{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT01886872","title":"Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia","sponsor":"National Cancer Institute (NCI)","phases":["PHASE3"],"status":"ACTIVE_NOT_RECRUITING","indication":null,"disease":null},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"not published","detail":"This trial's cancer could not be matched to an Open Targets disease.","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T19:10:23.295Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"not published","detail":"This trial's cancer could not be matched to an Open Targets disease.","rule":"Any germline or somatic human genetic evidence for the target in this cancer","source":{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T19:10:23.295Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"no","detail":"Not on the FDA list","rule":"Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study","source":{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"},"context":[]},{"id":"haematologic","label":"Haematologic cancer","value":"yes","detail":"Haematologic","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872","date":"2026-11-11T19:10:23.295Z"},"context":[{"figure":"Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid","dataset":"BIO / Informa / QLS 2021","years":"2011–2020","caveat":"Population-level, not a prediction."}]}],"facts":[{"label":"Background therapy","text":"Rituximab: standard agents, not counted in these flags."}],"pending":[{"what":"Normal-tissue expression in vital organs","source":"Human Protein Atlas (ticket 36)"},{"what":"Pan-essential in cell lines","source":"DepMap (ticket 36)"},{"what":"Approved drug on this target","source":"Drugs@FDA (ticket 30)"}]},{"n":2,"question":"Can the result be trusted?","flags":[{"id":"randomised","label":"Randomised","value":"yes","detail":"Randomised allocation","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872","date":"2026-11-11T19:10:23.295Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"547 enrolled; each patient moves a rate by 100 ÷ 547 = 0.2 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872","date":"2026-11-11T19:10:23.295Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Progression Free Survival (PFS)","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872","date":"2026-11-11T19:10:23.295Z"},"context":[{"figure":"Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3","dataset":"Otsuka 2021, 400 phase 3 oncology trials","years":"to 2020","caveat":"Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival."},{"figure":"52% of surrogate-to-OS correlations are low","dataset":"Prasad 2015","years":"published to 2014","caveat":"Shown with the figure above."}]},{"id":"results_overdue","label":"Results overdue","value":"no","detail":"Results posted 2019-12-30","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872?tab=results","date":"2026-11-11T19:10:23.295Z"},"context":[]}],"facts":[],"pending":[{"what":"Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff","source":"Readout extraction (ticket 32)"},{"what":"Primary endpoint changed between registry versions","source":"Registry versions in the store (ticket 32)"}]},{"n":3,"question":"What must it beat?","flags":[],"facts":[],"pending":[{"what":"Control-arm result and approved therapies for the same segment, with label links","source":"Drugs@FDA, FDA labels and readouts (tickets 30, 32)"}]},{"n":4,"question":"Too crowded, or too late?","flags":[],"facts":[{"label":"Stopped on this target","text":"102 terminated, withdrawn or suspended trials of drugs against BTK; 6 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"BTK: what already stopped","url":"/target/ENSG00000010671#stopped","date":"2026-11-11T19:10:23.321Z"}}],"pending":[{"what":"Programs on the target by phase and months behind the leader","source":"Programs and Drugs@FDA (ticket 33)"}]},{"n":5,"question":"Can it be approved, and stay approved?","flags":[{"id":"single_country","label":"Single-country","value":"no","detail":"937 sites in 2 countries; 917 in the United States (98%)","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872?tab=locations","date":"2026-11-11T19:10:23.295Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-001397-PIP04-17-M02 (Ibrutinib, Treatment of chronic Graft versus Host Disease (cGvHD)): PM: decision on the application for modification of an agreed PIP, 11 Aug 2023; EMEA-001397-PIP03-14-M06 (Ibrutinib, Treatment of mature B-cell neoplasms): PM: decision on the application for modification of an agreed PIP, 11 Aug 2021; compliance positive 25 Feb 2022; EMEA-001397-PIP06-17 (Ibrutinib, Treatment of lymphoplasmacytic lymphoma): W: decision granting a waiver in all age groups for all conditions or indications, 4 Oct 2017; EMEA-001397-PIP05-17 (Ibrutinib, Treatment of mantle cell lymphoma): W: decision granting a waiver in all age groups for all conditions or indications, 4 Oct 2017; +2 more","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-paediatric_investigation_plans-output-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/13/1212 withdrawn 16 Jan 2014: Treatment of follicular lymphoma; EU/3/13/1203 withdrawn 13 Nov 2013: Treatment of diffuse large B-cell lymphoma; EU/3/16/1780 withdrawn 18 Nov 2016: Treatment of graft-versus-host disease; EU/3/15/1541 withdrawn 10 Aug 2015: Treatment of marginal zone lymphoma; +3 more","rule":"An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-orphan_designations-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_authorised","label":"Authorised in the EU","value":"yes","detail":"Imbruvica: authorised since 21 Oct 2014","rule":"An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file","source":{"label":"EMA EPAR Imbruvica","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/imbruvica","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"fda_orphan","label":"FDA orphan designation","value":"not published","detail":"FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link","rule":"Would be: an FDA orphan designation names the drug","source":{"label":"FDA orphan designations search","url":"https://www.accessdata.fda.gov/scripts/opdlisting/oopd/","date":""},"context":[]},{"id":"fda_ped_approval","label":"FDA pediatric oncology approval","value":"no","detail":"FDA's table lists no pediatric approval of Bendamustine Hydrochloride, Ibrutinib","rule":"FDA's Pediatric Oncology Drug Approvals table names the drug","source":{"label":"FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03)","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology-drug-approvals","date":"2026-11-11T19:10:23.332Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"32 interventional studies of Bendamustine Hydrochloride, Ibrutinib include patients under 18; 10 are recruiting, not yet recruiting or active","rule":"The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age","source":{"label":"ClinicalTrials.gov search","url":"https://clinicaltrials.gov/search?intr=%22Bendamustine+Hydrochloride%22+OR+%22Ibrutinib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T19:10:23.336Z"},"context":[]}],"facts":[{"label":"Caveat","text":"Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality."},{"label":"Rare pediatric disease voucher","text":"FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news.","source":{"label":"FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs","url":"https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs","date":"2026-11-11"}}],"pending":[{"what":"Precedent approvals for target, modality and endpoint; accelerated-approval status","source":"Drugs@FDA and FDA accelerated-approval tables (ticket 30)"}]},{"n":6,"question":"Can the sponsor finish?","flags":[],"facts":[{"label":"Sponsor","text":"National Cancer Institute (NCI) (academic or other)","source":{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872","date":"2026-11-11T19:10:23.295Z"}},{"label":"principal investigator","text":"Jennifer A Woyach, Alliance for Clinical Trials in Oncology","source":{"label":"Person page","url":"/person/Jennifer%20A%20Woyach","date":"2026-11-11T19:10:23.295Z"}}],"pending":[{"what":"Filed cash, quarterly spend and the runway arithmetic","source":"SEC XBRL company facts (ticket 37)"},{"what":"Sponsor's completed vs stopped oncology trials and results-reporting record","source":"Registry, by company (ticket 37)"}]}],"limits":"Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.","sources":[{"label":"ClinicalTrials.gov NCT01886872","url":"https://clinicaltrials.gov/study/NCT01886872","date":"2026-11-11T19:10:23.295Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T19:10:23.295Z"},{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"}]},"source":"ClinicalTrials.gov + Open Targets","fetchedAt":"2026-11-11T19:10:23.284Z"}