[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT05308264":3,"trial-entities:NCT05308264":217,"trial-summary:NCT05308264":222},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":31,"interventions":34,"primary_outcomes":43,"secondary_outcomes":48,"sex":57,"minimum_age":58,"maximum_age":59,"healthy_volunteers":15,"eligibility_criteria":60,"std_ages":89,"locations":92,"central_contacts":208,"overall_officials":214,"references":215,"see_also_links":216},"NCT05308264","C-906289-002","Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)","An Open-label, Phase 1b Study of R289, an IRAK1\u002F4 Inhibitor, in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS) Who Are Relapsed\u002FRefractory\u002FResistant to Prior Therapies","RECRUITING","2026-12","2025-10","2026-08-10","2022-09-12","Rigel Pharmaceuticals","INDUSTRY",false,"Phase 1b Study of R289 in Patients with Lower-risk Myelodysplastic Syndromes (LR MDS)","An open-label, Phase 1b study of R289, an IRAK 1\u002F4 Inhibitor, to determine tolerability and preliminary efficacy in patients with LR MDS who are relapsed\u002Frefractory\u002Fresistant, intolerant, or have inadequate response to prior therapies such as erythropoietin (EPO), luspatercept, or hypomethylating agents (HMAs) for MDS.",[19],"Low Risk Myelodysplastic Syndromes",[21,22,23,24,25],"MDS","LR MDS","Myelodysplastic Syndromes","Hematology Oncology","Hem\u002F Onc","INTERVENTIONAL","TREATMENT",[29,30],"PHASE1","PHASE2",{"count":32,"type":33},86,"ESTIMATED",[35],{"type":36,"name":37,"description":38,"armGroupLabels":39,"otherNames":41},"DRUG","R906289 Monosodium (R289 Na)","Drug: R906289 Monosodium (R289 Na) R906289 Monosodium (250mg PO qd, 250mg PO bid, 500 mg PO qd, 500 mg PO bid, 750 mg PO qd, split dose - 500 mg PO AM\u002F250 mg PO PM)",[40],"Experimental",[42],"R906289 Monosodium",[44],{"measure":45,"description":46,"timeFrame":47},"Safety and Tolerability","* Incidence of adverse events (AEs)\n* Incidence of discontinuation or interruptions of R289 due to AEs\n* Incidence of dose limiting toxicities (DLTs)","2 Year",[49,53],{"measure":50,"description":51,"timeFrame":52},"Outcome Measure: Preliminary Efficacy","Measure Description Primary Efficacy:\n\nProportion of patients achieving red blood cell transfusions independence by ≥ 8 weeks, ≥ 16 weeks, and ≥ 24 weeks Proportion of patients with overall response per IWG 2006 Proportion of patients with hematologic improvement per IWG 2018 Time Frame: 24 Weeks Measure Description Characterized PK Maximum plasma concentration (Cmax) Time Frame: 8 Weeks","24 Weeks for Primary Efficacy; 8 Weeks for Characterized PK",{"measure":54,"description":55,"timeFrame":56},"Characterize pharmacokinetics (PK)","Maximum plasma concentration (Cmax)","8 Weeks","ALL","18 Years",null,{"inclusion":61,"exclusion":73,"raw_text":88},[62,63,64,65,66,67,68,69,70,71,72],"Patient must be ≥ 18 years of age at the time of signing the informed consent.","Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.","Must be relapsed, refractory\u002Fresistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.","DOSE ESCALATION PHASE:","DOSE EXPANSION PHASE:","EXPLORATORY PHASE 1b COHORT:","All patients must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be \\>20% or a serum ferritin \\> 100ng\u002F100mL","Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.","Must have adequate organ function, defined as:","aspartate amino transferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)","total bilirubin ≤ 1.5 × ULN 2. Renal function defined as creatinine clearance \\> 60 mL\u002Fmin (using Cockcroft-Gault), or blood creatine \\\u003C 1.5 mg\u002FdL",[74,75,76,77,78,79,80,81,82,83,84,85,86,87],"Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded \\\u003C 4 weeks prior to study treatment","Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.","MDS secondary to treatment with radiotherapy, chemotherapy, and\u002For immunotherapy for malignant or autoimmune diseases.","Diagnosis of chronic myelomonocytic leukemia.","History of uncontrolled seizures.","Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).","History of other malignancy that could affect compliance or interpretation of results. Patients with an malignancy other than leukemia appropriately treated with curative intent and the malignancy has been in remission without treatment for ≥ 2 years prior to study entry are eligible as are:","History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion (or following review by the Sponsor), could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.","Prior