{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT04687761","title":"Clinical Trial to Assess the Safety and Tolerability of the Combination of Low-dose Cytarabine or Azacitidine Plus Venetoclax and Quizartinib in Newly Diagnosed AML Patients Aged Equal or More Than 60 Years Old","sponsor":"PETHEMA Foundation","phases":["PHASE1","PHASE2"],"status":"COMPLETED","indication":null,"disease":"leukemia, acute myeloid, susceptibility to"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of BCL2, CSF1R, FLT3, KIT has somatic-mutation evidence in leukemia, acute myeloid, susceptibility to","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: BCL2 in leukemia, acute myeloid, susceptibility to","url":"https://platform.opentargets.org/evidence/ENSG00000171791/MONDO_0100173","date":"2026-11-11T19:01:38.954Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"yes","detail":"FLT3: curated genetic literature","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: FLT3 in leukemia, acute myeloid, susceptibility to","url":"https://platform.opentargets.org/evidence/ENSG00000122025/MONDO_0100173","date":"2026-11-11T19:01:38.954Z"},"context":[{"figure":"2.6× relative probability of success, phase 1 to launch, with human genetic support","dataset":"Minikel et al., Nature 2024","years":"drug programs to 2023","caveat":"All therapy areas, mostly germline evidence; not a probability for this program."}]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"CSF1R, FLT3, KIT 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 NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761","date":"2026-11-11T19:01:38.954Z"},"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":"Azacitidine, Cytarabine: standard agents, not counted in these flags."},{"label":"BCL2 (via Venetoclax)","text":"Open Targets has no association between BCL2 and leukemia, acute myeloid, susceptibility to.","source":{"label":"Open Targets: BCL2 in leukemia, acute myeloid, susceptibility to","url":"https://platform.opentargets.org/evidence/ENSG00000171791/MONDO_0100173","date":"2026-11-11T19:01:38.954Z"}},{"label":"CSF1R (via Quizartinib)","text":"Open Targets has no association between CSF1R and leukemia, acute myeloid, susceptibility to.","source":{"label":"Open Targets: CSF1R in leukemia, acute myeloid, susceptibility to","url":"https://platform.opentargets.org/evidence/ENSG00000182578/MONDO_0100173","date":"2026-11-11T19:01:38.954Z"}},{"label":"FLT3 (via Quizartinib)","text":"Evidence types in leukemia, acute myeloid, susceptibility to: genetic_literature. Datasources: clingen.","source":{"label":"Open Targets: FLT3 in leukemia, acute myeloid, susceptibility to","url":"https://platform.opentargets.org/evidence/ENSG00000122025/MONDO_0100173","date":"2026-11-11T19:01:38.954Z"}},{"label":"KIT (via Quizartinib)","text":"Open Targets has no association between KIT and leukemia, acute myeloid, susceptibility to.","source":{"label":"Open Targets: KIT in leukemia, acute myeloid, susceptibility to","url":"https://platform.opentargets.org/evidence/ENSG00000157404/MONDO_0100173","date":"2026-11-11T19:01:38.954Z"}}],"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 NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761","date":"2026-11-11T19:01:38.954Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"113 enrolled; each patient moves a rate by 100 ÷ 113 = 0.9 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761","date":"2026-11-11T19:01:38.954Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Phase I: Recommended phase 2 dose (RP2D); Phase II: CR/Cri rate of AZA based and LDAC based","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761","date":"2026-11-11T19:01:38.954Z"},"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":"yes","detail":"Primary completion 2024-11-30, 23 months ago; no results posted","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761","date":"2026-11-11T19:01:38.954Z"},"context":[{"figure":"40.9% of applicable trials report results within a year","dataset":"Results-reporting studies summarised in spec §11","years":"all therapy areas","caveat":"All areas, not oncology only."}]}],"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":"147 terminated, withdrawn or suspended trials of drugs against BCL2; 9 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"BCL2: what already stopped","url":"/target/ENSG00000171791#stopped","date":"2026-11-11T19:01:38.983Z"}}],"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 15 sites in Spain","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761?tab=locations","date":"2026-11-11T19:01:38.954Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMA/PE/0000182075 (venetoclax, Treatment of malignant neoplasms of the haematopoietic and lymphoid tissue;Treatment of solid malignant tumours): PM: decision on the application for modification of an agreed PIP, 3 Jan 2025; EMEA-001821-PIP01-15-M08 (quizartinib, Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 14 Jun 2024","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/3/17/1954 withdrawn 12 Dec 2017: Treatment of mantle cell lymphoma; EU/3/16/1766 withdrawn 14 Oct 2016: Treatment of diffuse large B-cell lymphoma; EU/3/16/1617 withdrawn 17 Feb 2016: Treatment of acute myeloid leukaemia; EU/3/12/1080 withdrawn 6 Dec 2012: Treatment of chronic lymphocytic leukaemia; +1 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":"Vanflyta: authorised since 6 Nov 2023; Venclyxto: authorised since 4 Dec 2016; Vanflyta: refused","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 Venetoclax, Quizartinib","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":"2026-11-11T19:01:38.993Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"114 interventional studies of Venetoclax, Quizartinib include patients under 18; 87 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=%22Venetoclax%22+OR+%22Quizartinib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T19:01:39.003Z"},"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":"Cited case","text":"In February 2022 FDA asked its Oncologic Drugs Advisory Committee whether sintilimab's application, resting on ORIENT-11, a phase 3 run only in China, needed further trials showing it applies to US patients and US practice. One case, not a rule.","source":{"label":"FDA, ODAC 10 Feb 2022, draft questions","url":"https://www.fda.gov/media/156017/download","date":"2022-02-10"}},{"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":"PETHEMA Foundation (academic or other)","source":{"label":"ClinicalTrials.gov NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761","date":"2026-11-11T19:01:38.954Z"}},{"label":"principal investigator","text":"Pau Montesinos, MD, Hospital Universitario La Fe","source":{"label":"Person page","url":"/person/Pau%20Montesinos%2C%20MD","date":"2026-11-11T19:01:38.954Z"}},{"label":"principal investigator","text":"Juan Bergua, MD, Hospital San Pedro Alcántara","source":{"label":"Person page","url":"/person/Juan%20Bergua%2C%20MD","date":"2026-11-11T19:01:38.954Z"}},{"label":"study chair","text":"Carmen López-Carrero García, Fundación PETHEMA","source":{"label":"Person page","url":"/person/Carmen%20L%C3%B3pez-Carrero%20Garc%C3%ADa","date":"2026-11-11T19:01:38.954Z"}}],"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 NCT04687761","url":"https://clinicaltrials.gov/study/NCT04687761","date":"2026-11-11T19:01:38.954Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T19:01:38.954Z"},{"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":"2026-11-11T19:01:38.950Z"}