[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657914":3},{"organization":4,"outcomesModule":7,"designInfo":37,"detailedDescription":43,"studyPopulation":36,"armGroups":44,"interventions":55,"overallOfficials":98,"centralContacts":102,"locations":108,"responsibleParty":126,"collaborators":129,"id":137,"slug":138,"hasResults":139,"nctId":140,"briefTitle":141,"officialTitle":142,"acronym":36,"eligibilityCriteria":143,"healthyVolunteers":139,"sex":144,"minAge":145,"maxAge":36,"enrollmentInfo":146,"targetDuration":36,"studyType":149,"phases":150,"briefSummary":152,"conditions":153,"keywords":36,"overallStatus":110,"whyStopped":36,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":156,"startDateStruct":159,"completionDateStruct":161,"leadSponsor":163,"locationsCount":164},{"fullName":5,"class":6},"OHSU Knight Cancer Institute","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":36},[9],{"measure":10,"description":11,"timeFrame":12},"Incidence of grade 3+ treatment-related adverse events (TRAEs)","The incidence of grade 3+ TRAEs and the total proportion of participants who experienced grade 3+ TRAEs will be estimated and presented with the corresponding 95% exact Clopper Pearson confidence intervals.","From study day 1 (week 1) to 30 days after the last dose of sirolimus",[14,18,21,24,27,29,32],{"measure":15,"description":16,"timeFrame":17},"Change in platelet count","Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.","From screening, pre dose on study day 1 (week 1) to end of treatment (EOT) (week 24, day 168)",{"measure":19,"description":16,"timeFrame":20},"Change in variant allele frequency for existing clones","From screening to end of study (EOS) (week 52, day 365)",{"measure":22,"description":16,"timeFrame":23},"Change in number of clonal hematopoiesis of indeterminate potential mutations","From screening to EOS (week 52, day 365)",{"measure":25,"description":16,"timeFrame":26},"Change in percent positivity based on activated GPIIb IIIa and surface P selectin and CD42b","From screening, pre dose on study day 1 (week 1) to EOT (week 24, day 168)",{"measure":28,"description":16,"timeFrame":26},"Change in aggregation from baseline based on thromboelastography (TEG)",{"measure":30,"description":16,"timeFrame":31},"Change in the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool score","From study day 1 (week 1) to EOS (week 52, day 365)",{"measure":33,"description":34,"timeFrame":35},"Change in the relative amount of the protein 4eBP1","Will be based on flow cytometry and immunohistochemistry assays. Descriptive statistics on continuous data will include means, medians, standard deviations and ranges, while categorical data will be summarized using frequency counts and percentages. Confidence intervals may be included, as appropriate. Graphical summaries of the data may also be presented.","From screening, pre dose on study day 1 (week 1) to EOS (week 52, day 365)",null,{"allocation":38,"interventionModel":39,"interventionModelDescription":36,"primaryPurpose":40,"observationalModel":36,"timePerspective":36,"maskingInfo":41},"NA","SINGLE_GROUP","TREATMENT",{"masking":42,"maskingDescription":36,"whoMasked":36},"NONE","PRIMARY OBJECTIVE:\n\nI. Evaluate the safety and tolerability of low-dose sirolimus in patients with RUNX1 familial platelet disorder (RUNX1-FPD).\n\nSECONDARY OBJECTIVES:\n\nI. Evaluate platelet counts. II. Evaluate changes in somatic mutation variant allele frequency (VAF). III. Evaluate somatic mutation acquisition (i.e., mutation burden). IV. Evaluate the change in platelet function. V. Evaluate the change from baseline in bleeding score (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool \\[ISTH-BAT\\]).\n\nVI. Evaluate the change in mTORC1 downstream signaling.\n\nEXPLORATORY OBJECTIVES:\n\nI. Evaluate the rescue of elevated cytokine profiles. II. Evaluate the reversal of myeloid skewing using colony formation assay. III. Evaluate monocytes using clinical flow cytometry. IV. Evaluate changes in patient-reported quality of life (QoL) outcomes measures (e.g., Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events \\[PRO-CTCAE\\]).\n\nV. Determine the pharmacokinetics of sirolimus in participants with RUNX1-FPD. VI. Evaluate the correlation between sirolimus trough levels and each endpoint. VII. Make bone marrow smears and bone marrow biopsy slides. VIII. Evaluate the cellularity of bone marrow after study treatment.