[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"relapsed-neuroblastoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:relapsed-neuroblastoma":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,9,0,[8,52,86,125,149,174,197,225,248],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":31,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":41,"startDateStruct":44,"completionDateStruct":46,"leadSponsor":48,"locationsCount":51},"100609221","phase-1-nkg2dzeta-nk-cell-conditioning-with-c7rgd2car-t-cells-for-patients-with-relapsed-or-refractory-osteosarcoma-or-neuroblastoma-100609221",false,"NCT07211737","NKG2D.Zeta-NK Cell Conditioning With C7R.GD2.CAR-T Cells for Patients With Relapsed or Refractory Osteosarcoma or Neuroblastoma","(INCITE-ON) Phase I Study of i15.NKG2D.Zeta-NK Cell Conditioning in the Tumor Micro-environment in Combination With C7R.GD2.CAR-T for the Treatment of Patients With Relapsed or Refractory Osteosarcoma or Neuroblastoma","PROCUREMENT INCLUSION:\n\n1. Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n\n   Or\n\n   Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n2. Karnofsky\u002FLansky score of 60% or greater.\n3. Informed consent and assent (as applicable) obtained from parent\u002Fguardian and child.\n4. Greater than 1 year of age.\n\nPROCUREMENT EXCLUSION:\n\n1. History of hypersensitivity to murine protein-containing products.\n2. Known presence of Human Anti-Mouse Antibodies (HAMA).\n3. Active autoimmune disease (requiring immunosuppressive treatment in the past 6 months).\n4. Primary brain tumor or known brain metastases (on evaluation by MIBG and\u002For PET if applicable, CT\u002FMRI\u002FLP not required).\n\nTREATMENT INCLUSION:\n\n1. Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n\n   Or\n\n   Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n2. Karnofsky\u002FLansky score of 50% or greater\n3. Pulse Ox greater than or equal to 90% on room air\n4. AST less than 5 times upper limit of normal (less than 10 times upper normal if known with metastatic liver disease)\n5. Total bilirubin less than 3 times the upper limit of normal\n6. Serum creatinine less than 3 times upper limit of normal\n7. Available autologous T-cells with greater than or equal to 20% expressing GD2.CAR\n8. Informed consent and assent (as applicable) obtained from parent\u002Fguardian and child.\n9. Greater than 1 year of age.\n10. Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study.\n\nTREATMENT EXCLUSION:\n\n1. History of hypersensitivity to murine protein containing products (patients who have undergone desensitization and successful re-challenge without hypersensitivity reaction are eligible).\n2. Known presence of Human Anti-Mouse Antibodies (HAMA).\n3. Tumor potentially causing airway obstruction per investigator discretion.\n4. Pregnancy or lactation \u002F will not use birth control methods.\n5. Currently receiving immunosuppressive drugs (patients on low dose corticosteroids are eligible: less than 0.25 mg\u002Fkg\u002Fday of prednisone\u002Fequivalent).\n6. Primary brain tumor or known brain metastases (on evaluation by MIBG and\u002For PET if applicable, CT\u002FMRI\u002FLP not required).","ALL","1 Year","24 Years",{"count":20,"type":21},27,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","The purpose of this study is to find the largest safe dose of i15.NKG2D.zeta-NK cells in combination with C7R.GD2.CAR-T cells, and additionally to evaluate how long they can be detected in patients' blood and what affect they have on patients' cancer.\n\nPatients eligible for this study have neuroblastoma or osteosarcoma that expresses a substance on the cancer cells called GD2. This cancer has either come back after treatment or did not respond to the standard or other investigational treatments or therapies used to treat it. There is no standard treatment for these types of advanced cancers at this time. This is a gene transfer research study using special immune cells called NK cells and T cells. NK cells and T cells are types of white blood cell that help the body fight infection.\n\nThe body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: NK cells and T cells. T cells are special infection-fighting blood cells that can kill cells infected with viruses and tumor cells. NK cells, another kind of infection-fighting cell, can recognize a wide range of cells in distress, including tumor cells and cells that help protect tumor cells in the cancer environment. Both NK cells and T cells have been used individually to treat patients with cancers. They have shown promise, but have not been strong enough individually to cure most patients.\n\nInvestigators have found from previous research that we can put a new gene into T cells that will make them recognize GD2, a substance found on almost all neuroblastoma and osteosarcoma cells. We can also put a new gene into NK cells that help them fight the tumor environment. Investigators know that T cells and NK cells need substances called cytokines to survive but the cells do not get enough cytokines after infusion into the body; therefore, the investigators have added the genes C7R and IL15 into the T and NK cells, respectively, to give each cell a constant supply of cytokine that helps them to survive longer.\n\nThe C7R.GD2.CAR-T cells and i15.NKG2D.zeta-NK cells are investigational products not approved by the Food and Drug Administration.",[27,28,29,30],"Relapsed Neuroblastoma","Refractory Neuroblastoma","Relapsed Osteosarcoma","Refractory Osteosarcoma",[32,33,34,35,36,37,38],"Gene Therapy","CAR T cells","Neuroblastoma","Osteosarcoma","Immunotherapy","chimeric antigen receptor","NK Cell","NOT_YET_RECRUITING","2026-06-30",{"date":42,"type":43},"2026-07-01","ACTUAL",{"date":45,"type":21},"2026-08",{"date":47,"type":21},"2044-04",{"name":49,"class":50},"Baylor College of Medicine","OTHER",1,{"id":53,"slug":54,"hasResults":11,"nctId":55,"briefTitle":56,"officialTitle":57,"acronym":58,"eligibilityCriteria":59,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":60,"enrollmentInfo":61,"targetDuration":4,"studyType":22,"phases":63,"briefSummary":65,"conditions":66,"keywords":71,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":76,"lastUpdatePostDateStruct":77,"startDateStruct":79,"completionDateStruct":81,"leadSponsor":83,"locationsCount":85},"100571548","phase-1-peel-224-vincristine-and-temozolomide-in-pediatric-solid-tumors-100571548","NCT06721689","PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors","A Phase 1\u002F2 Clinical Trial of the Novel Topoisomerase I Inhibitor PEEL-224 as a Single Agent and in Combination With Vincristine and Temozolomide in Children With Refractory, Progressive or Relapsed Solid Tumors","PEEL-224","Inclusion Criteria:\n\n1. Age:\n\n   * Phase 1: Age greater than or equal to 1 year and less than or equal to18 years\n   * Phase 2 Neuroblastoma (NBL) cohort: Age greater than or equal to 1 year and less than or equal to 30 years\n   * Phase 2 Rhabdomyosarcoma (RMS) cohort: Age greater than or equal to 1 year and less than or equal to18 years\n2. Diagnosis of:\n\n   * Phase 1: Refractory, progressive or relapsed non-central nervous system (CNS) solid tumors who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse\n   * Phase 2: Refractory, progressive or relapsed neuroblastoma (NBL) or rhabdomyosarcoma (RMS) who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse.\n3. Disease status:\n\n   * Phase 1: evaluable or measurable disease\n   * Phase 2, subjects with Neuroblastoma (NBL): evaluable or measurable disease by International Neuroblastoma Response Criteria (INRC); subjects with only bone marrow disease are not eligible\n   * Phase 2, subjects with rhabdomyosarcoma (RMS): measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)1.1.\n4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (age greater than 16 years) or Lansky Performance Status of at least 60 (age less than 16 years).\n5. Females of childbearing potential must have a negative urine\u002Fserum pregnancy test.