[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100515033":3},{"organization":4,"armGroups":7,"interventions":19,"overallOfficials":34,"centralContacts":38,"locations":44,"responsibleParty":75,"collaborators":77,"id":83,"slug":84,"hasResults":85,"nctId":86,"briefTitle":87,"officialTitle":88,"acronym":42,"eligibilityCriteria":89,"healthyVolunteers":90,"sex":91,"minAge":92,"maxAge":42,"enrollmentInfo":93,"targetDuration":42,"studyType":96,"phases":97,"briefSummary":99,"conditions":100,"keywords":42,"overallStatus":46,"whyStopped":42,"lastUpdateSubmitDate":104,"lastUpdatePostDateStruct":105,"startDateStruct":108,"completionDateStruct":110,"leadSponsor":112,"locationsCount":113},{"fullName":5,"class":6},"Montefiore Medical Center","OTHER",[8,14],{"label":9,"type":10,"description":11,"interventionNames":12},"Danvatirsen Monotherapy","EXPERIMENTAL","Patients will be enrolled in cohorts of 3 for the Danvatirsen dose escalation substudy. Based on the DLT of the first cohort of participants, subsequent cohorts will either be administered doses at the next higher dose level, de-escalated to the next lower dose level, or remain the same. Dose escalation discontinuations and MTD will be determined as described in the 'Detailed Study Description.' The total duration of 1 cycle is approximately 4 weeks (28 days). Proposed dose levels and treatment schedule are as follows:\n\nDose Level 1 (DL1): Danvatirsen Day 1 - Day 28 (1mg\u002Fkg loading dose on Cycle 1\u002FDay 1 (C1D1), Cycle 1\u002FDay 3 (C1D3); and Cycle 1\u002FDay 5 (C1D5) followed by weekly 1mg\u002Fkg infusion for 3 weeks) Dose Level 2 (DL2): Danvatirsen Day 1 - Day 28 (2mg\u002Fkg loading dose on C1D1, C1D3, and C1D5 followed by weekly 2mg\u002Fkg infusion for 3 weeks) Dose Level 3 (DL3): Danvatirsen Day 1 - Day 28 (3mg\u002Fkg loading dose on C1D1, C1D3, and C1D5 followed by weekly 3mg\u002Fkg infusion for 3 weeks)",[13],"Drug: Danvatirsen",{"label":15,"type":10,"description":16,"interventionNames":17},"Danvatirsen + Venetoclax Combination Therapy","Patients will be enrolled in cohorts of 3 for the Danvatirsen + Venetoclax dose escalation substudy. Dose escalation administration will be as described in the Danvatirsen monotherapy substudy arm and dose escalation discontinuations and MTD will be determined as described in the 'Detailed Study Description.'\n\nUp to 2 dose levels of Danvatirsen will be evaluated based on data from the Danvatirsen monotherapy arm. Dose 1 will be one level lower than the dose with expected target activity.\n\nVenetoclax: 400 mg (or equivalent) administered as fixed dose daily (except for specific dose modifications described in the protocol) orally for 28 days per cycle. To mitigate risk of tumor lysis syndrome, during Cycle 1 Venetoclax will be dose escalated daily to the goal dose of 400mg daily (100mg on Day 1, 200mg on Day 2 and 400mg on Day 3, and onwards, or adjusted dose ramp-up per Venetoclax label if on concomitant azoles).\n\nThe three cycles are approximately 28 days each in duration.",[18],"Combination Product: Danvatirsen + Venetoclax",[20,27],{"type":21,"name":22,"description":23,"armGroupLabels":24,"otherNames":25},"DRUG","Danvatirsen","Danvatirsen (AZD9150) is a selective, high-affinity, antisense oligonucleotide inhibitor of signal transducer and activator of transcription 3 (or STAT3).",[9],[26],"AZD9150",{"type":28,"name":29,"description":30,"armGroupLabels":31,"otherNames":32},"COMBINATION_PRODUCT","Danvatirsen + Venetoclax","Danvatirsen (AZD9150) is a selective, high-affinity, antisense oligonucleotide inhibitor of signal transducer and activator of transcription 3 (or STAT3).\n\nVenetoclax: Commercially available. Venetoclax is a potent, selective small molecule inhibitor of BCL-2, an anti-apoptotic protein found on some types of cancer cells.",[15],[33],"Venclexta",[35],{"name":36,"affiliation":5,"role":37},"Aditi Shastri, MBBS","PRINCIPAL_INVESTIGATOR",[39],{"name":36,"role":40,"phone":41,"phoneExt":42,"email":43},"CONTACT","718-920-4826",null,"ashastri@montefiore.org",[45,60],{"facility":5,"status":46,"city":47,"state":48,"zip":49,"country":50,"countryCode":51,"cosmosGeoPoint":52,"geoPoint":57,"contacts":58},"RECRUITING","The Bronx","New York","10467","United States","US",{"type":53,"coordinates":54},"Point",[55,56],-73.86641,40.84985,{"lat":56,"lon":55},[59],{"name":36,"role":40,"phone":41,"phoneExt":42,"email":43},{"facility":61,"status":46,"city":62,"state":63,"zip":64,"country":50,"countryCode":51,"cosmosGeoPoint":65,"geoPoint":69,"contacts":70},"M.D. Anderson Cancer Center, Department of Leukemia","Houston","Texas","77030",{"type":53,"coordinates":66},[67,68],-95.36327,29.76328,{"lat":68,"lon":67},[71],{"name":72,"role":40,"phone":73,"phoneExt":42,"email":74},"Naval Daver, MD","713-794-4392","ndaver@mdanderson.org",{"type":76,"investigatorFullName":42,"investigatorTitle":42,"investigatorAffiliation":42,"oldNameTitle":42,"oldOrganization":42},"SPONSOR",[78,80],{"name":79,"class":6},"M.D. Anderson Cancer Center",{"name":81,"class":82},"Flamingo Therapeutics