{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT05645718","title":"Study of Pedi-cRIB: Mini-Hyper-CVD With Condensed Rituximab, Inotuzumab Ozogamicin and Blinatumomab (cRIB) for Relapsed Therapy for Pediatric With B-Cell Lineage Acute Lymphocytic Leukemia","sponsor":"M.D. Anderson Cancer Center","phases":["PHASE2"],"status":"RECRUITING","indication":null,"disease":"leukemia"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of CD3E, CD3G, CD3D, PPAT, CD22 has somatic-mutation evidence in leukemia","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: CD3E in leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000198851/MONDO_0005059","date":"2026-11-11T22:10:26.482Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for CD3E, CD3G, CD3D, PPAT, CD22 in 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: CD3E in leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000198851/MONDO_0005059","date":"2026-11-11T22:10:26.482Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"CD22 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 NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718","date":"2026-11-11T22:10:26.482Z"},"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":"Cyclophosphamide, Vincristine, Methotrexate, Cytarabine, Pegfilgrastim, Rituximab: standard agents, not counted in these flags."},{"label":"CD3E (via Blinatumomab)","text":"Evidence types in leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: CD3E in leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000198851/MONDO_0005059","date":"2026-11-11T22:10:26.482Z"}},{"label":"CD3G (via Blinatumomab)","text":"Evidence types in leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: CD3G in leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000160654/MONDO_0005059","date":"2026-11-11T22:10:26.482Z"}},{"label":"CD3D (via Blinatumomab)","text":"Evidence types in leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: CD3D in leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000167286/MONDO_0005059","date":"2026-11-11T22:10:26.482Z"}},{"label":"PPAT (via Mercaptopurine)","text":"Evidence types in leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: PPAT in leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000128059/MONDO_0005059","date":"2026-11-11T22:10:26.482Z"}},{"label":"CD22 (via Inotuzumab ozogamicin)","text":"Evidence types in leukemia: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: CD22 in leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000012124/MONDO_0005059","date":"2026-11-11T22:10:26.482Z"}}],"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":"no","detail":"Non-randomised","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718","date":"2026-11-11T22:10:26.482Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"yes","detail":"27 planned; each patient moves a rate by 100 ÷ 27 = 3.7 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718","date":"2026-11-11T22:10:26.482Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Ev…","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718","date":"2026-11-11T22:10:26.482Z"},"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 2027-12-31; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718","date":"2026-11-11T22:10:26.482Z"},"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":"87 terminated, withdrawn or suspended trials of drugs against CD3E; 9 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"CD3E: what already stopped","url":"/target/ENSG00000198851#stopped","date":"2026-11-11T22:10:26.493Z"}}],"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":"The only site is in United States","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718?tab=locations","date":"2026-11-11T22:10:26.482Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMA/PE/0000221213 (blinatumomab, Treatment of B-lymphoblastic leukaemia/lymphoma): PM: decision on the application for modification of an agreed PIP, 3 Jan 2025; EMEA-000574-PIP02-12-M04 (blinatumomab, Treatment of acute lymphoblastic leukaemia): PM: decision on the application for modification of an agreed PIP, 27 Oct 2023; compliance positive 23 Feb 2024; EMEA-001429-PIP01-13-M07 (Inotuzumab ozogamicin, Treatment of B cell acute lymphoblastic leukaemia): PM: decision on the application for modification of an agreed PIP, 10 Mar 2023","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/3/09/628 expired 30 Apr 2009: Treatment of acute lymphoblastic leukaemia; EU/3/03/176 withdrawn 1 Dec 2003: Treatment of chronic lymphocytic leukaemia; EU/3/03/175 withdrawn 1 Dec 2003: Treatment of mantle cell lymphoma; EU/3/09/650 positive 24 Jul 2009: Treatment of acute lymphoblastic leukaemia; +2 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":"Blincyto: authorised since 23 Nov 2015, orphan medicine; Besponsa: authorised since 28 Jun 2017, orphan medicine; Xaluprine (previously Mercaptopurine Nova Laboratories): authorised since 9 Mar 2012; Loulla: application withdrawn, 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":"yes","detail":"Blinatumomab [Blincyto], 14 Jun 2024: Treatment of CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL) in the consolidation phase of multiphase chemotherapy in adult and pediatric patients one month and older; Blinatumomab [Blincyto], 29 Mar 2018: Treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adult and pediatric patients one month and older; Blinatumomab [Blincyto], 11 Jul 2017: Treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older; +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":"2026-11-11T22:10:26.502Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"271 interventional studies of Blinatumomab, Mercaptopurine, Inotuzumab ozogamicin 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=%22Blinatumomab%22+OR+%22Mercaptopurine%22+OR+%22Inotuzumab+ozogamicin%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T22:10:26.507Z"},"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":"M.D. Anderson Cancer Center (academic or other)","source":{"label":"ClinicalTrials.gov NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718","date":"2026-11-11T22:10:26.482Z"}},{"label":"principal investigator","text":"David McCall, MD, M.D. Anderson Cancer Center","source":{"label":"Person page","url":"/person/David%20McCall%2C%20MD","date":"2026-11-11T22:10:26.482Z"}}],"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 NCT05645718","url":"https://clinicaltrials.gov/study/NCT05645718","date":"2026-11-11T22:10:26.482Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T22:10:26.482Z"},{"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":"2026-11-11T22:10:26.479Z"}