[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100463123":3},{"organization":4,"armGroups":7,"interventions":18,"overallOfficials":11,"centralContacts":28,"locations":38,"responsibleParty":176,"collaborators":11,"id":178,"slug":179,"hasResults":180,"nctId":181,"briefTitle":182,"officialTitle":182,"acronym":183,"eligibilityCriteria":184,"healthyVolunteers":180,"sex":185,"minAge":186,"maxAge":187,"enrollmentInfo":188,"targetDuration":11,"studyType":191,"phases":192,"briefSummary":195,"conditions":196,"keywords":11,"overallStatus":41,"whyStopped":11,"lastUpdateSubmitDate":199,"lastUpdatePostDateStruct":200,"startDateStruct":203,"completionDateStruct":205,"leadSponsor":207,"locationsCount":208},{"fullName":5,"class":6},"Assistance Publique - Hôpitaux de Paris","OTHER",[8,14],{"label":9,"type":10,"description":11,"interventionNames":12},"Patients with MRD negative disease status: Time to Event Continual Reassessment Method (TITE-CRM)","EXPERIMENTAL",null,[13],"Drug: Decreasing starting times for beginning nivolumab (Time to Event Continual Reassessment Method (TITE-CRM) )",{"label":15,"type":10,"description":11,"interventionNames":16},"For relapsed patients",[17],"Drug: Nivolumab starting at day -1",[19,24],{"type":20,"name":21,"description":22,"armGroupLabels":23,"otherNames":11},"DRUG","Decreasing starting times for beginning nivolumab (Time to Event Continual Reassessment Method (TITE-CRM) )","Patients included first receive a lympho-depleting chemotherapy by Fludarabine \u002F Cyclophosphamide. tisagenlecleucel infusion should then be administered 2 to 14 days after completion of chemotherapy.\n\nNivolumab (Opdivo®) will be given intravenously at 3mg\u002Fkg every 2 weeks. It will include patients with MRD negative disease status.\n\n1. Four decreasing starting times for beginning nivolumab (day 14, day 11, day 5 and day -1) will be available for testing\n2. Patients will be enrolled sequentially by cohorts of 3 with escalation between cohorts based only on the limiting toxicities between infusion and D28\n\nNivolumab will be given until 12 months after tisagenlecleucel infusion in case of response.",[9],{"type":20,"name":25,"description":26,"armGroupLabels":27,"otherNames":11},"Nivolumab starting at day -1","It will include relapsed patients. Patients included first receive a lympho-depleting chemotherapy by Fludarabine \u002F Cyclophosphamide. tisagenlecleucel infusion should then be administered 2 to 14 days after completion of chemotherapy.\n\nNivolumab (Opdivo®) will be given intravenously at 3mg\u002Fkg every 2 weeks.\n\n-nivolumab starting at day -1.\n\nNivolumab will be given until 12 months after tisagenlecleucel infusion in case of response.",[15],[29,34],{"name":30,"role":31,"phone":32,"phoneExt":11,"email":33},"Andre Baruchel, Pr","CONTACT","+331 40 03 53 88","andre.baruchel@aphp.fr",{"name":35,"role":31,"phone":36,"phoneExt":11,"email":37},"Jérôme Lambert, Pr","+33142499742","jerome.lambert@u-paris.fr",[39,54,65,76,84,91,102,113,124,135,146,154,165],{"facility":40,"status":41,"city":42,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":45,"geoPoint":50,"contacts":51},"CHRU Bordeaux","RECRUITING","Bordeaux","France","FR",{"type":46,"coordinates":47},"Point",[48,49],-0.58046,44.84124,{"lat":49,"lon":48},[52],{"name":53,"role":31,"phone":11,"phoneExt":11,"email":11},"Marie Angoso",{"facility":55,"status":41,"city":56,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":57,"geoPoint":61,"contacts":62},"CHRU Lille","Lille",{"type":46,"coordinates":58},[59,60],3.05512,50.63391,{"lat":60,"lon":59},[63],{"name":64,"role":31,"phone":11,"phoneExt":11,"email":11},"Brigitte Nelken",{"facility":66,"status":41,"city":67,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":68,"geoPoint":72,"contacts":73},"HCL - Lyon Sud","Lyon",{"type":46,"coordinates":69},[70,71],4.84789,45.74906,{"lat":71,"lon":70},[74],{"name":75,"role":31,"phone":11,"phoneExt":11,"email":11},"Marie Balsat",{"facility":77,"status":41,"city":67,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":78,"geoPoint":80,"contacts":81},"HCL",{"type":46,"coordinates":79},[70,71],{"lat":71,"lon":70},[82],{"name":83,"role":31,"phone":11,"phoneExt":11,"email":11},"Carine Halfan Domenech",{"facility":77,"status":41,"city":67,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":85,"geoPoint":87,"contacts":88},{"type":46,"coordinates":86},[70,71],{"lat":71,"lon":70},[89],{"name":90,"role":31,"phone":11,"phoneExt":11,"email":11},"Solene