\n6. Adequate bone marrow function\n\n   Hematologic requirements for all subjects on phase 1 and subjects on phase 2 without malignant infiltration of the bone marrow:\n   * Absolute neutrophil count (ANC) greater than or equal to 750\u002Fmm3 (greater than or equal to 7 days since last dose of short acting myeloid growth factor medications (e.g. filgrastim) and greater than or equal to 14 days since last dose of long-acting myeloid medications (e.g. peg-filgrastim)\n   * Platelet count ≥ 75,000 mm3 (greater than or equal to 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days)\n   * Not refractory to packed red blood cell transfusions\n\n   Hematologic requirements for subjects on phase 2 with malignant infiltration of the bone marrow:\n   * Absolute neutrophil count (ANC) greater than or equal to 500\u002Fmm3 (greater than or equal to 7 days since last dose of short acting myeloid growth factor medications (e.g. filgrastim) and greater than or equal to 14 days since last dose of long-acting myeloid medications (e.g. peg-filgrastim))\n   * Platelet count greater than or equal to 50,000\u002Fmm3 (greater than or equal to 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days)\n   * Not refractory to packed red blood cell transfusions\n   * Patients on phase 2 with malignant infiltration of the bone marrow will not be evaluable for hematologic toxicity.\n7. Adequate renal function as evidenced by creatinine clearance as calculated by the Schwartz equation (see below), radioisotope glomerular filtration rate (GFR) greater than or equal to 70 mL\u002Fmin\u002F1.73 m2, or maximum serum creatinine as below:\n\n   Age Maximum Serum Creatinine (mg\u002FdL)\n\n   Male Female 1 to less than 2 years 0.6 0.6 2 to less than 6 years 0.8 0.8 6 to less than 10 years 1 1 10 to less than 13 years 1.2 1.2 13 to less than 16 years 1.5 1.4 greater than 16 years 1.7 1.4 Threshold derived from the Schwartz formula for estimating glomerular filtration rate (GFR) (Schwartz et al., J.Peds, 106:522,1985) utilizing child length and stature data published by the CDC The Schwartz equation for subjects less than 18 years of age: eGFR (mL\u002Fmin\u002F1.73 m2) = 0.413 x \\[height (cm)\u002Fserum creatinine (mg\u002FdL)\\]\n8. Adequate liver function\n\n   * Aspartate Aminotransferase (AST\u002FSGOT): less than or equal to 3 times the upper limit of normal (ULN) or less than or equal to 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the upper limit of normal (ULN) for Aspartate Aminotransferase (AST) is 50 U\u002FL.\n   * Alanine Aminotransferase (ALT\u002FSGPT): less than or equal to 3 times the ULN or less than or equal to 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the upper limit of normal (ULN) for Alanine Aminotransferase (ALT) is 45 U\u002FL.\n   * Total bilirubin: less than or equal to 1.5 times the upper limit of normal with the exception of patients with Gilbert's syndrome who must have bilirubin less than 3X institutional upper limit of normal (ULN).\n9. Prior Therapy: Patients must have had resolution of acute toxic effects of prior therapy to grade less than or equal to 1 according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v 5.0 except organ function as noted above, adverse events (AE) that are considered clinically non-significant (i.e. alopecia), or controlled on supportive care (i.e. nausea\u002Fvomiting, hypothyroidism). Patients must meet the following minimum washout periods prior to enrollment:\n\n   * Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy\n   * Small molecule targeted therapy: At least 7 days following the last dose of a small molecule targeted agent.\n   * Antibody therapy: At least 21 days following the last dose of antibody including anti-GD2 monoclonal antibody.\n   * Cellular therapy: At least 42 days following completion of a cellular therapy agent (e.g. modified T cells, NK cells, dendritic cells)\n   * Autologous hematopoietic stem cell transplant and stem cell boost: Subjects must be at least 60 days from day 0 of an autologous stem cell transplant or stem cell boost.\n   * Myeloid growth factors: At least 7 days following short-acting myeloid growth factor (e.g. filgrastim) and at least 14 days following the last dose of long-acting myeloid growth factor (e.g. peg-filgrastim)\n   * Thrombopoietin receptor agonists: At least 14 days following last dose of thrombopoietin receptor agonist such as romiplostim\n   * Interleukins, interferons, and cytokines (other than hematopoietic growth factors): At least 21 days following the completion of interleukins, interferon, or cytokines, including IL-2\n   * Radiotherapy:\n\n     * At least 14 days after limited field radiation therapy;\n     * At least 90 days after total body irradiation, craniospinal radiotherapy; or radiation to greater than 50% of pelvis;\n     * At least 42 days must have elapsed if other substantial BM radiation.\n   * Radiopharmaceutical therapy (e.g. radiolabeled antibody, 131I- MIBG): At least 42 days after radiopharmaceutical therapy\n   * Major Surgery: At least 2 weeks from prior major surgical procedure. Note: Biopsy, CNS shunt placement\u002Frevision, and central line placement\u002Fremoval are not considered major.\n   * Strong CYP1A2 and\u002For CYP3A4 inhibitors and\u002For inducers: At least 14 days following use of a strong CYP1A2 and\u002For CYP3A4 inhibitor and\u002For inducer. See Appendix 1 for examples. (Note that levofloxacin is permitted when clinically indicated)\n10. Prior treatment with irinotecan and\u002For temozolomide is permitted.\n11. Female patients of reproductive potential must agree to use a highly effective contraceptive method for the duration of study therapy and for at least six months after the final dose of PEEL-224. Males of reproductive potential with a female partner of child-bearing potential must use a highly effective for the duration of the study and for at least six months after the final dose of PEEL-224.\n12. Subjects must agree to use sun protective measures while receiving treatment and for 4 weeks after the last dose of PEEL-224\n13. Parental\u002Fguardian permission (informed consent) and if appropriate, child assent.\n\nExclusion Criteria:\n\n1. Prior treatment with PEEL-224.\n2. Subjects receiving any other anti-cancer agents.\n3. Subjects with primary central nervous system (CNS) solid tumors or central nervous system (CNS) metastatic disease.\n4. Subjects with prior allogeneic stem cell or solid organ transplantation.\n5. Pregnant or lactating females.\n6. Subjects with a known history of human immunodeficiency virus (HIV), hepatitis B, and\u002For hepatitis C (testing not required as part of screening).\n7. Subjects with symptomatic congestive heart failure.","30 Years",{"count":62,"type":21},59,[24,64],"PHASE2","The phase 1 primary objective is to determine the pediatric recommended phase 2 dose (RP2D) of PEEL-224 as a single agent (phase 1A) and in combination with vincristine and temozolomide (phase 1B). The phase 2 primary objective is to estimate the objective response rate (ORR) in children with refractory, progressive and relapsed NBL and rhabdomyosarcoma (RMS) treated with the RP2D of PEEL-224 in combination with vincristine and temozolomide.",[67,68,27,28,69,70],"Refractory Solid Tumors","Relapsed Solid Tumors","Relapsed Rhabdomyosarcoma","Refractory Rhabdomyosarcoma",[72,73,74],"Relapsed","Refractory","Solid Tumor","RECRUITING","2026-06-12",{"date":78,"type":43},"2026-06-15",{"date":80,"type":43},"2025-03-23",{"date":82,"type":21},"2031-04",{"name":84,"class":50},"Theodore Laetsch",7,{"id":87,"slug":88,"hasResults":11,"nctId":89,"briefTitle":90,"officialTitle":91,"acronym":92,"eligibilityCriteria":93,"healthyVolunteers":11,"sex":16,"minAge":94,"maxAge":95,"enrollmentInfo":96,"targetDuration":4,"studyType":22,"phases":98,"briefSummary":99,"conditions":100,"keywords":103,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":115,"lastUpdatePostDateStruct":116,"startDateStruct":118,"completionDateStruct":120,"leadSponsor":122,"locationsCount":51},"100631561","phase-1-dual-target-gd2b7-h3-car-nk-cells-for-pediatric-relapsed-or-refractory-neuroblastoma-100631561","NCT07502287","Dual-Target GD2\u002FB7-H3 CAR-NK Cells for Pediatric Relapsed or Refractory Neuroblastoma","A Phase 1\u002FPhase 2, Open-Label Study of BiomarkerInformed, Allogeneic Dual-Target GD2\u002FB7-H3 (CD276) CAR-NK Cells in Children and Young Adults With Relapsed or Refractory Neuroblastoma","DUAL-NK-NB","Inclusion Criteria:\n\n* Age 12 months to 21 years at consent\u002Fassent.