[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT03721068":3,"trial-entities:NCT03721068":127,"trial-summary:NCT03721068":131},{"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":21,"study_type":31,"primary_purpose":32,"phases":33,"enrollment_info":35,"interventions":38,"primary_outcomes":53,"secondary_outcomes":58,"sex":76,"minimum_age":77,"maximum_age":78,"healthy_volunteers":79,"eligibility_criteria":80,"std_ages":84,"locations":88,"central_contacts":119,"overall_officials":120,"references":122,"see_also_links":123},"NCT03721068","LCCC 1743-ATL","Study of CAR T-Cells Targeting the GD2 With IL-15+iCaspase9 for Relapsed\u002FRefractory Neuroblastoma or Relapsed\u002FRefractory Osteosarcoma","A Phase I Study of Autologous Activated T-Cells Expressing a 2nd Generation GD2 Chimeric Antigen Receptor, IL-15, and iCaspase9 Safety Switch Administered To Patients With Relapsed\u002FRefractory Neuroblastoma or Relapsed\u002FRefractory Osteosarcoma","RECRUITING","2044-06-19","2026-03","2026-03-27","2019-02-19","UNC Lineberger Comprehensive Cancer Center","OTHER",true,"The body has different ways of fighting infections and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are molecules that fight infections and protect your body from diseases caused by bacteria and toxic substances. Antibodies work by sticking to those bacteria or substances, which stops them from growing and causing bad effects. T cells are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been enough to cure most patients.\n\nThis multicenter study is designed to combine both T cells and antibodies in order to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells (CAR) cells targeted against the disialoganglioside (GD2) antigen that express Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9), also known as iC9.GD2.CAR.IL-15 T cells.","In previous studies, it has been shown that when T cells have part of an antibody attached to them, they are better at recognizing and killing cancer cells. The antibody that will be used in this study is called anti-GD2. This antibody floats around in the blood and can detect and stick to cancer cells called neuroblastoma cells because they have a substance on the outside of the cells called GD2. For this study, the anti-GD2 antibody has been changed so that instead of floating freely in the blood, it is now joined to the T cells. However, it is unknown how long the iC9.GD2.CAR.IL-15 T cells last in the body, so their chances of fighting cancer cells are not well known.\n\nTo improve the tumor-fighting power of GD2-CAR-T cells, two additional components were added to these cells. The IL-15 gene was added so that the GD2-CAR-T cells can attack tumor cells more effectively. Interleukin-15 (IL-15) is a chemical that cells use to communicate with one another. Other research using IL-15 in combination with CAR-T cells has shown there is an increase in the body's ability to allow the CAR-T cells to survive and grow in the body. The iC9 gene was added as an \"off switch\" so it can stop the activity of the GD2-CAR-T cells if there are any serious bad side effects. Bad side effects seen previously in patients receiving the GD2 antibody alone include pain. In this study, the \"stop switch\" can be used to turn off the GD2-CAR-T cells if you experience intense pain that does not respond to normal pain treatments.\n\nThe study will enroll a minimum of 10 adult subjects and 10 pediatric subjects; all subjects will undergo lymphodepletion chemotherapy prior to the cell infusion as outlined in the protocol.",[19,20],"Neuroblastoma","Osteosarcoma",[22,23,24,25,26,27,28,29,30],"Autologous Chimeric Antigen Receptor (CAR) T Cells","Interleukin (IL)-15","Disialoganglioside (GD2)","Caspase 9","Pediatric","Rimiducid","AP1903","modified T cells","CAR T","INTERVENTIONAL","TREATMENT",[34],"PHASE1",{"count":36,"type":37},18,"ESTIMATED",[39,44,49],{"type":40,"name":41,"description":42,"armGroupLabels":43},"BIOLOGICAL","iC9.GD2.CAR.IL-15 T-cells","Three dose levels are being evaluated: 0.5 x 10\\^6, 1.0 x 10\\^6, 