Remy",{"facility":92,"status":41,"city":93,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":94,"geoPoint":98,"contacts":99},"Hôpital pour enfants - La Timone","Marseille",{"type":46,"coordinates":95},[96,97],5.38107,43.29695,{"lat":97,"lon":96},[100],{"name":101,"role":31,"phone":11,"phoneExt":11,"email":11},"Michel Gerard",{"facility":103,"status":41,"city":104,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":105,"geoPoint":109,"contacts":110},"CHU Montpellier - Hopital Arnaud de Villeneuve","Montpellier",{"type":46,"coordinates":106},[107,108],3.87635,43.61093,{"lat":108,"lon":107},[111],{"name":112,"role":31,"phone":11,"phoneExt":11,"email":11},"Anne Sirvent",{"facility":114,"status":41,"city":115,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":116,"geoPoint":120,"contacts":121},"CHU Nancy","Nancy",{"type":46,"coordinates":117},[118,119],6.18496,48.68439,{"lat":119,"lon":118},[122],{"name":123,"role":31,"phone":11,"phoneExt":11,"email":11},"Cécile Pochon",{"facility":125,"status":41,"city":126,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":127,"geoPoint":131,"contacts":132},"CHU Nantes - Hopital Mère-enfants","Nantes",{"type":46,"coordinates":128},[129,130],-1.55336,47.21725,{"lat":130,"lon":129},[133],{"name":134,"role":31,"phone":11,"phoneExt":11,"email":11},"Fanny Rialland",{"facility":136,"status":41,"city":137,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":138,"geoPoint":142,"contacts":143},"Robert Debre hospital","Paris",{"type":46,"coordinates":139},[140,141],2.3488,48.85341,{"lat":141,"lon":140},[144],{"name":145,"role":31,"phone":11,"phoneExt":11,"email":11},"André Baruchel",{"facility":147,"status":41,"city":137,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":148,"geoPoint":150,"contacts":151},"Saint Louis hospital",{"type":46,"coordinates":149},[140,141],{"lat":141,"lon":140},[152],{"name":153,"role":31,"phone":11,"phoneExt":11,"email":11},"Nicolas Boissel",{"facility":155,"status":41,"city":156,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":157,"geoPoint":161,"contacts":162},"CHU Rouen","Rouen",{"type":46,"coordinates":158},[159,160],1.09932,49.44313,{"lat":160,"lon":159},[163],{"name":164,"role":31,"phone":11,"phoneExt":11,"email":11},"Nimrod Buchbinder",{"facility":166,"status":41,"city":167,"state":11,"zip":11,"country":43,"countryCode":44,"cosmosGeoPoint":168,"geoPoint":172,"contacts":173},"CHRU Strasbourg","Strasbourg",{"type":46,"coordinates":169},[170,171],7.74553,48.58392,{"lat":171,"lon":170},[174],{"name":175,"role":31,"phone":11,"phoneExt":11,"email":11},"Catherine Paillard",{"type":177,"investigatorFullName":11,"investigatorTitle":11,"investigatorAffiliation":11,"oldNameTitle":11,"oldOrganization":11},"SPONSOR","100463123","phase-1-combination-of-an-anti-pd1-antibody-with-tisagenlecleucel-reinfusion-in-children-adolescents-and-young-adults-with-acute-lymphoblastic-leukemia-after-loss-of-persistence-100463123",false,"NCT05310591","Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence","CAPTiRALL","Inclusion Criteria:\n\n* Patients aged from 1 to 25 years (pediatric and young adults) with a history of CD19+ relapsed or refractory B-ALL (any relapse after HSCT, 2nd relapse or later, refractory ALL).\n* Patient must have a second tisagenlecleucel (Kymriah ®) product available\n* Cohort 1: previously treated by tisagenlecleucel (Kymriah ®), and who present an early loss of B-cell aplasia defined by blood B lymphocytes \\\u003C 10 \u002Fmm3 and\u002F or \\\u003C 3% of total lymphocytes (\\\u003C 6 months after infusion) while still being in CR with undetectable MRD\n* Cohort 2: previously treated by tisagenlecleucel (Kymriah ®), who present a loss of B-cell aplasia defined by blood B lymphocytes \\\u003C 10 \u002Fmm3 and\u002F or \\\u003C 3% of total lymphocytes and a CD19+ ALL detectable disease in the marrow and\u002For Blood\n* Life expectancy \\> 12 weeks.\n* Karnofsky (age \\> 16) Lansky (age \\\u003C 16) \\> 70 at screening.\n* No organ dysfunction\n* Who have signed an informed consent\n* Affiliation to social security or any health insurance (as a beneficiary or assignee)\n\nExclusion Criteria:\n\n* Patient has received intervening therapy for leukemia after first tisagenlecleucel infusion (chemotherapy, anti leukemic immunotherapy, ITK, allogeneic HSCT).\n* Patient has an active autoimmune disease requiring systemic treatment within the past 2 years.\n* Patient has known history of, or any evidence of active, non-infectious pneumonitis.