\n* Histologically confirmed neuroblastoma or ganglioneuroblastoma with relapsed, refractory, progressive, or persistent high-risk disease for which no curative standard option is available.\n* Measurable or evaluable disease according to revised International Neuroblastoma Response Criteria (rINRC), including MIBG-avid disease, CT\u002FMRI-evaluable soft-tissue disease, and\u002For bone marrow disease.\n* Tumor material available for central assessment of GD2 and B7-H3 expression; at least one target must be positive.\n\nGD2 is treated as the core target and B7-H3 as the complementary target for correlative target-prioritization analyses.\n\n* Prior exposure to standard neuroblastoma therapy, including anti-GD2-based therapy, unless contraindicated, unavailable, or declined for a documented medical reason.\n* Lansky or Karnofsky performance score \\>= 50.\n* Life expectancy \\>= 8 weeks.\n* Recovery from clinically significant acute toxicities of prior therapy and protocol-defined washout from chemotherapy, biologics, radiation, and prior cell therapy.\n* Adequate organ function: hematologic, renal, hepatic, cardiac, and pulmonary function considered sufficient by protocoldefined laboratory and clinical thresholds.\n* Negative pregnancy test for patients of childbearing potential and agreement to use effective contraception during the protocol-defined period.\n* Written informed consent from parent\u002Flegal guardian and assent from the participant when appropriate.\n\nExclusion Criteria:\n\n* Active uncontrolled infection, including bacteremia, uncontrolled viral infection, or invasive fungal disease.\n* Pregnancy or breastfeeding.\n* Active grade \\>= 2 graft-versus-host disease, or systemic immunosuppression for treatment\u002Fprevention of graft-versushost disease within the protocol-defined washout period after prior allogeneic transplant.\n* Symptomatic or unstable central nervous system disease requiring urgent medical intervention.\n* Prior genetically modified cellular therapy within the protocol-defined washout window, or unresolved clinically significant toxicity from prior cell therapy.\n* Active autoimmune disease requiring systemic immunosuppressive therapy.\n* Clinically significant uncontrolled cardiovascular, pulmonary, hepatic, renal, or neurologic disorder that would increase study risk.\n* Known hypersensitivity to fludarabine, cyclophosphamide, study-product components, or supportive-care medications required by the protocol.\n* Known uncontrolled HIV infection or uncontrolled hepatitis B or C.\n* Any medical, psychosocial, or logistical condition that, in the investigator's judgment, would make study participation unsafe or would impair protocol adherence.","12 Months","21 Years",{"count":97,"type":21},36,[24,64],"This illustrative Phase 1\u002FPhase 2 study tests allogeneic dual-target GD2\u002FB7-H3 (CD276) CAR-NK cells in children and young adults with relapsed or refractory neuroblastoma. After lymphodepletion, participants receive IV CAR-NK cells;Part A defines the RP2D and Part B estimates preliminary activity",[27,28,101,102],"High-Risk Neuroblastoma","Ganglioneuroblastoma",[104,105,106,107,108,109,110,111,112,113,114],"pediatric neuroblastoma","CAR-NK","GD2","B7-H3","CD276","dual-targeting","relapsed\u002Frefractory","allogeneic","solid tumor immunotherapy","cell therapy","biomarkerinformed design","2026-03-25",{"date":117,"type":43},"2026-03-30",{"date":119,"type":43},"2026-03-02",{"date":121,"type":21},"2028-06-17",{"name":123,"class":124},"Beijing Biotech","INDUSTRY",{"id":126,"slug":127,"hasResults":11,"nctId":128,"briefTitle":129,"officialTitle":130,"acronym":131,"eligibilityCriteria":132,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":133,"targetDuration":4,"studyType":22,"phases":135,"briefSummary":136,"conditions":137,"keywords":138,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":139,"lastUpdatePostDateStruct":140,"startDateStruct":142,"completionDateStruct":144,"leadSponsor":146,"locationsCount":148},"100618644","phase-1-a-multi-arm-platform-trial-for-relapsed-neuroblastoma-100618644","NCT07334301","A Multi-Arm, Platform Trial For Relapsed Neuroblastoma","A Multi-Arm, Multi-Stage Platform Trial For Relapsed Neuroblastoma","BEACON2","Inclusion Criteria:\n\n* Disease specific\n\n  * Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS)\\[1\\] definition\n  * High risk relapsed neuroblastoma (relapsed or progressed after being defined as High Risk at any time following diagnosis or progressed\u002Frelapsed as high-risk neuroblastoma)\n  * Measurable disease by cross sectional imaging or evaluable disease (uptake on MIBG scan with or without bone marrow histology), as per INRC \\[2, 3\\]. Participants with only bone marrow detectable disease (bone marrow aspirate or trephine) are NOT eligible for the study General\n  * Age ≥1 year\n  * Signed informed consent from participant, parent or guardian Performance and organ function\n  * Performance Status\n\n    o Lansky (for patients ≤12 years of age) or Karnofsky (for those \\>12) ≥ 50%, (Participants who are unable to walk because of paralysis, but who are able to sit upright unassisted in a wheelchair, will be considered ambulatory for the purpose of assessing performance score)\n  * Life expectancy of ≥12 weeks\n  * Bone marrow function (within 72 hours prior to randomisation):\n\n    * Platelets ≥ 50 x 109\u002FL (unsupported for 72 hours)\n    * ANC ≥ 0.50 x 109\u002FL (no G-CSF support for 72 hours)\n    * Haemoglobin \\> 8 g\u002FdL (transfusions allowed)\n  * Renal function (within 72 hours prior to randomisation):\n\n    * Absence of clinically significant proteinuria (either early morning urine dipstick ≤ 2+) or if dipstick urinalysis shows \\> 2+ proteinuria, protein: creatinine (Pr\u002FCr) ratio must be \\\u003C 0.5 or a 24 hour protein excretion must be \\\u003C 0.5g\n    * Serum creatinine ≤ 1.5 ULN for age, if higher, a measured GFR (radioisotope or 24 hour urine calculated creatinine clearance) must be ≥ 60 ml\u002Fmin\u002F1.73 m2\n  * Liver function (within 72 hours prior to randomisation):\n\n    o Absence of clinically significant signs of liver dysfunction. AST or ALT ≤ 3.0 ULN and total bilirubin ≤ 1.5 ULN. In patients with liver metastases, AST or ALT ≤ 5 ULN and total bilirubin ≤ 2.5 ULN is allowed.\n  * Coagulation:\n\n    * Participants must not have an active uncontrolled coagulopathy.\n    * Anticoagulation is permitted as long as the INR or APTT is within therapeutic limits (according to the medical standard of the institution) and the participant has been on a stable dose of anticoagulants for at least two weeks at the time of study enrolment.\n  * Blood pressure below 95th centile for age and sex. Participants ≥18 years of age should have a blood pressure ≤150\u002F90 mmHg (within 72 hours prior to randomisation). Use of antihypertensive medication is permitted.\n\nTier 2 Specific Inclusion Criteria\n\n• More than one relapse event or ineligible for Tier 1.\n\nNB- The following previous treatments are allowed provided that the principal investigator expects a favourable benefit\u002Frisk assessment (e.g. patients could derive potential benefit from the Tier 2 combination):\n\n* bevacizumab,\n* any anti-GD2 antibody given with chemotherapy ('chemo-immunotherapy')\n* previous treatment with temozolomide with irinotecan\n\nExclusion Criteria:\n\n* • Known contraindication or hypersensitivity to:\n\n  * Any study drug or component of the formulation\n  * Chinese hamster ovary products or other recombinant human or humanised antibodies.\n  * Participants with mild previous hypersensitivity reactions to anti-GD2 antibodies may be included, but those with severe (or G4) hypersensitivity reactions to anti-GD2 antibodies will be excluded.\n\n    * Clinically significant neurological toxicity, uncontrolled seizures or objective peripheral neuropathy (\\> grade 2). (Unresolved neurological deficits from previous spinal cord compression or surgeries are acceptable). Participants with previous ≥ Grade 3 motor neurotoxicity secondary to anti-GD2 are excluded, even if recovered\n    * Prior severe arterial thrombo-embolic events (e.g. cardiac ischemia, cerebral vascular accident, peripheral arterial thrombosis) or any ongoing arterial thrombo-embolic events\n    * A history of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.