must be discussed with the Study Chair.\n   3. Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells except for anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.) which should be at least 2 weeks since prior treatment with a monoclonal antibody.\n   4. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.\n\n      Note: Participants with DIPG will be required to have had up front standard of care radiation. As above, participants with DIPG must be between 30-60 days post initial up- front radiation therapy.\n   5. Stem Cell Transplant:\n\n      1. Allogeneic: No evidence of active graft vs. host disease\n      2. Allo\u002FAuto: ≥ 45 days must have elapsed since transplant.\n   6. MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.\n8. Participants must have a Lansky or Karnofsky Performance Scale score of \\>\u002F= 60\n9. Participants must have adequate organ function at the time of enrollment:\n\n   * Hematological: Hematological recovery as defined by ANC ≥750\u002FμL (unsupported- \\>24 hrs off G-CSF and 7 days off neulasta)\n   * Liver: Adequate liver function as defined by AST and ALT \\\u003C10x upper limit of normal\n   * Cardiac: all participants must have:\n\n     1. Normal serum Cardiac Troponin Concentration\n     2. Normal BNP (B-type natriuretic peptide) Level\n     3. A QTcF ≤ 470 msec (or EKG with no significant findings)\n     4. Normal ECHO defined as:\n\n     i. Shortening fraction of ≥ 27% by echocardiogram, or ii. Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram\n   * Renal: Participants must have adequate renal function defined as:\n\n     1. For participants \\\u003C 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Bedside Schwartz equation is: \\[(0.413) X (Height in cm)\\] \u002F SCr\n     2. For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Cockcroft and Gault formula is: \\[(140-age) x (Wt in kg) x (0.85 if female)\\] \u002F (72 x SCr)\n10. Participants of childbearing potential must have a negative pregnancy test. Participants of childbearing potential must agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding.\n11. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).\n\nExclusion Criteria:\n\n1. BSA of \\\u003C0.25 m2\n2. Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.\n3. Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.\n4. Infection: Participants who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.\n5. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.",[102,103],"CHILD","ADULT",[105,122,136,150,164,177,190,203,217,231,245,259,273,287],{"facility":106,"status":8,"city":107,"state":108,"zip":109,"country":110,"contacts":111,"geoPoint":119},"University of Alabama\u002FChildren's of Alabama","Birmingham","Alabama","35233","United States",[112,116],{"name":113,"role":114,"email":115},"Bridget Tate","CONTACT","btate@peds.uab.edu",{"name":117,"role":118},"Elizabeth Alva","PRINCIPAL_INVESTIGATOR",{"lat":120,"lon":121},33.52066,-86.80249,{"facility":123,"status":8,"city":124,"state":125,"zip":126,"country":110,"contacts":127,"geoPoint":133},"Arkansas Children's Hospital","Little Rock","Arkansas","72202",[128,131],{"name":129,"role":114,"email":130},"Susan Hall","hallsf@archildrens.org",{"name":132,"role":118},"Kevin Bielamowicz",{"lat":134,"lon":135},34.74648,-92.28959,{"facility":137,"status":8,"city":138,"state":139,"zip":140,"country":110,"contacts":141,"geoPoint":147},"Connecticut Children's Hospital","Hartford","Connecticut","06106",[142,145],{"name":143,"role":114,"email":144},"Adam Barselau","abarselau@connecticutchildrens.org",{"name":146,"role":118},"Michael Isakoff",{"lat":148,"lon":149},41.76371,-72.68509,{"facility":151,"status":8,"city":152,"state":153,"zip":154,"country":110,"contacts":155,"geoPoint":161},"University of Florida","Gainesville","Florida","32611",[156,159],{"name":157,"role":114,"email":158},"Ashley Bayne","abayne@UFL.EDU",{"name":160,"role":118},"Joanne Lagmay",{"lat":162,"lon":163},29.65163,-82.32483,{"facility":165,"status":8,"city":166,"state":153,"zip":167,"country":110,"contacts":168,"geoPoint":174},"Nicklaus Children's Hospital","Miami","33155",[169,172],{"name":170,"role":114,"email":171},"Aixa Guadarrama","Aixa.Guadarrama@Nicklaushealth.org",{"name":173,"role":118},"Guillermo De Angulo",{"lat":175,"lon":176},25.77427,-80.19366,{"facility":178,"status":8,"city":179,"state":153,"zip":180,"country":110,"contacts":181,"geoPoint":187},"Arnold Palmer Hospital for Children","Orlando","32806",[182,185],{"name":183,"role":114,"email":184},"Marie Frankos","marie.frankos@orlandohealth.com",{"name":186,"role":118},"Jamie