history of autologous or allogeneic stem cell transplantation","Marked baseline prolongation of QT\u002FQTc interval (e.g., repeated demonstration of a QTc interval \\> 480 milliseconds \\[msec\\]) (Common Terminology Criteria for Adverse Events \\[CTCAE\\] Grade 1) using Fridericia's QT correction formula.","History of additional risk factors for TdP (e.g., symptomatic heart failure with left ventricular ejection fraction \\[LVEF\\] \\\u003C40%, hypokalemia, family history of Long QT Syndrome).","Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet. For any long-acting systemic agent such as a monoclonal antibody, study treatment should not begin within two half-lives of the agent.","Use of concomitant medications that prolong the QT\u002FQTc interval during study treatment","Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment","Inclusion Criteria:\n\n* Patient must be ≥ 18 years of age at the time of signing the informed consent.\n* Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.\n* Must be relapsed, refractory\u002Fresistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.\n* DOSE ESCALATION PHASE:\n\n  a. Must meet at least one of the following criteria prior to initial administration of study treatment: 1) Symptomatic anemia with hemoglobin \\\u003C 9.0 g\u002FdL and no RBC transfusion within 16 of registration or 2) RBC transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin \\\u003C9.0 g\u002FdL.\n* DOSE EXPANSION PHASE:\n\n  1. Relapsed, refractory to or ineligible for ESAs and has previously received one or more approved therapies for LR-MDS\n  2. Must be RBC transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin \\\u003C9.0 g\u002FdL.\n* EXPLORATORY PHASE 1b COHORT:\n\n  1. Transfusion-dependent LR-MDS who are refractory or intolerant to, or are ineligible for ESAs.\n  2. No prior therapy with any approved or investigational therapies for MDS\n  3. No del 5q cytogenetic abnormality\n  4. RBC transfusion dependent defined as receiving ≥ 2 units of PRBCs within 8 weeks in the preceding 16 weeks for a hemoglobin \\\u003C9.0 g\u002FdL\n* All patients must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be \\>20% or a serum ferritin \\> 100ng\u002F100mL\n* Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.\n* Must have adequate organ function, defined as:\n\n  1. Hepatic function:\n\n     * aspartate amino transferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)\n     * total bilirubin ≤ 1.5 × ULN\n  2. Renal function defined as creatinine clearance \\> 60 mL\u002Fmin (using Cockcroft-Gault), or blood creatine \\\u003C 1.5 mg\u002FdL\n\nExclusion Criteria:\n\n* Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded \\\u003C 4 weeks prior to study treatment\n* Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.\n* MDS secondary to treatment with radiotherapy, chemotherapy, and\u002For immunotherapy for malignant or autoimmune diseases.\n* Diagnosis of chronic myelomonocytic leukemia.\n* History of uncontrolled seizures.\n* Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).\n* History of other malignancy that could affect compliance or interpretation of results. Patients with an malignancy other than leukemia appropriately treated with curative intent and the malignancy has been in remission without treatment for ≥ 2 years prior to study entry are eligible as are:\n\n  1. Adequately treated in situ carcinoma of the cervix uteri\n  2. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or\n  3. Low grade, early-stage prostate cancer (Gleason score 6 or below, stage 1 or 2) with no requirement for therapy at any time prior to the study, or previously resected.\n* History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion (or following review by the Sponsor), could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.\n* Prior history of autologous or allogeneic stem cell transplantation\n* Marked baseline prolongation of QT\u002FQTc interval (e.g., repeated demonstration of a QTc interval \\> 480 milliseconds \\[msec\\]) (Common Terminology Criteria for Adverse Events \\[CTCAE\\] Grade 1) using Fridericia's QT correction formula.\n* History of additional risk factors for TdP (e.g., symptomatic heart failure with left ventricular ejection fraction \\[LVEF\\] \\\u003C40%, hypokalemia, family history of Long QT Syndrome).\n* Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet. For any long-acting systemic agent such as a monoclonal antibody, study treatment should not begin within two half-lives of the agent.