\n    * Patients that are allergic to all therapies for Pnemocystis jirovecii pneumonia and can thus not receive prophylaxis for PJP\n    * Uncontrolled infection\n    * Inadequate recovery from prior surgery with ongoing ≥ Grade 3 surgical complications. Grade ≥ 2 wound dehiscence.\n    * Recent surgical procedures (at start of trial treatment). Patient can be randomised up to 48hr prior to these periods being completed provided that trial treatment only starts after complying with all of them:\n  * Core biopsies within previous 24hr\n  * Open excisional biopsies within previous 48hr\n  * Major surgery within previous 2 weeks\n  * Bone marrow aspirates\u002Ftrephines, within previous 48hr\n  * Tunnelled central line insertion within previous 48hr\n\n    • Washout from prior treatments (at start of trial treatment):\n  * Chemotherapy within previous 2 weeks (1 week for oral metronomic chemotherapy regimens)\n  * Any anti-GD2 therapy within previous 2 weeks\n  * Craniospinal radiotherapy or MIBG therapy within previous 6 weeks\n  * Radiotherapy to the tumour bed within previous 2 weeks (no washout for palliative radiotherapy)\n  * Myeloablative therapy with haematopoietic stem cell rescue (autologous stem cell transplant) within previous 8 weeks\n  * Allogeneic stem cell transplant within previous 12 weeks (with absence of active ≥ G2 acute GVHD)\n  * 14 days or 5 half-lives (whichever occurs later) from last administration of an IMP in an IMP-trial\n\n    * Bleeding metastases (participants with CNS metastases can be enrolled as long as the metastases are not bleeding). At least 6 months from any ≥ G3 haemoptysis or pulmonary haemorrhage\n    * Use of enzyme inducing anticonvulsants within 72hr of start of trial treatment\n    * Conditions that increase the risk of bevacizumab-related toxicities:\n  * History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation)\n  * History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to study enrolment\n  * Current chronic intestinal inflammatory disease\u002Fbowel obstruction\n\n    * Intolerance to galactose and fructose, lactase deficiency, and\u002For defect of absorption of galactose and fructose\n    * Males or females of reproductive potential may not participate unless they agree to use a highly effective method of birth control, i.e. with a failure rate of less than 1% per year, (e.g. implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner), for the duration of study therapy and for up to 6 months after the last dose of trial drugs. A negative urine or serum pregnancy test must be obtained within 72 hours prior to dosing in females who are post-menarche.\n    * Pregnant or lactating participant\n    * Live or live-attenuated vaccines given within previous 28 days prior to study enrolment\n    * Any uncontrolled medical condition that poses an additional risk to the participant\n\nTier 1 Specific Exclusion Criteria\n\n* More than one relapse\u002Fprogression event after the start of high risk neuroblastoma therapy\n* Previous treatments that are not allowed\n\n  * Bevacizumab for relapsed neuroblastoma. Patients who have received BIT for refractory disease are not excluded, providing no progression of disease during this treatment occurred\n  * Treatment with any anti-GD2 antibody given with chemotherapy ('chemo-immunotherapy') for treatment of relapsed neuroblastoma. Prior treatment with chemo-immunotherapy for refractory disease is allowed, provided no disease progression during this therapy.",{"count":134,"type":21},160,[24,64],"Neuroblastoma is one of the most common solid childhood tumours, and a major cause of cancer-related death in children. More than 1200 children\u002Fyoung adults a year are diagnosed in USA and Europe. Around 600 of these cases are considered high-risk, which means the cancer is more difficult to treat successfully. Despite improvements in survival over recent decades, a significant proportion of patients with high-risk neuroblastoma have disease that does not respond to standard treatments (refractory neuroblastoma) or comes back after completion of standard frontline treatment (relapsed neuroblastoma). Therefore, there is a need to develop new treatment strategies and test new drugs to improve outcomes for children with neuroblastoma.\n\nAims Of The BEACON2 Trial\n\n* To improve survival for patients with relapsed neuroblastoma by developing new treatment combinations\n* To evaluate new treatment combinations in relapsed neuroblastoma, within a phase I\u002FII trial that can impact clinical practice, while also allowing dose confirmation for new promising combinations\n* To evaluate the safety, activity, efficacy and impact on quality of life of these new treatment combinations in relapsed neuroblastoma patients\n* To improve our understanding of relapsed neuroblastoma biology and advance the development of targeted therapies using biomarkers, by conducting a comprehensive biomarker sample collection.\n\nTrial Design BEACON2 is a randomised phase I\u002Fphase II, open label, international trial. The trial will have two tiers: Tier 1 will be the main randomisation for two treatment arms initially. Participants will be randomised at trial entry to receive one of the available regimens, treatment A or treatment B. Tier 2 will include smaller dose expansion\u002Fconfirmation cohorts for more novel experimental treatment combinations (Arm C and future arms), with the potential for them to be moved to Tier 1.\n\nCurrent Tier 1 (Randomisation Tier) Treatment Arms in the BEACON2 Trial:\n\nArm A: dbIT Treatment with dinutuximab beta, irinotecan, and temozolomide, 3 weekly x12 cycles Arm B: BIT Treatment with bevacizumab, irinotecan, and temozolomide, 3 weekly x12 cycles\n\nCurrent Tier 2 (Registration Only Tier) Treatment Arms in the BEACON2 Trial:\n\nArm C: dbBIT Treatment with dinutuximab beta, bevacizumab, irinotecan, and temozolomide, 3 weekly x12 cycles\n\nPatient Population and Sample Size Patients aged ≥1 years of age with relapsed neuroblastoma. For each arm in Tier 1, up to 75 patients will be recruited to complete phase 2 investigations. For each arm in Tier 2, 10 patients will be recruited to complete phase I investigations. Approximately 160 participants are initially planned, 75 in each arm of Tier 1 and 10 participants for one dose-confirmation cohort in Tier 2.\n\nThe study is expected to recruit patients for 3 years, and then finish patient follow-up after an additional 5 years.\n\nTranslational Sub-study \u002F Biological Studies\n\nIt is standard of care for patients diagnosed with relapsed neuroblastoma to:\n\n* Have had a tumour sample collected at point of initial diagnosis (either during biopsy or surgery)\n* Have bloods collected before they start and during treatment for their relapsed neuroblastoma\n* Have a bone aspirate\u002Ftrephine procedure in order to help confirm relapse. These samples provide very important opportunities for further research, and the study investigators would like to make full use of these opportunities by collecting the analysis already performed on these samples and collect some additional samples (at the same time as the standard ones) to learn and understand more about neuroblastoma and its treatment. Samples will undergo research analysis at the national SIOPEN reference laboratories.",[27],[34],"2026-01-05",{"date":141,"type":43},"2026-01-12",{"date":143,"type":43},"2024-11-11",{"date":145,"type":21},"2030-12-31",{"name":147,"class":50},"University of Birmingham",23,{"id":150,"slug":151,"hasResults":11,"nctId":152,"briefTitle":153,"officialTitle":154,"acronym":4,"eligibilityCriteria":155,"healthyVolunteers":11,"sex":16,"minAge":94,"maxAge":156,"enrollmentInfo":157,"targetDuration":4,"studyType":22,"phases":159,"briefSummary":160,"conditions":161,"keywords":163,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":164,"lastUpdatePostDateStruct":165,"startDateStruct":167,"completionDateStruct":169,"leadSponsor":171,"locationsCount":173},"100577867","phase-1-study-of-halkcar-t-cells-for-patients-with-relapsedrefractory-high-risk-neuroblastoma-100577867","NCT06803875","Study