{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT04747236","title":"Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator's Choice in PTCL","sponsor":"University of Virginia","phases":["PHASE2"],"status":"RECRUITING","indication":null,"disease":"mature T-cell and NK-cell non-Hodgkin lymphoma"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of DNMT3A, DNMT1, HDAC1, HDAC3, HDAC6, DHFR has somatic-mutation evidence in mature T-cell and NK-cell non-Hodgkin lymphoma","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: DNMT3A in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000119772/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for DNMT3A, DNMT1, HDAC1, HDAC3, HDAC6, DHFR in mature T-cell and NK-cell non-Hodgkin lymphoma","rule":"Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence","source":{"label":"Open Targets: DNMT3A in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000119772/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"},"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":"no","detail":"Solid tumour","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236","date":"2026-11-11T17:23:57.806Z"},"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":"DNMT3A (via Azacytidine)","text":"Evidence types in mature T-cell and NK-cell non-Hodgkin lymphoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: DNMT3A in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000119772/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"}},{"label":"DNMT1 (via Azacytidine)","text":"Evidence types in mature T-cell and NK-cell non-Hodgkin lymphoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: DNMT1 in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000130816/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"}},{"label":"HDAC1 (via Romidepsin)","text":"Evidence types in mature T-cell and NK-cell non-Hodgkin lymphoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: HDAC1 in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000116478/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"}},{"label":"HDAC3 (via Romidepsin)","text":"Evidence types in mature T-cell and NK-cell non-Hodgkin lymphoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: HDAC3 in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000171720/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"}},{"label":"HDAC6 (via Romidepsin)","text":"Evidence types in mature T-cell and NK-cell non-Hodgkin lymphoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: HDAC6 in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000094631/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"}},{"label":"DHFR (via Pralatrexate)","text":"Evidence types in mature T-cell and NK-cell non-Hodgkin lymphoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: DHFR in mature T-cell and NK-cell non-Hodgkin lymphoma","url":"https://platform.opentargets.org/evidence/ENSG00000228716/MONDO_0000430","date":"2026-11-11T17:23:57.806Z"}}],"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 NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236","date":"2026-11-11T17:23:57.806Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"50 planned; each patient moves a rate by 100 ÷ 50 = 2.0 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236","date":"2026-11-11T17:23:57.806Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Progression free survival","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236","date":"2026-11-11T17:23:57.806Z"},"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":"Primary completion expected 2028-06-02; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236","date":"2026-11-11T17:23:57.806Z"},"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":"103 terminated, withdrawn or suspended trials of drugs against DNMT3A; 10 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"DNMT3A: what already stopped","url":"/target/ENSG00000119772#stopped","date":"2026-11-11T17:23:57.858Z"}}],"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":"yes","detail":"All 6 sites in United States","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236?tab=locations","date":"2026-11-11T17:23:57.806Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-001023-PIP01-10 (romidepsin, Treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated)): W: decision granting a waiver in all age groups for all conditions or indications, 3 Feb 2011; EMEA-000619-PIP02-10 (pralatrexate, Treatment of Hodgkin lymphoma;Treatment of lymphoblastic non-Hodgkin lymphoma;Treatment of mature B-cell non-Hodgkin lymphoma;Treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated)): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 2 Dec 2010","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/3/05/328 positive 28 Oct 2005: Treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated); EU/3/13/1151 positive 17 Jul 2013: Treatment of malignant thymoma; EU/3/12/1055 positive 10 Oct 2012: Treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated); EU/3/07/444 positive 13 Apr 2007: Treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated); +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":"no","detail":"Istodax: refused, orphan medicine; Folotyn: refused, orphan medicine","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 data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json","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 Azacytidine, Romidepsin, Belinostat, Pralatrexate","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":"2026-11-11T17:23:57.875Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"187 interventional studies of Azacytidine, Romidepsin, Belinostat, Pralatrexate include patients under 18; 69 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=%22Azacytidine%22+OR+%22Romidepsin%22+OR+%22Belinostat%22+OR+%22Pralatrexate%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T17:23:57.880Z"},"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":"University of Virginia (academic or other)","source":{"label":"ClinicalTrials.gov NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236","date":"2026-11-11T17:23:57.806Z"}},{"label":"principal investigator","text":"Craig Portell, MD, University of Virginia","source":{"label":"Person page","url":"/person/Craig%20Portell%2C%20MD","date":"2026-11-11T17:23:57.806Z"}}],"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 NCT04747236","url":"https://clinicaltrials.gov/study/NCT04747236","date":"2026-11-11T17:23:57.806Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T17:23:57.806Z"},{"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":"2026-11-11T17:23:57.801Z"}