{"entity":{"id":"belinda","kind":"trial","name":"BELINDA","aka":[],"tldr":"The one second-line CAR-T trial that failed, a reminder that manufacturing time and trial design can erase a real effect.","summary":"BELINDA, trial NCT03570892 sponsored by Novartis and reported in 2021, was the one second-line CAR-T trial that failed, a reminder that manufacturing time and trial design can erase a real effect. It randomised 322 patients with early-relapsed or refractory aggressive B-cell lymphoma to tisagenlecleucel or salvage chemotherapy and transplant and found no difference in event-free survival, which the record attributes to a long vein-to-vein time of 52 days, permitted crossover chemotherapy before CAR-T and a strict week-twelve event definition. OnCo links it to lymphoma, CAR-T, the pairing of CAR-T before transplant at early relapse and the JULIET, TRANSFORM and ZUMA-7 papers, and it is contradicted by ZUMA-7 and TRANSFORM, which used faster products and no crossover. Whether tisagenlecleucel would have matched them under the same design is the question the trial cannot answer.","status":"negative","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03570892","url":"https://clinicaltrials.gov/study/NCT03570892"}],"tags":["lesson:trial-design"],"related":["lymphoma-roadmap","juliet","transcend-nhl-001","lymphoma-ev-manufacturing-time-as-a-trial-endpoint"],"cancers":["dlbcl"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-belinda-tisagenlecleucel-second-line-nejm-2022"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03570892","phase":"3","setting":"Early-relapsed/refractory aggressive B-cell lymphoma: tisagenlecleucel vs salvage + transplant","sponsor":"Novartis","result":"EFS HR 1.07 (negative).","started":"2019-05-09","startedType":"actual","yearReported":2021,"enrolled":330,"enrolledBasis":"registry","outcomes":[{"endpoint":"Event-free survival (median)","primary":true,"unit":"months","arms":[{"name":"Tisagenlecleucel","n":162,"value":3},{"name":"Standard care","n":160,"value":3}],"hr":1.07,"ci":[0.82,1.4],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2116596"}],"replication":"Contradicted by ZUMA-7 and TRANSFORM, which used faster products and no crossover before CAR-T."},"route":"/trials/belinda/","neighbours":{"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"trial":[{"id":"juliet","kind":"trial","name":"JULIET","route":"/trials/juliet/"},{"id":"transcend-nhl-001","kind":"trial","name":"TRANSCEND NHL 001","route":"/trials/transcend-nhl-001/"},{"id":"transform","kind":"trial","name":"TRANSFORM","route":"/trials/transform/"},{"id":"zuma-7","kind":"trial","name":"ZUMA-7","route":"/trials/zuma-7/"}],"idea":[{"id":"lymphoma-ev-manufacturing-time-as-a-trial-endpoint","kind":"idea","name":"Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote","route":"/ideas/lymphoma-ev-manufacturing-time-as-a-trial-endpoint/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"paper":[{"id":"paper-juliet-tisagenlecleucel-dlbcl-nejm-2019","kind":"paper","name":"JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma","route":"/key-papers/paper-juliet-tisagenlecleucel-dlbcl-nejm-2019/"},{"id":"paper-belinda-tisagenlecleucel-second-line-nejm-2022","kind":"paper","name":"Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma","route":"/key-papers/paper-belinda-tisagenlecleucel-second-line-nejm-2022/"},{"id":"paper-transform-liso-cel-lancet-2022","kind":"paper","name":"TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma","route":"/key-papers/paper-transform-liso-cel-lancet-2022/"},{"id":"paper-zuma-7-axi-cel-second-line-nejm-2022","kind":"paper","name":"ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early","route":"/key-papers/paper-zuma-7-axi-cel-second-line-nejm-2022/"}],"pairing":[{"id":"car-t-before-transplant-lbcl","kind":"pairing","name":"Early relapse: CAR-T before transplant","route":"/pairings/car-t-before-transplant-lbcl/"}],"term":[{"id":"lymphoma-tx-failed-and-negative","kind":"term","name":"Lymphoma treatments that did not work: the negative trials worth knowing","route":"/terms/lymphoma-tx-failed-and-negative/"},{"id":"lymphoma-tx-car-t-pathway","kind":"term","name":"The CAR-T pathway in lymphoma: referral, apheresis, bridging and the waiting","route":"/terms/lymphoma-tx-car-t-pathway/"},{"id":"lymphoma-decision-transplant-or-car-t","kind":"term","name":"Transplant or CAR-T at second line in diffuse large B-cell lymphoma","route":"/terms/lymphoma-decision-transplant-or-car-t/"},{"id":"trial-protocol","kind":"term","name":"Trial protocol and statistical analysis plan","route":"/terms/trial-protocol/"},{"id":"trial-failure-modes","kind":"term","name":"Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover","route":"/terms/trial-failure-modes/"}]}}