of hALK.CAR T Cells for Patients With Relapsed\u002FRefractory High-risk Neuroblastoma","A Phase 1\u002F2 Study of hALK.CAR T Cells for Patients With Relapsed\u002FRefractory High-risk Neuroblastoma","Inclusion Criteria:\n\n1. Age ≥ 12 months and \\\u003C 30 years at the time of consent. The first patient on each dose level will need to be age ≥ 6 years old\n2. Disease Status:\n\n   1. Patients must have histologic verification of neuroblastoma at diagnosis or at relapse\n   2. Patients must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at time of study enrollment\n   3. Patients must have persistent\u002Frefractory or relapsed disease for which standard curative measures are no longer effective, as defined in the protocol\n   4. Patients must have evaluable or measurable disease per the revised International Neuroblastoma Response Criteria (INRC)\n3. Adequate washout from prior treatment regimens\n4. Adequate organ function\n5. Adequate performance status defined as Lansky or Karnofsky performance score ≥50%\n6. Subjects of reproductive potential must agree to use acceptable birth control methods\n7. Signed informed consent\n\nExclusion Criteria:\n\n1. Pregnant or nursing (lactating) women\n2. Patients with uncontrolled active infection\n3. Patients who are concurrently receiving other investigational agents\n4. Patients who have received prior CART-cell or other gene-modified immune-effector cell therapy, are not eligible unless they are \\>8 weeks from time of infusion, have fully recovered from any associated toxicities and have documented lack of persistence of the product\n5. Patients with a known additional malignancy other than non-melanomatous skin cancer or carcinoma in situ, unless not requiring active treatment and stable or disease-free for at least 3 years\n6. Uncontrolled CNS metastasis\n7. CNS disorder such as cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement which may impair the ability to evaluate neurotoxicity\n8. History of severe hypersensitivity reaction to compounds used in the study\n9. HIV\u002FHBV\u002FHCV infection\n10. Patients receiving systemic steroid therapy (physiologic replacement, inhaled steroids and premedication for blood products are allowed)\n11. Primary immunodeficiency or history of systemic autoimmune disease requiring systemic immunosuppression\u002Fdisease modifying agents within the last 2 years\n12. Uncontrolled intercurrent illness\n13. Inability to comply with the study requirements","29 Years",{"count":158,"type":21},42,[24,64],"This Phase 1\u002F2 trial aims to determine the safety and feasibility of administration of autologous chimeric antigen receptor (CAR) T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor in pediatric subjects with relapsed or refractory neuroblastoma (NB).\n\nThe trial will be conducted in two phases:\n\nPhase 1 will determine the maximum tolerated dose (MTD) of autologous hALK.CAR T cells using a 3+3 dose escalation design. Phase 2 will be an expansion phase to determine rates of response to hALK.CAR T cells.",[27,28,162],"High-risk Neuroblastoma",[27,28,101],"2025-12-24",{"date":166,"type":43},"2025-12-26",{"date":168,"type":43},"2025-01-31",{"date":170,"type":21},"2029-12-31",{"name":172,"class":50},"Roberto Chiarle",2,{"id":175,"slug":176,"hasResults":11,"nctId":177,"briefTitle":178,"officialTitle":179,"acronym":180,"eligibilityCriteria":181,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":182,"targetDuration":4,"studyType":22,"phases":184,"briefSummary":185,"conditions":186,"keywords":4,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":164,"lastUpdatePostDateStruct":189,"startDateStruct":191,"completionDateStruct":193,"leadSponsor":195,"locationsCount":51},"100489256","phase-1-gpc2-car-t-cells-for-relapsed-or-refractory-neuroblastoma-and-metastatic-retinoblastoma-100489256","NCT05650749","GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma","Phase 1 Trial of GPC2-Directed Chimeric Antigen Receptor Autologous T Cells (GPC2 CAR T) for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma","GPC2","Neuroblastoma Inclusion Criteria:\n\n1. Patients must be ≥ 1 year of age\n2. Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible.\n3. Patients must have a previously histologically confirmed diagnosis of neuroblastoma:\n\n   1. That is recurrent\u002Frelapsed or refractory\u002Fpersistent according to INRC AND\n   2. For which standard curative measures do not exist or are no longer effective.\n   3. patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma.\n4. Patients must have evaluable or measurable disease at enrollment.\n5. In addition, patient must have experienced at least one of the following:\n\n   a. New disease site documented on at least one of the following: i. 123I-meta-iodobenzylguanidine (MIBG) or 18F-mFBG (meta-fluorobenzylguanidine) scan; OR ii. CT\u002FMRI; OR iii. FDG or Ga-68 Dotatate PET (in patients known to have MIBG non-avid tumor) and MRI findings consistent with tumor (i.e., bone lesions), OR iv. Biopsy confirmed neuroblastoma for any new or progressing lesion. b. Greater than 20% increase in a least one dimension of soft tissue mass documented by CT\u002FMRI and a minimum absolute increase of 5 mm in longest dimension in existing lesion(s). Previously irradiated lesions may be included.\n\n   c. Bone marrow biopsy shows progressive disease according to the revised INRC d. Stable persistent disease, such that response at the completion of upfront therapy or salvage therapy is less than partial response AND has a biopsy of at least one site showing viable neuroblastoma.\n\n   e. Responding persistent disease, defined as at least a partial response to frontline therapy (i.e., at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT\u002FMRI, or bone marrow aspirations\u002Fbiopsies). Patients in this category are required to have histologic confirmation of viable neuroblastoma from at least one residual site (tumor seen on routine bone marrow morphology is sufficient).\n6. Patients must have a Lansky (≤ 16 years) or Karnofsky (\\> 16 years) score of ≥ 60\n7. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.\n8. Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease)\n9. Aspartate aminotransferase (AST) ≤ 2.5 ULN (exception: AST ≤ 5 x ULN for patients with liver metastases).\n10. Alanine aminotransferase (ALT) ≤ 2.5 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).\n11. Patients must have a baseline pulse oximetry of at least 92% on room air. In addition, a DLCO ≥ 60% (corrected for anemia) is required if PFTs are clinically appropriate as determined by the treating investigator.\n12. Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist.\n\nNeuroblastoma Exclusion Criteria:\n\n1. Patients with active hepatitis B or active hepatitis C.\n2. Patients with HIV infection.\n3. Patients with uncontrolled active infection.\n4. Patients with primary or acquired immunodeficiency disorder.\n5. Patients with a known hypersensitivity to DMSO.\n6. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.\n7. Patients with actively progressing CNS metastases, including parenchymal or leptomeningeal involvement. (Note: CNS imaging at screening is only required if the there is a clinical indication of suspected CNS metastasis)\n8. Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and\u002For neurotoxicity.\n9. Patients with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.\n10. Patients who have received any live vaccines within 30 days prior to enrollment.\n11. Patients who are pregnant or nursing (lactating).\n12. Patients who have a life expectancy \\\u003C 6 months at time of consent.\n\nRetinoblastoma Inclusion Criteria:\n\n1. Patient age ≥ 6 months.