{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT07582172","title":"Total Marrow and Lymphoid Irradiation in Combination With Fludarabine and Melphalan as Conditioning for Allogeneic Peripheral Blood Stem Cell Hematopoietic Cell Transplant in Older Patients With Refractory and Relapsed Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome","sponsor":"City of Hope Medical Center","phases":["PHASE2"],"status":"RECRUITING","indication":{"slug":"aml","name":"Acute myeloid leukemia"},"disease":"acute myeloid leukemia"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"yes","detail":"FGFR2 in acute myeloid leukemia","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: FGFR2 in acute myeloid leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000066468/MONDO_0018874","date":"2026-11-11T18:13:07.736Z"},"context":[{"figure":"2.3× relative success for targets with somatic (IntOGen) support in oncology","dataset":"Minikel et al., Nature 2024","years":"drug programs to 2023","caveat":"A ratio between groups, not a probability for this program; mostly phase 2 to 3."}]},{"id":"human_genetic","label":"Human genetic evidence","value":"yes","detail":"FGFR2: somatic","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: FGFR2 in acute myeloid leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000066468/MONDO_0018874","date":"2026-11-11T18:13:07.736Z"},"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":"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 NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172","date":"2026-11-11T18:13:07.736Z"},"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":"RRM1 (via Fludarabine Phosphate)","text":"Evidence types in acute myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: RRM1 in acute myeloid leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000167325/MONDO_0018874","date":"2026-11-11T18:13:07.736Z"}},{"label":"RRM2B (via Fludarabine Phosphate)","text":"Evidence types in acute myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: RRM2B in acute myeloid leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000048392/MONDO_0018874","date":"2026-11-11T18:13:07.736Z"}},{"label":"RRM2 (via Fludarabine Phosphate)","text":"Evidence types in acute myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: RRM2 in acute myeloid leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000171848/MONDO_0018874","date":"2026-11-11T18:13:07.736Z"}},{"label":"FGFR2 (via Palifermin)","text":"Evidence types in acute myeloid leukemia: literature, somatic_mutation, clinical; literature listed separately from human genetics. Datasources: cancer_gene_census, clinical_precedence, europepmc.","source":{"label":"Open Targets: FGFR2 in acute myeloid leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000066468/MONDO_0018874","date":"2026-11-11T18:13:07.736Z"}},{"label":"FKBP1A (via Sirolimus)","text":"Evidence types in acute myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: FKBP1A in acute myeloid leukemia","url":"https://platform.opentargets.org/evidence/ENSG00000088832/MONDO_0018874","date":"2026-11-11T18:13:07.736Z"}}],"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":"Single group","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172","date":"2026-11-11T18:13:07.736Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"35 planned; each patient moves a rate by 100 ÷ 35 = 2.9 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172","date":"2026-11-11T18:13:07.736Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Leukemia-free survival","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172","date":"2026-11-11T18:13:07.736Z"},"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 2031-11-05; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172","date":"2026-11-11T18:13:07.736Z"},"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":"1131 terminated, withdrawn or suspended trials of drugs against RRM1; 6 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"RRM1: what already stopped","url":"/target/ENSG00000167325#stopped","date":"2026-11-11T18:13:07.790Z"}}],"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 NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172?tab=locations","date":"2026-11-11T18:13:07.736Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-003168-PIP01-21 (sirolimus, Treatment of tuberous sclerosis complex): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 2 Dec 2022; EMEA-003168-PIP01-21 (sirolimus, Treatment of tuberous sclerosis complex): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 2 Dec 2022; EMEA-002982-PIP01-21 (sirolimus, Treatment of ornithine transcarbamylase deficiency): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 10 Jun 2022; EMEA-001416-PIP01-12-M03 (sirolimus, Treatment of chronic non-infectious uveitis): PM: decision on the application for modification of an agreed PIP, 11 Aug 2021; +1 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/3/25/3189 positive 9 Jan 2026: Treatment of osteosarcoma; EU/3/25/3051 positive 16 Apr 2025: Treatment of familial adenomatous polyposis (FAP); EU/3/13/1204 positive 13 Nov 2013: Prevention of arteriovenous access dysfunction in haemodialysis patients; EU/3/17/1910 positive 23 Aug 2017: Treatment of tuberous sclerosis; +10 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":"Hyftor: authorised since 15 May 2023, orphan medicine; Rapamune: authorised since 13 Mar 2001; Phelinun: authorised since 16 Nov 2020; Opsiria: application withdrawn; +1 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":"no","detail":"FDA's table lists no pediatric approval of Fludarabine Phosphate, Melphalan, Palifermin, Sirolimus","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":"2026-11-11T18:13:07.816Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"1442 interventional studies of Fludarabine Phosphate, Melphalan, Palifermin, Sirolimus include patients under 18; 367 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=%22Fludarabine+Phosphate%22+OR+%22Melphalan%22+OR+%22Palifermin%22+OR+%22Sirolimus%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T18:13:07.831Z"},"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":"City of Hope Medical Center (academic or other)","source":{"label":"ClinicalTrials.gov NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172","date":"2026-11-11T18:13:07.736Z"}},{"label":"principal investigator","text":"Monzr M Al Malki, City of Hope Medical Center","source":{"label":"Person page","url":"/person/Monzr%20M%20Al%20Malki?ind=aml","date":"2026-11-11T18:13:07.736Z"}}],"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 NCT07582172","url":"https://clinicaltrials.gov/study/NCT07582172","date":"2026-11-11T18:13:07.736Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T18:13:07.736Z"},{"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":"2026-11-11T18:13:07.731Z"}