NV","INDUSTRY","100515033","phase-1-danvatirsen-monotherapy-followed-by-combination-with-venetoclax-in-relapsedrefractory-mds--aml-100515033",false,"NCT05986240","Danvatirsen Monotherapy Followed by Combination With Venetoclax in Relapsed\u002FRefractory MDS & AML","A Phase I Study Investigating the Safety & Efficacy of Danvatirsen as Monotherapy Followed by Combination With Venetoclax in Patients With Relapsed\u002FRefractory MDS & AML","Inclusion Criteria:\n\n* Subjects must be at least 18 years of age at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and be able to meet all study requirements\n* Morphologically confirmed diagnosis of AML or MDS in accordance with World Health Organization (WHO) diagnostic criteria\n* Subjects with relapsed\u002Frefractory AML who are refractory or relapsed to all conventional therapy and do not have any FDA approved or standard therapeutic options \\& subjects with intermediated\u002Fhigh\u002Fvery high IPSS-R MDS who are refractory or relapsed to at least 2 cycles of hypomethylating agent based therapy (azacitidine \u002F decitabine based) OR patients with rapid progression of disease regardless of number of cycles of therapy\n* At least 3 months from Allogenic stem cell transplantation and no clinical sign of active graft vs host disease (GVHD)\n* WBC must be \\\u003C25,000 cells\u002FuL and may be reduced with hydroxyurea to reach this goal prior to study start. Hydroxyurea can be administered on trial with an increase in WBC counts at the discretion of the PI\n* A bone marrow biopsy must be performed within the screening window (day-28-day-1) and tissue collected for correlative analysis for entrance to this trial. Correlative sample collection is essential on this study\n* Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2\n* Recovery to ≤ Grade 1 or baseline for any toxicities considered to be due to prior systemic treatments, excluding alopecia\n* Must have adequate hepatic and renal function as follows:\n\nALT (SGPT) and\u002For AST (SGOT) ≤ 3x upper limit of normal (ULN) or ≤ 5x ULN if considered to be leukemia related; Direct bilirubin ≤ 1.5 x ULN or ≤ 3x ULN (in patients with known Gilberts syndrome or if considered to be leukemia related)\n\n* Serum creatinine clearance ≥ 45 mL\u002Fmin\u002F1.73 m2 either measured or calculated using standard Cockroft-Gault formula\n* Subjects enrolled within childbearing ages of 18-50 years should use 2 forms of contraception while on study\n\nExclusion Criteria:\n\n* Acute Promyelocytic Leukemia\n* Low or very low risk MDS by IPSS-R after failure\u002Fprogression of first line therapy with hypomethylating agents\n* Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Use of prophylactic anti-microbials per institutional standards is allowed\n* Active documented central nervous system (CNS) leukemia. Patients with a known history of CNS leukemia will be eligible if they have at least two most recent consecutive LPs showing clearance of CNS disease and no active\u002Fprogressive symptoms thought to be related to the CNS disease\n* Concurrent treatment with a non-permitted concomitant medication (as noted in protocol appendix)\n* Concurrent anticancer treatment, major surgery, or the use of any investigational drug within 14 days before the start of trial treatment\n* Other malignancy currently being treated or likely to need treatment in next 6 months with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ, surgically removed malignancies or malignancies definitively treated with chemotherapy, XRT and\u002For surgery with no evidence of active malignancy or not anticipated to need treatment in next 6 months or malignancies on maintenance therapy (e.g. tamoxifen for breast cancer) will be allowed after discussion and approval by both MPIs\n* Pregnant or breastfeeding females\n* Known current alcohol or drug abuse\n* Clinically significant cardiovascular disease within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented NYHA class III\u002FIV cardiac heart failure, unstable angina or MI, poorly controlled atrial or ventricular arrhythmia) as determined by the investigator\n* Any psychiatric condition that would prohibit the understanding or rendering of informed consent\n* Legal incapacity or limited legal capacity to sign consent and\u002For participate in the trial\n* Any condition deemed by the investigator to make the patient a poor candidate for clinical trial and\u002For treatment with investigational agents\n* Previous exposure to the investigational agent (danvatirsen)",true,"ALL","18 Years",{"count":94,"type":95},38,"ESTIMATED","INTERVENTIONAL",[98],"PHASE1","This is a Phase 1 study investigating the safety and efficacy of Danvatirsen as a monotherapy followed by combination with Venetoclax in patients with relapsed\u002Frefractory myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).\n\nFunding Source: FDA OOPD",[101,102,103],"AML\u002FMDS","Acute Myeloid Leukemia","Myelodysplastic Syndromes","2025-11-06",{"date":106,"type":107},"2025-11-10","ACTUAL",{"date":109,"type":107},"2024-05-08",{"date":111,"type":95},"2030-03",{"name":5,"class":6},2]