\n* Patient has a history of non-infectious pneumonitis that required steroid or has current pneumonitis.\n* Had receive prior therapy with an anti-PD1, Anti- PDL1 or anti-PDL2 agent.\n* Patient has hypersensivity to pembrolizumab\u002F nivolumab or one of its excipients\n* Patient has received a live vaccine injection within 45 days of planned start of study therapy.\n* Patients with concomitant genetic syndromes associated with bone marrow failure states: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down syndrome will not be excluded.\n* Patients with Burkitt's lymphoma\u002Fleukemia\n* Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.\n* Prior treatment with any gene therapy product except first tisagenlecleucel (Kymriah ®) injection.\n* Prior treatment with any anti-CD19\u002Fanti-CD3 therapy, or any other anti-CD19 therapy, except for patients pre-treated with blinatumomab and\u002For tisagenlecleucel (Kymriah®)\n* Prior anti-cancer monoclonal antibody within 4 weeks before starting the study.\n* Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent.\n* Active or latent hepatitis B or active hepatitis C (test within 8 weeks of Screening), or any uncontrolled infection at Screening.\n* Human immunodeficiency virus (HIV) positive test within 8 weeks of Screening.\n* Presence of grade 2 to 4 acute or extensive chronic GVHD.\n* Active CNS involvement by malignancy, defined as CNS-3 per NCCN guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible.\n* Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening.\n* Previous or concurrent malignancy with the following exceptions:\n\n  * Adequately treated basal cell or squamous cell carcinoma\n  * in situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study.\n  * A primary malignancy completely resected and in CR for ≥ 5 years\n* Pregnant or lactating women (female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion)\n* Patient with hypersensivity to Fludarabine and\u002For cyclophosphamide and\u002For tisagenlecleucel and\u002For nivolumab or one of their excipients.","ALL","1 Year","25 Years",{"count":189,"type":190},26,"ESTIMATED","INTERVENTIONAL",[193,194],"PHASE1","PHASE2","Tisagenlecleucel (CTL019) is an anti-CD19 autologous Chimeric Antigen Receptor (CAR) T-cell therapy, which has shown dramatic early results in advanced ALLs. Early loss of B-cell aplasia (recovery of B-cells in marrow\u002F peripheral blood within 6 months after infusion), a marker of the loss or non-functionality of the CAR T-cells, is associated to a very high risk of relapse. A reinfusion of CTL019, even after Fludarabine-Cyclophosphamide reconditioning, frequently fails to induce further expansion as observed in UPENN studies and in the Robert Debré Hospital experience.\n\nNon-persistence of CAR T-cells may be due to immune- mediated rejection or environment-mediated suppression of their growth. Evidence for increased PD-1 expression in CAR T-cells between infusion and peak expansion has been demonstrated in clinical samples.\n\nPreclinical data and few clinical data support a role of PD- 1-PD-L1 blockade in improving the effectiveness of CAR T-cell therapy.\n\nThe objectives of this phase I\u002FII study is to determine the safety, efficacy and feasibility of Nivolumab (Opdivo®)- an anti-PD1 treatment- combined to tisagenlecleucel in a cohort of relapsed or refractory B-ALL patients, aged 1-25 years old, previously treated by tisagenlecleucel (Kymriah®), with a demonstrated early loss of B-cell aplasia (within 6 months), a surrogate marker of the loss of CAR T-cells or their non- functionality.\n\nMore specifically, the main objectives are:\n\n• In cohort 1 that includes patients with a MRD negative disease status combined to an early loss (within 6 months) of B-cell aplasia :\n\nTo determine the optimal starting time of Nivolumab (Opdivo®) in terms of safety and efficacy among 4 candidate time points (day 14, day 11, day 5, and day - 1).\n\n• In cohort 2 that includes relapsed patients with an early loss (within 6 months) of B-cell aplasia :\n\nTo estimate the feasibility in terms of safety and efficacy of a very early start of nivolumab (day-1), prior to the reinfusion of tisagenlecleucel",[197,198],"B Acute Lymphoblastic Leukemia","Acute Lymphoblastic Leukemia, in Relapse","2024-05-26",{"date":201,"type":202},"2024-05-29","ACTUAL",{"date":204,"type":202},"2023-03-15",{"date":206,"type":190},"2027-03",{"name":5,"class":6},13]