Libes-Bander",{"lat":188,"lon":189},28.53834,-81.37924,{"facility":191,"status":8,"city":192,"state":153,"zip":193,"country":110,"contacts":194,"geoPoint":200},"St. Joseph's Children's Hospital","Tampa","33614",[195,198],{"name":196,"role":114,"email":197},"Jennifer Manns","jennifer.manns@baycare.org",{"name":199,"role":118},"Don Eslin",{"lat":201,"lon":202},27.94752,-82.45843,{"facility":204,"status":8,"city":205,"state":206,"zip":207,"country":110,"contacts":208,"geoPoint":214},"Kapiolani Medical Center for Women and Children","Honolulu","Hawaii","96813",[209,212],{"name":210,"role":114,"email":211},"Andrea Siu","andrea.siu@kapiolani.org",{"name":213,"role":118},"Kelley Hutchins",{"lat":215,"lon":216},21.30694,-157.85833,{"facility":218,"status":8,"city":219,"state":220,"zip":221,"country":110,"contacts":222,"geoPoint":228},"Children's Mercy Hospitals and Clinics","Kansas City","Kansas","64108",[223,226],{"name":224,"role":114,"email":225},"Nicole Harvey","ndharvey@cmh.edu",{"name":227,"role":118},"Kevin Ginn",{"lat":229,"lon":230},39.11417,-94.62746,{"facility":232,"status":8,"city":233,"state":234,"zip":235,"country":110,"contacts":236,"geoPoint":242},"Cardinal Glennon Children's Medical Center","St Louis","Missouri","63104",[237,240],{"name":238,"role":114,"email":239},"Gina Martin","gina.martin@health.slu.edu",{"name":241,"role":118},"William Ferguson",{"lat":243,"lon":244},38.62727,-90.19789,{"facility":246,"status":8,"city":247,"state":248,"zip":249,"country":110,"contacts":250,"geoPoint":256},"Hackensack University Medical Center","Hackensack","New Jersey","07601",[251,254],{"name":252,"role":114,"email":253},"Kellie Florance","kellie.florance@hmhn.org",{"name":255,"role":118},"Derek Hanson",{"lat":257,"lon":258},40.88593,-74.04347,{"facility":260,"status":8,"city":261,"state":262,"zip":263,"country":110,"contacts":264,"geoPoint":270},"Penn State Milton S. Hershey Medical Center and Children's Hospital","Hershey","Pennsylvania","17033",[265,268],{"name":266,"role":114,"email":267},"Penn State Clinical Trials Group Email","ExtractClinicalTrials@pennstatehealth.psu.edu",{"name":269,"role":118},"Valerie Brown",{"lat":271,"lon":272},40.28592,-76.65025,{"facility":274,"status":8,"city":275,"state":276,"zip":277,"country":110,"contacts":278,"geoPoint":284},"Monroe Carrell Jr. Children's Hospital at Vanderbilt","Nashville","Tennessee","37232",[279,282],{"name":280,"role":114,"email":281},"Aida Constantinescu","aida.constantinescu@vumc.org",{"name":283,"role":118},"Daniel Benedetti",{"lat":285,"lon":286},36.16589,-86.78444,{"facility":288,"status":8,"city":289,"state":290,"zip":291,"country":110,"contacts":292,"geoPoint":298},"Children's Medical Center","Dallas","Texas","75235",[293,296],{"name":294,"role":114,"email":295},"Rachel Nam","rachel.nam@childrens.com",{"name":297,"role":118},"Tanya Watt",{"lat":299,"lon":300},32.78306,-96.80667,[302],{"name":303,"role":114,"phone":304,"email":305},"BCC Enroll","7175310003","BCCEnroll@pennstatehealth.psu.edu",[307],{"name":308,"affiliation":309,"role":310},"Giselle Saulnier Sholler, MD","Penn State Health Children's Hospital","STUDY_CHAIR",[],[313],{"label":314,"url":315},"Beat Childhood Cancer Research Consortium website","https:\u002F\u002Fresearch.beatcc.org\u002F",{"nct_id":4,"conditions":317,"biomarkers":319},[19,22,318,21,24,23],"Embryonal Tumor with Multilayered Rosettes",[],{"nct_id":4,"found":15,"summary":321,"prompt_version":331},{"design":322,"status":323,"heading":324,"summary":325,"follow_up":326,"word_count":327,"commitments":328,"compensation":329,"drugs_mentioned":330},"This is an interventional study with a planned enrollment of 289 participants. It will first establish a safe dose (Phase I) and then evaluate effectiveness (Phase II).","completed","Eflornithine (DFMO) and AMXT 1501 for Childhood Cancers","This study is testing two investigational oral drugs, eflornithine (DFMO) and AMXT 1501, in combination. These drugs are not yet approved by the FDA. The study aims to find the best dose of AMXT 1501 when given with DFMO, and to see how safe and effective this combination is for children and young adults up to 26 years old with certain cancers like Atypical Teratoid\u002FRhabdoid Tumor, Ewing Sarcoma, and Osteosarcoma. The researchers will look at how well participants respond to the treatment and how long they live without their disease getting worse (progression-free survival). This study is for patients up to 26 years old at diagnosis.","Participants in Phase II will be followed for progression-free survival for 2 years, with an additional 5 years of follow-up.",106,"Not specified in the trial record.","Not stated in the trial record.",[39],"v2"]