\n2. Patients must have metastatic retinoblastoma according to International\n\n   Retinoblastoma Staging System (IRSS) risk classification (4) at the time of study enrollment:\n\n   a. Retinoblastoma Cohort 1 (Extra-CNS metastasis) i. Stage IVa disease ii. Extra-CNS disease must be confirmed as retinoblastoma by histology (either at diagnosis or recurrence) iii. Measurable disease: Defined as \\> 1cm2 or biopsy-proven bone marrow disease iv. Prior treatment: Recurrent or refractory disease following treatment with COG ARET0321-like or equivalent regimen as part of upfront or recurrent therapy b. Retinoblastoma Cohort 2 (CNS disease) i. Stage IVb disease ii. Histologic confirmation is not required iii. CNS disease defined as measurable disease \\>1cm2, non-measurable, or CSF positivity alone c. Prior treatment: i. Stage IVb.1 and IVb.2: Recurrent after treatment with COG ARET0321-like or equivalent regimen as part of upfront or recurrent therapy i. Stage IVb.3: Prior treatment is not required (i.e., eligible at initial diagnosis or recurrence)\n3. Patients must have a Lansky (≤ 16 years) or Karnofsky (\\> 16 years) score of ≥ 60\n4. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN .\n5. Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease)\n6. Aspartate aminotransferase (AST) ≤ 2.5 ULN (exception: AST ≤ 5 x ULN for patients with liver metastases).\n7. Alanine aminotransferase (ALT) ≤ 2.5 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).\n8. Patients must have a baseline pulse oximetry of at least 92% on room air. In addition, a DLCO ≥ 60% (corrected for anemia) is required if PFTs are clinically appropriate as determined by the treating investigator.\n9. Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist.\n\nRetinoblastoma Exclusion Criteria:\n\n1. Patients with active hepatitis B or active hepatitis C.\n2. Patients with HIV infection.\n3. Patients with uncontrolled active infection.\n4. Patients with primary or acquired immunodeficiency disorder.\n5. Patients with a known hypersensitivity to DMSO.\n6. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.\n7. Active medical disorder that, in the opinion of the investigator, would substantially increase the risk to the subject.\n8. Patients with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.\n9. Patients who have received any live vaccines within 30 days prior to enrollment.\n10. Patients who are pregnant or nursing (lactating).\n11. Patients who have a life expectancy \\\u003C 6 months at time of consent.\n12. Retinoblastoma Cohort 1 (Extra-CNS disease):\n\n    1. Concurrent CNS disease (they may be eligible for Retinoblastoma Cohort 2)\n    2. Stage III disease (orbital or lymph node regional extension without other hematogenous metastases).\n13. Retinoblastoma Cohort 2 (CNS disease):\n\n    1. \"Bulky\" disease (\\>5 cm in diameter) within or compressing the brainstem or thalamus. Note: Tumors touching the brainstem\u002Fthalamus without evidence of compression and\u002For tumors in other CNS locations do not have a maximal size criterion.\n    2. If evidence of clinically significant increased intracranial pressure at time of relapse, patient must demonstrate improvement by time of enrollment.",{"count":183,"type":21},45,[24],"This is a first in human dose escalation trial to determine the safety of administering GPC2 CAR T cells in patients with advanced neuroblastoma or retinoblastoma.",[28,27,162,187,188],"Retinoblastoma","Metastatic Retinoblastoma",{"date":190,"type":43},"2025-12-29",{"date":192,"type":43},"2023-05-23",{"date":194,"type":21},"2030-01-30",{"name":196,"class":50},"Stephan Grupp MD PhD",{"id":198,"slug":199,"hasResults":11,"nctId":200,"briefTitle":201,"officialTitle":202,"acronym":203,"eligibilityCriteria":204,"healthyVolunteers":11,"sex":16,"minAge":94,"maxAge":4,"enrollmentInfo":205,"targetDuration":4,"studyType":22,"phases":207,"briefSummary":208,"conditions":209,"keywords":210,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":217,"lastUpdatePostDateStruct":218,"startDateStruct":219,"completionDateStruct":221,"leadSponsor":223,"locationsCount":51},"100470036","phase-1-allogeneic-expanded-gamma-delta-t-cells-with-gd2-chemoimmunotherapy-in-relapsed-refractory-neuroblastoma-or-refractory-relapsed-osteosarcoma-100470036","NCT05400603","Allogeneic Expanded Gamma Delta T Cells With GD2 Chemoimmunotherapy in Relapsed \u002FRefractory Neuroblastoma or Refractory\u002F Relapsed Osteosarcoma","A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory\u002F Relapsed, or Progressive Neuroblastoma or Refractory\u002F Relapsed Osteosarcoma","Aflac-NBL-2002","Inclusion Criteria:\n\n* Patients must be ≥ 12 months of age at the time of enrollment in the study.\n* Diagnosis: Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. (Bone marrow samples with positive catecholamines are acceptable as confirmation of neuroblastoma) OR histological confirmation of osteosarcoma at diagnosis\n* Response to prior therapy:\n\n  * High-risk neuroblastoma with refractory, relapsed or progressive disease, defined as:\n  * First or greater relapse of neuroblastoma following completion of aggressive multi- drug frontline therapy.\n  * First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy.\n  * Persistent\u002Frefractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) after at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).\n  * Note that this excludes patients initially considered low or intermediate-risk neuroblastoma that progressed to high-risk disease but the patient has not progressed after the diagnosis of high-risk neuroblastoma.\n  * Relapsed or refractory osteosarcoma that is not responsive to standard treatment\n* Disease Status\n\n  * Patients must have measurable or evaluable disease per revised INRC for subjects with neuroblastoma or measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with Osteosarcoma\n  * Performance Level:Patients must have a Lansky (≤16 years) or Karnofsky (\\>16 years) score of ≥50\n* Prior Therapy\n\n  * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy before study registration.\n\n    * Prior dinutuximab therapy is allowed regardless of prior response or progression on dinutuximab\n    * Prior temozolomide therapy is allowed\n    * Prior zoledronate is allowed\n    * Prior dinutuximab\u002Ftemozolomide\u002Firinotecan chemoimmunotherapy is allowed\n    * Prior T cell therapy is excluded\n* Organ Function Requirements:\n\n  * Hematologic Functions : Absolute Neutrofil count ≥750\u002FuL and platelet count ≥ 75,000\u002Fµl, transfusion independent .\n  * Renal Function: Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.\n  * Liver Function: Total bilirubin ≤ 1.5 x ULN for age and serum glutamic-pyruvic transaminase (SGPT) (ALT) ≤ 135 U\u002FL (≤ 3x ULN).\n  * Cardiac Function: Normal ejection fraction (≥ 55%) documented by either echocardiogram or radionuclide multigated acquisition scan (MUGA) evaluation OR Normal fractional shortening (≥ 27%) documented by echocardiogram\n  * Pulmonary Function: Normal pulmonary function with no evidence of dyspnea at rest, no exercise intolerance.\n\nExclusion Criteria:\n\n* Prior T cell therapy\n* Pregnancy, breast feeding, or unwillingness to use effective contraception during the study will not be entered on this study.\n* Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.\n* Patients with known active Central Nervous System (CNS) disease (excluding skull disease with intracranial extension). Patients with a history of CNS disease are required to have a brain CT and\u002F or MRI at study registration.\n* Patients with prior allogeneic stem cell transplant\n* Patients who are on hemodialysis\n* Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture negative, afebrile, and meet other organ function criteria\n* Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.\n* Patients with disease of any major organ system that would compromise their ability to withstand therapy.