{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT03117751","title":"Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma","sponsor":"St. Jude Children's Research Hospital","phases":["PHASE2","PHASE3"],"status":"ACTIVE_NOT_RECRUITING","indication":{"slug":"pediatric-all","name":"Childhood acute lymphoblastic leukemia"},"disease":"childhood acute lymphoblastic leukemia"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of PPAT, ABL1, BCR has somatic-mutation evidence in childhood acute lymphoblastic leukemia","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: PPAT in childhood acute lymphoblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000128059/MONDO_0000870","date":"2026-11-11T16:19:48.779Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for PPAT, ABL1, BCR in childhood acute lymphoblastic leukemia","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: PPAT in childhood acute lymphoblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000128059/MONDO_0000870","date":"2026-11-11T16:19:48.779Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"ABL1 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 NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751","date":"2026-11-11T16:19:48.779Z"},"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":"Vincristine, Daunorubicin, Cyclophosphamide, Cytarabine, Methotrexate, Bortezomib, Doxorubicin, Etoposide, Idarubicin: standard agents, not counted in these flags."},{"label":"PPAT (via Mercaptopurine)","text":"Open Targets has no association between PPAT and childhood acute lymphoblastic leukemia.","source":{"label":"Open Targets: PPAT in childhood acute lymphoblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000128059/MONDO_0000870","date":"2026-11-11T16:19:48.779Z"}},{"label":"ABL1 (via Dasatinib)","text":"Open Targets has no association between ABL1 and childhood acute lymphoblastic leukemia.","source":{"label":"Open Targets: ABL1 in childhood acute lymphoblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000097007/MONDO_0000870","date":"2026-11-11T16:19:48.779Z"}},{"label":"BCR (via Dasatinib)","text":"Open Targets has no association between BCR and childhood acute lymphoblastic leukemia.","source":{"label":"Open Targets: BCR in childhood acute lymphoblastic leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000186716/MONDO_0000870","date":"2026-11-11T16:19:48.779Z"}}],"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 NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751","date":"2026-11-11T16:19:48.779Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"790 enrolled; each patient moves a rate by 100 ÷ 790 = 0.1 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751","date":"2026-11-11T16:19:48.779Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Event-free survival of ALL patients (EFS); Proportion of patients with CEP72TT genotype who develop two or more episodes of Grade 2 or higher neuropathy during …; Cumulative incidence of Grade 2 or higher neuropathy in patients with CEP72 CC or CT genotype","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751","date":"2026-11-11T16:19:48.779Z"},"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 2026-09-30; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751","date":"2026-11-11T16:19:48.779Z"},"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":"69 terminated, withdrawn or suspended trials of drugs against PPAT; 7 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"PPAT: what already stopped","url":"/target/ENSG00000128059#stopped","date":"2026-11-11T16:19:48.789Z"}}],"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":"8 sites in 2 countries; 7 in the United States (88%)","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751?tab=locations","date":"2026-11-11T16:19:48.779Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-000567-PIP01-09-M05 (dasatinib, Treatment of Philadelphia-chromosome (BCR-ABL translocation)-positive acute lymphoblastic leukaemia;Treatment of Philadelphia-chromosome (BCR-ABL translocation)-positive chronic myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 16 Feb 2018; compliance positive 23 Feb 2018","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA EMEA-000567-PIP01-09-M05","url":"https://www.ema.europa.eu/en/medicines/human/paediatric-investigation-plans/emea-000567-pip01-09-m05","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/26/3246 positive 22 Jun 2026: Treatment of Diamond-Blackfan anaemia; EU/3/09/628 expired 30 Apr 2009: Treatment of acute lymphoblastic leukaemia; EU/3/05/338 expired 23 Dec 2005: Treatment of acute lymphoblastic leukaemia; EU/3/05/339 expired 23 Dec 2005: Treatment of chronic myeloid 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":"Sprycel: authorised since 20 Nov 2006; Oncaspar: authorised since 14 Jan 2016; Dasatinib Accord Healthcare: authorised since 26 Jul 2024; Xaluprine (previously Mercaptopurine Nova Laboratories): authorised since 9 Mar 2012; +3 more","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":"yes","detail":"Pegaspargase [Oncaspar], 24 Jul 2006: As a component of a multi-agent chemotherapeutic regimen for the first-line treatment of pediatric and adult patients with acute lymphoblastic leukemia (ALL); Pegaspargase [Oncaspar], 1 Feb 1994: As a component of a multi-agent chemotherapeutic regimen for the treatment of pediatric and adult patients with ALL and hypersensitivity to native forms of L-asparaginase; Mercaptopurine [Purinethol tablet] &, 11 Sept 1953: Treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen; +2 more","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":"2026-11-11T16:19:48.799Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"313 interventional studies of Pegaspargase, Erwinase®, Mercaptopurine, Dasatinib include patients under 18; 62 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=%22Pegaspargase%22+OR+%22Erwinase%C2%AE%22+OR+%22Mercaptopurine%22+OR+%22Dasatinib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T16:19:48.800Z"},"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":"St. Jude Children's Research Hospital (academic or other)","source":{"label":"ClinicalTrials.gov NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751","date":"2026-11-11T16:19:48.779Z"}},{"label":"principal investigator","text":"Hiroto Inaba, MD, PhD, St. Jude Children's Research Hospital","source":{"label":"Person page","url":"/person/Hiroto%20Inaba%2C%20MD%2C%20PhD?ind=pediatric-all","date":"2026-11-11T16:19:48.779Z"}}],"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 NCT03117751","url":"https://clinicaltrials.gov/study/NCT03117751","date":"2026-11-11T16:19:48.779Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T16:19:48.779Z"},{"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":"2026-11-11T16:19:48.778Z"}