\n* Use of concomitant medications that prolong the QT\u002FQTc interval during study treatment\n* Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment",[90,91],"ADULT","OLDER_ADULT",[93,102,109,116,124,132,140,148,155,162,170,178,185,193,200],{"facility":94,"status":8,"city":95,"state":96,"zip":97,"country":98,"geoPoint":99},"University of California, Los Angeles","Los Angeles","California","90095","United States",{"lat":100,"lon":101},34.05223,-118.24368,{"facility":103,"status":8,"city":104,"state":96,"zip":105,"country":98,"geoPoint":106},"University of California, Irvine","Orange","92868",{"lat":107,"lon":108},33.78779,-117.85311,{"facility":110,"status":8,"city":111,"state":96,"zip":112,"country":98,"geoPoint":113},"Stanford Cancer Institute","Palo Alto","94304",{"lat":114,"lon":115},37.44188,-122.14302,{"facility":117,"status":8,"city":118,"state":119,"zip":120,"country":98,"geoPoint":121},"University of Miami","Miami","Florida","33136",{"lat":122,"lon":123},25.77427,-80.19366,{"facility":125,"status":126,"city":127,"state":119,"zip":128,"country":98,"geoPoint":129},"Mount Sinai Medical Center","WITHDRAWN","Miami Beach","33140",{"lat":130,"lon":131},25.79065,-80.13005,{"facility":133,"status":8,"city":134,"state":135,"zip":136,"country":98,"geoPoint":137},"WashU Medicine","St Louis","Missouri","63110",{"lat":138,"lon":139},38.62727,-90.19789,{"facility":141,"status":8,"city":142,"state":143,"zip":144,"country":98,"geoPoint":145},"Oncology Clinical Research Referral Office","Hackensack","New Jersey","07601",{"lat":146,"lon":147},40.88593,-74.04347,{"facility":149,"status":126,"city":150,"state":143,"zip":151,"country":98,"geoPoint":152},"Rutgers Cancer Institute of New Jersey","New Brunswick","09083",{"lat":153,"lon":154},40.48622,-74.45182,{"facility":156,"status":8,"city":157,"state":157,"zip":158,"country":98,"geoPoint":159},"Ichan School of Medicine at Mount Sinai","New York","10029",{"lat":160,"lon":161},40.71427,-74.00597,{"facility":163,"status":8,"city":164,"state":165,"zip":166,"country":98,"geoPoint":167},"Duke Cancer Institute","Durham","North Carolina","27705",{"lat":168,"lon":169},35.99403,-78.89862,{"facility":171,"status":8,"city":172,"state":173,"zip":174,"country":98,"geoPoint":175},"Cleveland Clinic","Cleveland","Ohio","44195",{"lat":176,"lon":177},41.4995,-81.69541,{"facility":179,"status":8,"city":180,"state":173,"zip":181,"country":98,"geoPoint":182},"The Ohio State University Comprehensive Cancer Center","Columbus","43210",{"lat":183,"lon":184},39.96118,-82.99879,{"facility":186,"status":8,"city":187,"state":188,"zip":189,"country":98,"geoPoint":190},"University of Texas, Southwestern","Dallas","Texas","75390",{"lat":191,"lon":192},32.78306,-96.80667,{"facility":194,"status":8,"city":195,"state":188,"zip":196,"country":98,"geoPoint":197},"MD Anderson Cancer Center","Houston","77030",{"lat":198,"lon":199},29.76328,-95.36327,{"facility":201,"status":8,"city":202,"state":203,"zip":204,"country":98,"geoPoint":205},"Intermountain Healthcare","Salt Lake City","Utah","84009",{"lat":206,"lon":207},40.76078,-111.89105,[209],{"name":210,"role":211,"phone":212,"email":213},"Strait Hicklin","CONTACT","(650) 624-1100","shicklin@rigel.com",[],[],[],{"nct_id":4,"conditions":218,"biomarkers":220},[219],"Myelodysplastic Syndrome",[221],"marrow iron",{"nct_id":4,"found":223,"summary":224,"prompt_version":59},true,{"design":225,"status":226,"heading":227,"summary":228,"follow_up":229,"word_count":230,"commitments":231,"compensation":232,"drugs_mentioned":233},"This is an open-label, Phase 1b study, meaning both you and the study team will know which treatment you are receiving. It plans to enroll 86 participants.","completed","Study of R289 for Lower-risk Myelodysplastic Syndromes","This study is testing a drug called R289 Monosodium (R289 Na) for people with lower-risk Myelodysplastic Syndromes (MDS). MDS is a group of conditions where your bone marrow doesn't make enough healthy blood cells. This study is for adults aged 18 or older who have lower-risk MDS and whose previous treatments, like erythropoietin (EPO), luspatercept, or hypomethylating agents (HMAs), haven't worked well or they couldn't tolerate them. The main goal is to see how safe R289 Monosodium is and if people can tolerate it over two years. The study also aims to see if the drug shows early signs of helping patients.","The safety and tolerability of the drug will be measured for up to two years.",102,"Not specified in the trial record.","Not stated in the trial record.",[]]