\n* Patients who have had to permanently discontinue Dinutuximab due to toxicity\n* Patients with serious, uncontrolled cardiac arrhythmias\n* Patients with a history of myocarditis\n* Patients who have received any live vaccines within 30 days before enrollment",{"count":206,"type":21},24,[24],"The goal of this clinical trial is to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate in children with refractory or recurrent neuroblastoma or refractory\u002F relapsed osteosarcoma as well as to define the toxicities of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate",[34,28,27,29,30],[211,212,213,214,215,106,216],"Gamma Delta T Cells","Dinutuximab","Temozolomide","Zoledronate","Irinotecan","chemoimmunotherapy","2025-12-19",{"date":166,"type":43},{"date":220,"type":43},"2023-11-06",{"date":222,"type":21},"2026-12",{"name":224,"class":50},"Emory University",{"id":226,"slug":227,"hasResults":11,"nctId":228,"briefTitle":229,"officialTitle":229,"acronym":4,"eligibilityCriteria":230,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":60,"enrollmentInfo":231,"targetDuration":4,"studyType":22,"phases":233,"briefSummary":234,"conditions":235,"keywords":237,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":239,"lastUpdatePostDateStruct":240,"startDateStruct":242,"completionDateStruct":244,"leadSponsor":246,"locationsCount":173},"100595076","phase-1-feasibility-study-of-prolonged-administration-of-naxitamab-irinotecan-and-temozolomide-for-patients-with-relapsed-or-refractory-neuroblastoma-100595076","NCT07027748","Feasibility Study of Prolonged Administration of Naxitamab, Irinotecan, and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma","Inclusion Criteria:\n\n* Histologic Diagnosis: Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines \\[i.e. \\> 2 x upper limit of normal (ULN)\\], at the time of initial diagnosis.\n* Relapsed or Refractory Disease Patients must have ONE of the following:\n\n  * 1\\) Any prior episode of recurrent high-risk disease following completion of frontline high-risk therapy. Patients may have received other lines of therapy for treatment of recurrent disease prior to enrolling to this trial.\n  * 2\\) Prior progressive high-risk disease during frontline high-risk therapy. Patients may have received other lines of therapy for treatment of progressive disease prior to enrolling to this trial.\n  * 3\\) Primary resistant\u002Frefractory disease (less than partial response by INRC) detected after the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, ANBL2131) that was treated with additional therapy with the goal of improving remission status prior to enrolling to this trial.\n* Documentation of Disease: Patients must have at least ONE of the following at the time of enrollment:\n\n  * 1\\) Measurable tumor on MRI or CT scan. Measurable is defined as ≥ 10 mm in at least one dimension (or 15 mm in short axis for lymph node) on spiral\u002Fhelical CT or MRI that is MIBG avid or demonstrates increased FDG uptake on PET scan.\n  * 2\\) MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one site. This site must represent disease recurrence or known refractory disease at a site not previously radiated.\n  * 3\\) In patients with known MIBG non-avid disease, FDG-avid lesion detected on FDG- PET scan with positive uptake at a minimum of one site. This site must represent disease recurrence or known refractory disease at a site not previously radiated.\n  * Of note, patients with isolated bone marrow only disease are NOT eligible for this trial.\n* Prior Therapy: Prior lines of anticancer therapy allowed as described in eligibility section above by disease status. Washout periods from prior therapy are as follows:\n\n  * Myelosuppressive chemotherapy: Last dose given 14 days prior to enrollment.\n  * Small molecule targeted therapies (anti-neoplastic agents including retinoids): Last dose given 7 days prior to enrollment.\n  * Monoclonal antibodies: Last given at least 7 days or 3 half-lives, whichever is longer, prior to enrollment.\n  * Radiation:\n\n    * Craniospinal irradiation: Last fraction received minimum of six weeks prior to enrollment\n    * All other radiation: Last fraction received minimum of 14 days prior to enrollment\n  * Hematopoietic stem cell transplant: Date of autologous stem cell infusion following myeloablative chemotherapy must have been a minimum of 12 weeks prior to enrollment. Patients are not eligible post allogeneic stem cell transplant.\n  * Cellular therapies (including CAR-T cells, NK cells, other related cellular therapies): 21 days from the last cellular therapy infusion prior to enrollment and recovery from all associated toxicities\n  * 131I-MIBG therapy: Last therapy received a minimum of 6 weeks prior to enrollment.\n* Age: Patients 1 - 30 years of age at the time of enrollment are eligible for this study.\n* Performance level: Patients must demonstrate adequate performance level as measured by Karnofsky ≥ 70% for patients aged 16 years or older, OR Lansky ≥ 70% for patients younger than 16 years. Please see Appendix A for performance score measurement.\n* Participants must meet the following organ and marrow function as defined below:\n* Adequate bone marrow function as defined as BOTH of the following:\n\n  * Peripheral absolute neutrophil count (ANC) ≥ 750\u002FuL. Must be more than 14 days from last administration of long-acting myeloid stimulating factor (e.g. pegfilgrastim) or 7 days from last administration of short- acting myeloid stimulating factor (e.g. filgrastim or sargramostim)\n  * Peripheral platelet count ≥ 75,000\u002FuL. Must be without support, defined as at least 7 days from last platelet transfusion and\u002For platelet stimulating agent.\n* Adequate renal function as defined as EITHER of the following:\n\n  * Radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2\n  * Serum creatinine based on age\u002Fsex as follows:\n  * Age Maximum Serum Creatinine (mg\u002FdL)\n\n    * 1 to \\\u003C 2 years Male 0.6 Female 0.6\n    * 2 to \\\u003C 6 years Male 0.8 Female 0.8\n    * 6 to \\\u003C 12 years Male 1.0 Female 1.0\n    * 12 to \\\u003C 13 years Male 1.2 Female 1.2\n    * 13 to \\\u003C 16 years Male 1.5 Female 1.4\n\n      ---≥ 16 years Male 1.7 Female 1.4\n    * The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR.\n* Adequate liver function defined as ALL of the following:\n\n  * Total bilirubin ≤ 1.5 x ULN for age\\*\n  * ALT ≤ 3.0 x ULN for age (≤ 135 U\u002FL). For the purpose of this study, the ULN for ALT is 45 U\u002FL\n  * Albumin \\> 3 g\u002FdL --\\*If patient has known Gilbert syndrome, direct bilirubin should be used to measure liver function instead of total bilirubin. Direct bilirubin must be within normal limits for age for these patients.\n* Adequate cardiac function measured by echocardiogram as defined as EITHER of the following:\n\n  * Shortening fraction of ≥ 27%\n  * Ejection fraction of ≥ 50%\n* Adequate blood pressure as defined by BOTH of the following:\n\n  * Patients must have \\\u003C Grade 2 hypertension AND\n  * Be on no more than one standing antihypertensive\n* Adequate pulmonary function: Patients must have adequate pulmonary function, defined as:\n\n  * No dyspnea at rest\n  * No exercise intolerance\n  * Room air O2 saturation \\>94%\n  * Not on chronic oxygen therapy\n* Adequate pancreatic function, defined as lipase \\\u003C 1.5 x ULN\n* Able to comply with protocol requirements\n* Adequate contraception: The effects of naxitamab on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, participants with potential to become pregnant or to impregnate a partner must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a participant become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform the treating physician immediately. Patients treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of protocol therapy.\n* Ability to understand and\u002For the willingness of their parent or legally authorized representative to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Chronic (more than 2 weeks duration) diarrhea \\> grade 1\n* Prior receipt of naxitamab\n* Untreated central nervous system (CNS) metastatic disease\n* Pregnant or currently breast feeding: Pregnant participants are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the parent with protocol therapy, participants planning to continue breastfeeding are excluded from the study.\n* Clinically significant arrhythmias, i.e. those that cause clinical symptoms or require medications for control of symptoms\n* Prior allergic reaction to irinotecan or temozolomide\n* Discontinuation of prior irinotecan or temozolomide due to unacceptable toxicity\n* Discontinuation of prior GD2 directed immunotherapy due to unacceptable toxicity other than allergic reaction\n* Serious intercurrent illness\n* Active uncontrolled infection\n* Existing major organ dysfunction CTCAE \\>Grade 2, except for hearing loss and hematological status, kidney, and liver function as described in eligibility criteria\n* Concomitant Medication Restrictions:\n\n  * Patients may not be receiving immunosuppressive medications including pharmacologic doses of glucocorticoids or immunomodulatory agents due to concern for inhibition of antibody effect. Local and inhaled steroid agents are permitted.