\n\nOUTLINE:\n\nPatients receive sirolimus orally (PO) once daily (QD) on days 1-168 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and bone marrow biopsy and\u002For aspiration throughout the study.\n\nAfter completion of study treatment, patients are followed for 6 months.",[45],{"label":46,"type":47,"description":48,"interventionNames":49},"Treatment (sirolimus)","EXPERIMENTAL","Patients receive sirolimus PO QD on days 1-168 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and bone marrow biopsy and\u002For aspiration throughout the study.",[50,51,52,53,54],"Procedure: Biospecimen Collection","Procedure: Bone Marrow Aspiration","Procedure: Bone Marrow Biopsy","Other: Questionnaire Administration","Drug: Sirolimus",[56,66,70,76,80],{"type":57,"name":58,"description":59,"armGroupLabels":60,"otherNames":61},"PROCEDURE","Biospecimen Collection","Undergo collection of blood",[46],[62,63,64,65],"Biological Sample Collection","Biospecimen Collected","Sample Collection","Specimen Collection",{"type":57,"name":67,"description":68,"armGroupLabels":69,"otherNames":36},"Bone Marrow Aspiration","Undergo bone marrow biopsy\u002Faspiration",[46],{"type":57,"name":71,"description":68,"armGroupLabels":72,"otherNames":73},"Bone Marrow Biopsy",[46],[74,75],"Biopsy of Bone Marrow","Biopsy, Bone Marrow",{"type":6,"name":77,"description":78,"armGroupLabels":79,"otherNames":36},"Questionnaire Administration","Ancillary studies",[46],{"type":81,"name":82,"description":83,"armGroupLabels":84,"otherNames":85},"DRUG","Sirolimus","Given PO",[46],[86,87,88,89,90,91,92,93,94,95,96,97],"AY 22989","AY-22989","AY22989","RAPA","Rapamune","Rapamycin","SILA 9268A","SILA-9268A","SILA9268A","WY 090217","WY-090217","WY090217",[99],{"name":100,"affiliation":5,"role":101},"Curtis A Lachowiez","PRINCIPAL_INVESTIGATOR",[103],{"name":104,"role":105,"phone":106,"phoneExt":36,"email":107},"Knight Cancer Institute Clinical Trials Information","CONTACT","503-494-1080","trials@ohsu.edu",[109],{"facility":5,"status":110,"city":111,"state":112,"zip":113,"country":114,"countryCode":115,"cosmosGeoPoint":116,"geoPoint":121,"contacts":122},"RECRUITING","Portland","Oregon","97239","United States","US",{"type":117,"coordinates":118},"Point",[119,120],-122.67621,45.52345,{"lat":120,"lon":119},[123,124],{"name":104,"role":105,"phone":106,"phoneExt":36,"email":107},{"name":125,"role":101,"phone":36,"phoneExt":36,"email":36},"Curtis A. Lachowiez",{"type":101,"investigatorFullName":127,"investigatorTitle":128,"investigatorAffiliation":5,"oldNameTitle":36,"oldOrganization":36},"Curtis Lachowiez","Principal Investigator",[130,133,135],{"name":131,"class":132},"National Cancer Institute (NCI)","NIH",{"name":134,"class":6},"Oregon Health and Science University",{"name":136,"class":6},"M.D. Anderson Cancer Center","100657914","early-phase-1-low-dose-sirolimus-for-the-treatment-of-runx1-familial-platelet-disorder-100657914",false,"NCT07844694","Low-Dose Sirolimus for the Treatment of RUNX1 Familial Platelet Disorder","Low-Dose Sirolimus to Increase Hematopoietic Function in Patients With RUNX1 Familial Platelet Disorder - Part II","Inclusion Criteria:\n\n* Patient has provided signed, informed consent before initiation of any study specific procedures\n* Aged ≥ 18 years at the time of signing the informed consent\n* Confirmed pathogenic\u002Flikely pathogenic (P\u002FLP) germline RUNX1 variant per ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) RUNX1-specific variant curation rules\n* Patient must be willing to provide a bone marrow sample at time of screening and at the end of treatment with sirolimus\n* Platelet count of ≥ 50,000\u002FµL\n* Creatinine clearance (CrCl) of ≥ 60 mL\u002Fmin; estimated using the Cockcroft Gault formula or measured by 24 hour urine collection. Exceptions will be allowed, at the discretion of the investigator, for cases of a concomitant medication that alters renal function\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C 3 × upper limit of normal (ULN)\n* Total bilirubin \\\u003C 1.5 × ULN\n* Left ventricular ejection fraction (EF) \\> 50% or at the discretion of the investigator\n\nExclusion Criteria:\n\n* Known allergy to sirolimus\n* History