1.5 x 10\\^6",[41],{"type":45,"name":46,"description":47,"armGroupLabels":48},"DRUG","Cyclophosphamide","500 mg\u002Fm\\^2 IV dose on days 1-2 for lymphodepletion prior to cell infusion",[41],{"type":45,"name":50,"description":51,"armGroupLabels":52},"Fludarabine","30 mg\u002Fm\\^2 IV dose on days 1-4 for lymphodepletion prior to cell infusion",[41],[54],{"measure":55,"description":56,"timeFrame":57},"Number of participants with adverse events as a measure of safety and tolerability of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma or relapsed\u002Frefractory osteosarcoma","Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (AEs) (CTCAE, version 5.0), a descriptive terminology which can be utilized for AE reporting. A grading (severity) scale is provided for each AE term\u002Fsymptom: Grade 1 (Mild; asymptomatic); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE). Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).","4 weeks",[59,62,66,70,73],{"measure":60,"description":61,"timeFrame":57},"Identify the maximum tolerated dose (MTD) of iC9.GD2.CAR.IL-15 T cells administered to pediatric subjects with relapsed or refractory neuroblastoma or relapsed\u002Frefractory osteosarcoma","Tolerability of iC9.GD2.CAR.IL-15 T cells will be assessed by NCI-CTCAE criteria and the CRS grading criteria outlined in Section 12.4 and neurotoxicity\u002FICANS will be graded according to criteria outlined in Section 12.5",{"measure":63,"description":64,"timeFrame":65},"Expansion and persistence of iC9.GD2.CAR.IL-15 cells in vivo","Persistence of iC9.GD2.CAR.IL-15 T cells in vivo will be determined by quantitative Polymerase chain reaction (PCR) and flow cytometry in peripheral blood samples","15 years",{"measure":67,"description":68,"timeFrame":69},"Anti-tumor response rate to iC9.GD2.CAR.IL-15 t cell administration in pediatric subjects with relapsed or refractory neuroblastoma per Revised International Neuroblastoma Response Criteria (INCR) or relapsed\u002Frefractory osteosarcoma by RECIST v1.1","The overall response rate (ORR = complete (CR) + partial (PR) + minor (MR) responses) to iC9.GD2.CAR.IL-15 T cell infusion will be determined using the revised International Neuroblastoma Response Criteria (INRC) for subjects with neuroblastoma. The overall response rate (ORR = complete (CR) + partial (PR) responses) for subjects with osteosarcoma will be measured using Response evaluation criteria in solid tumors (RECIST) version 1.1","6 weeks",{"measure":71,"description":72,"timeFrame":65},"Overall survival (OS) in pediatric subjects with relapsed or refractory neuroblastoma or relapsed\u002Frefractory osteosarcoma treated with iC9.GD2.CAR.IL-15 T cells","OS will be measured from the date of administration of iC9.GD2.CAR.IL-15 T cells to the date of death",{"measure":74,"description":75,"timeFrame":65},"Progression free survival (PFS) in pediatric subjects with relapsed or refractory neuroblastoma or relapsed\u002Frefractory osteosarcoma treated with iC9.GD2.CAR.IL-15 T cells","PFS is defined from the date of administration of iC9.GD2.CAR.IL-15 T cells to the date of signs and symptoms of treatment failure or relapse from CR or PR, or death from any cause.","ALL","18 Months",null,false,{"inclusion":81,"exclusion":82,"raw_text":83},[],[],"All clinical and laboratory data required for determining eligibility must be available in the subject's medical\u002Fresearch record which will serve as the source document.\n\nBecause of the nature of iC9.GD2.CAR.IL-15 T cell product preparation, subjects will be assessed for initial study enrollment eligibility (prior to cell procurement) and then will have to meet criteria prior to starting lymphodepletion and prior to T cell infusion.\n\nInclusion Criteria for the Study:\n\n1. Written HIPAA authorization signed by legal guardian.\n2. Adequate performance status as defined by Lansky or Karnofsky performance status of ≥ 60 (Lansky for \\\u003C16 years of age).\n3. Life expectancy ≥12 weeks.\n4. Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. Bone marrow samples are acceptable as confirmation of neuroblastoma, confirmation of osteosarcoma at diagnosis\n5. High-risk neuroblastoma with persistent\u002Frefractory or relapsed disease, defined as:\n\n   1. First or greater relapse of neuroblastoma following completion of aggressive multi-drug frontline therapy.\n   2. First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy. Persistent\u002Frefractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).\n   3. Patients must be diagnosed with high risk neuroblastoma at initial diagnosis or if non-high risk at time of initial diagnosis must have had evidence of metastatic progression when \\>18 months of age as defined in the protocol or relapsed or refractory osteosarcoma that is not responsive to standard treatment.\n6. Measurable or evaluable disease per Revised INRC for subjects with neuroblastoma or measurable disease by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 criteria for subjects with osteosarcoma.\n7. Adequate central nervous system function as defined by:\n\n   1. No known Central Nervous System ( CNS) disease\n   2. No seizure disorder requiring antiepileptic drug therapy\n\nExclusion Criteria for the Study Subjects meeting any of the following exclusion criteria will not be able to participate in this study (procurement, lymphodepletion, and cell infusion).\n\n1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).\n2. Has a known additional malignancy that is active and\u002For progressive requiring treatment.\n3. History of hypersensitivity reactions to murine protein-containing products.\n4. History of hypersensitivity to cyclophosphamide or fludarabine.",[85,86,87],"CHILD","ADULT","OLDER_ADULT",[89,99],{"facility":90,"status":91,"city":92,"state":93,"zip":94,"country":95,"geoPoint":96},"Emory - Winship Cancer Institute","WITHDRAWN","Atlanta","Georgia","30322","United States",{"lat":97,"lon":98},33.749,-84.38798,{"facility":100,"status":8,"city":101,"state":102,"zip":103,"country":95,"contacts":104,"geoPoint":116},"Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill","Chapel Hill","North Carolina","27599-7295",[105,110,113],{"name":106,"role":107,"phone":108,"email":109},"Catherine Cheng","CONTACT","919-445-4208","UNCImmunotherapy@med.unc.edu",{"name":111,"role":107,"phone":112,"email":109},"Caroline Babinec","919-962-7426",{"name":114,"role":115},"George Hucks, MD","PRINCIPAL_INVESTIGATOR",{"lat":117,"lon":118},35.9132,-79.05584,[],[121],{"name":114,"affiliation":13,"role":115},[],[124],{"label":125,"url":126},"University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials","https:\u002F\u002Funclineberger.org\u002Fpatientcare\u002Fclinical-trials\u002F",{"nct_id":4,"conditions":128,"biomarkers":129},[19,20],[130],"Ganglioside GD2",{"nct_id":4,"found":15,"summary":132,"prompt_version":142},{"design":133,"status":134,"heading":135,"summary":136,"follow_up":137,"word_count":138,"commitments":139,"compensation":140,"drugs_mentioned":141},"This is an interventional study, meaning participants will receive a specific treatment. It plans to enroll 18 participants.","completed","Study of CAR T-Cells for Neuroblastoma or Osteosarcoma","This study is testing a new way to fight relapsed (returned) or refractory (not responding to treatment) neuroblastoma or osteosarcoma. It uses special immune cells called T-cells that are modified in the lab to better recognize and kill cancer cells. These modified cells, called iC9.GD2.CAR.IL-15 T-cells, are given after you receive two chemotherapy drugs, cyclophosphamide and fludarabine, to prepare your body. The main goal is to see how safe these T-cells are and what side effects they might cause in children and young adults. We are looking for 18 participants aged 18 months and older for this study.","Safety and side effects will be measured at 4 weeks after treatment.",98,"You will be assessed for eligibility before cell collection and again before starting treatment. You will receive cyclophosphamide and fludarabine before the T-cell infusion.","Not stated in the trial record.",[41,46,50],"v2"]