\n  * Patients may not be receiving concurrent anti-cancer agents or radiotherapy.\n  * Patients may not have received valproic acid within 14 days prior to enrollment.\n  * Patients may not have received strong CYP3A4 inducers, strong CYP3A4 inhibitors, or strong UGT1A1 inhibitors within 14 days prior to enrollment.\n\n    * Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.",{"count":232,"type":21},18,[24],"This research is being done to investigate a treatment regimen of Irinotecan, Temozolomide, and Sargramostin, and an immunotherapy called Naxitamab and whether giving Naxitamab more slowly reduces the side effects for participants with relapsed or refractory neuroblastoma.\n\nThe name of the study drugs involved in this study are:\n\n* Naxitamab (A type of monoclonal antibody)\n* Irinotecan (A standard of care chemotherapy)\n* Temozolomide (A standard of care chemotherapy)\n* Sargramostim (A standard of care, granulocyte-macrophage colony stimulating factor)",[34,236,27,28],"Neuroblastoma Recurrent",[34,236,27,28,238],"Progressive Neuroblastoma","2025-07-11",{"date":241,"type":43},"2025-07-14",{"date":243,"type":43},"2025-06-27",{"date":245,"type":21},"2027-12-01",{"name":247,"class":50},"Steven DuBois, MD",{"id":249,"slug":250,"hasResults":11,"nctId":251,"briefTitle":252,"officialTitle":253,"acronym":254,"eligibilityCriteria":255,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":156,"enrollmentInfo":256,"targetDuration":4,"studyType":22,"phases":258,"briefSummary":259,"conditions":260,"keywords":4,"overallStatus":75,"whyStopped":4,"lastUpdateSubmitDate":261,"lastUpdatePostDateStruct":262,"startDateStruct":264,"completionDateStruct":266,"leadSponsor":268,"locationsCount":51},"100378755","phase-1-nk-cells-infusions-with-irinotecan-temozolomide-and-dinutuximab-100378755","NCT04211675","NK Cells Infusions With Irinotecan, Temozolomide, and Dinutuximab","A Phase I\u002FII Safety Lead in Study of Ex-Vivo Expanded Allogeneic Universal Donor TGFβi NK Cell Infusions in Combination With Irinotecan, Temozolomide, and Dinutuximab in Patients With Relapsed or Refractory Neuroblastoma: The Allo - STING Trial","STING","Inclusion Criteria:\n\n* Less than 30 years of age when registered on the study.\n* Patients must have a histologic verification of neuroblastoma (NBL) or ganglioneuroblastoma or NBL cells in bone marrow with or without elevated urine catecholamines.\n* Life expectancy \\>2 months, AND one of the following:\n\n  * Recurrent disease; or\n  * First episode of progressive disease (new lesion, increase in size, previous negative bone marrow) during initial multi-drug, induction myelosuppressive therapy; or\n  * Primary resistant\u002Frefractory disease (partial, mixed, stable response criteria met) after completing at least 4 cycles of induction multi-drug induction chemotherapy\n* One of the following:\n\n  * Patients must have measurable or evaluable tumor defined as: a) Measurable tumor on MRI or CT obtained within 4 weeks prior to study entry; Measurable is defined as ≥ 10mm in at least one dimension AND that has positive uptake on I-123 MIBG scan (\"MIBG avid\") or demonstrates increased FDG uptake on 18F-FDG PET-CT or PET-MRI (\"PET-avid\"); OR b) Evaluable tumor by I-123 MIBG scan within 4 weeks prior to study entry, defined as positive uptake at a minimum of one site;\n  * Measurable or evaluable disease must represent recurrent disease after therapy completion or progressive disease on therapy or refractory disease during induction;\n  * Patients with refractory disease that are not avid on MIBG scan and do not have increased FDG uptake on PET must have biopsy proven viable NBL;\n  * New soft tissue sites that are MIBG avid or PET avid do not require biopsy as long as initial histologically-confirmed NBL diagnosis prior to current therapy\n* Patients must have progressed during or following completion of frontline therapy. Agents considered to be a part of frontline therapy would include chemotherapy, radiation therapy, autologous stem cell transplantation, retinoids, immunotherapy with anti GD2 agents, cellular therapies, or I-131 MIBG, and frontline therapy is defined as any combination of these agents defined in published regimens or current cooperative group clinical trials for the successful treatment of that cancer. Therapy may not have been received more recently than the timeframes defined below:\n\n  * Myelosuppressive chemotherapy: At least 14 days since completion of myelosuppressive therapy\n  * Biologic: At least 7 days since completion of therapy with non-myelosuppressive biologic or retinoid\n  * Radiation: At least 4 weeks since completion of radiation to any site identified as a target lesion. Palliative radiation is allowed to sites not used to measure response\n  * Stem Cell Transplant (SCT): At least 6 weeks after autologous stem cell transplant or stem cell infusions as long as hematologic criteria have been met\n  * 131I-MIBG Therapy: At least 6 weeks after therapeutic MIBG treatment\n  * Cellular therapies: At least 6 weeks after any cellular therapy treatment (e.g., prior NK, CAR-T therapy)\n\nSubjects who have previously received anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging are eligible.\n\nSubjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads are eligible.\n\nNo treatment with irinotecan and\u002F or temozolomide within the last 6 months.\n\n* Adequate bone marrow function, defined as:\n\n  * Peripheral absolute neutrophil count (ANC) ≥500\u002FmicroL. Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days or short-acting myeloid growth factors (e.g., Neupogen) within 7 days of study entry.\n  * Platelet count ≥50,000\u002FmicroL (transfusion independent for at least 1 week)\n* Adequate renal function defined as:\n\n  * Creatinine clearance or estimated radioisotope GFR ≥70 ml\u002Fmin\u002F1.73m2 or\n  * Serum creatinine \\\u003C 2x upper limit of normal (ULN) based on age\u002Fgender\n* Adequate liver function defined as:\n\n  * Total bilirubin \\\u003C1.5x ULN for age AND\n  * SGPT (ALT) ≤5x ULN for age (or ≤225 U\u002FL). For purpose of this study, the ULN for SGPT (ALT) is 45 U\u002FL.\n* Adequate central nervous system function defined as:\n\n  * Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsants\n  * CNS toxicity ≤ Grade 2\n* Adequate cardiac function defined as:\n\n  * Shortening fraction of ≥ 27% by ECHO OR\n  * Ejection fraction ≥ 50% by ECHO or gated radionuclide study\n* Adequate pulmonary function defined as:\n\n  * No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry \\> 94% if there is a clinical indication for pulse oximetry\n\nExclusion Criteria:\n\n* Patients who are pregnant or breastfeeding\n* Patients with elevated catecholamines (\\>2x ULN) only.\n* Patients must not have received 0.5 mg\u002F kg\u002F day (prednisone equivalent) doses of systemic steroids for at least 7 days prior to enrollment.\n* Patients must not have received CYP3A4 inducer or inhibitor for at least 7 days prior to study enrollment.\n* Patients must not have been diagnosed with any other malignancy.\n* Patients must not have \\> Grade 2 diarrhea.\n* Patients must not have uncontrolled infection.\n* Patients with history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of anti-GD2 therapy.\n* Patients with a significant illness that is not covered by the exclusion criteria or that is expected to interfere with the action of study agents or to increase the severity of the toxicities experienced from the study treatment.",{"count":257,"type":21},31,[24,64],"This is a Phase 1 study with Phase 2 expansion cohort. Phase 1 will assess the safety and tolerability of universal donor TGFβi NK Cell in combination with irinotecan, temozolomide, and dinituximab. The phase 2 of the study will estimate the response to treatment.",[27,28],"2025-05-08",{"date":263,"type":43},"2025-05-13",{"date":265,"type":43},"2022-09-01",{"date":267,"type":21},"2027-12",{"name":269,"class":50},"Nationwide Children's Hospital"]