of major bleeding events that are clinically relevant in the judgement of the investigator or non-major bleeding events that cannot be controlled using SOC practices\n* Any known history of lymphoma, myelodysplastic syndrome (MDS), or other hematologic malignancy using International Working Group criteria\n* Prior treatment with sirolimus or a rapalog, mTOR inhibitor, or B-cell-depleting therapy within 28 days before study day 1\n* Treatment with strong inhibitors of cytochrome P450 3A4 (CYP3A4; e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, and clarithromycin), strong inducers of CYP3A4 (e.g., rifampin and rifabutin), other drugs that could increase sirolimus blood concentrations (e.g., bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, letermovir, protease inhibitors \\[e.g., ritonavir, indinavir, boceprevir, and telaprevir\\], metoclopramide, nicardipine, troleandomycin, and verapamil), other drugs that could decrease sirolimus blood concentrations (e.g., carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort \\[Hypericum perforatum\\]), or drugs with blood concentrations that could increase (e.g., verapamil) within 7 days before study day 1, or at the discretion of the investigator\n* Use of cannabidiols that increase blood levels of sirolimus, within 7 days before study day 1 or at the discretion of the investigator\n* Myocardial infarction within 6 months before study day 1, congestive heart failure (New York Heart Association \\> class II)\n* Total cholesterol \\> 300 mg\u002FdL or triglyceride \\> 400 mg\u002FdL\n* Arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months before study day 1\n* Infection requiring intravenous anti-infective treatment within 1 week of study day 1\n* Live vaccines (e.g., measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin \\[BCG\\], yellow fever, varicella, and TY21a typhoid) within 28 days before study day 1\n* Known diagnosis of tuberculosis is exclusionary to provide protection against reactivation of infections by the immunosuppressive activity of the study drug sirolimus\n\n  * The enrollment of a patient with a history of infection with hepatitis B virus (HBV) but with undetectable HBV deoxyribonucleic acid (DNA) by standard institutional testing can be considered after consultation with the investigator\n  * Patients with history of chronic hepatitis C virus (HCV) must have documentation of completed curative standard of care (SOC) antiviral therapy\n  * Patients with history of HIV infection must be well-managed with SOC antiretroviral therapy (highly active antiretroviral therapy \\[HAART\\])\n  * Patients with history of Epstein-Barr may be considered after consultation with the treating physician\n* Participants who are pregnant may become pregnant, or who are breastfeeding\n\n  * Because adequate and well-controlled studies of the impact of sirolimus on fetuses currently do not exist, study approved contraception must be used from start of study therapy to 12 weeks after the last dose of sirolimus\n  * Adequate and well-controlled studies of infants fed breastmilk from patients undergoing sirolimus therapy do not exist and breastfeeding during study treatment is prohibited","ALL","18 Years",{"count":147,"type":148},6,"ESTIMATED","INTERVENTIONAL",[151],"PHASE1","This phase I trial studies the safety and side effects of low-dose sirolimus in treating patients with RUNX1 familial platelet disorder (FPD). RUNX1-FPD is a rare inherited disorder with symptoms such as mild to moderately low platelet count, abnormal platelet function, and an increased risk of developing cancers like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is caused by changes (variants) in the RUNX1 gene that is passed down (inherited) from an affected parent. Sirolimus is typically given to help prevent organ rejection in patients receiving kidney transplants. However, sirolimus may also be able to prevent RUNX1-FPD from progressing to cancers like MDS and AML by targeting another protein called mTORC1. Sirolimus may be a safe treatment for patients with RUNX1-FPD.",[154],"Familial Platelet Disorder With Associated Myeloid Malignancy","2026-10-07",{"date":157,"type":158},"2026-10-13","ACTUAL",{"date":160,"type":158},"2026-10-05",{"date":162,"type":148},"2030-12-31",{"name":5,"class":6},1]