[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07008638":3,"trial-entities:NCT07008638":128,"trial-summary:NCT07008638":132},{"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":21,"study_type":22,"primary_purpose":23,"phases":24,"enrollment_info":27,"interventions":30,"primary_outcomes":48,"secondary_outcomes":56,"sex":71,"minimum_age":72,"maximum_age":17,"healthy_volunteers":73,"eligibility_criteria":74,"std_ages":100,"locations":103,"central_contacts":119,"overall_officials":125,"references":126,"see_also_links":127},"NCT07008638","2024LS157","Phase I\u002FII Clinical Trial of Proteasome Inhibitor in Combination With CPX-351 for the Treatment of Newly-Diagnosed TP53-mutated Acute Myeloid Leukemia (AML)","HM2024-29: Phase I\u002FII Clinical Trial of Proteasome Inhibitor in Combination With CPX-351 for the Treatment of Newly-Diagnosed TP53-mutated Acute Myeloid Leukemia (AML)","RECRUITING","2028-01-27","2026-07","2026-07-22","2025-07-07","Masonic Cancer Center, University of Minnesota","OTHER",true,"This is a Phase I\u002FII study evaluating safety and efficacy of proteasome inhibitor (bortezomib) in combination with CPX-351 (liposomal daunorubicin and cytarabine) for the treatment of newly-diagnosed TP53-mutated acute myeloid leukemia (TP53m AML).\n\nThe primary endpoint of the study is to define safety\u002Ftolerability (phase I) and preliminary efficacy profile (phase II) of the treatment. The secondary endpoints of interest are complete remission (CR) rate, detectable minimal residual disease (MRD) status, overall response rate (ORR), rate of allogeneic hematopoietic cell transplantation (allo-HCT), treatment-related mortality (TRM), overall survival (OS), achievement of complete remission anytime in 1 year, and disease-free survival (DFS) at 1 year and 2 years. All the patient outcomes assessments will be performed as part of standard-of-care AML management.\n\nThe hypothesis is the combination of bortezomib and CPX-351 will have an acceptable safety profile in this patient population based on the data from previous studies. The treatment will attenuate Nuclear Factor kB pathway activation in these cells and eradicate TP53m leukemia stem cells (LSC) leading to increased response rate and survival in these patients.",null,[19,20],"Acute Myeloid Leukemia","TP53",[],"INTERVENTIONAL","TREATMENT",[25,26],"PHASE1","PHASE2",{"count":28,"type":29},32,"ESTIMATED",[31,41],{"type":32,"name":33,"description":34,"armGroupLabels":35},"DRUG","Bortezomib","Bortezomib at assigned study dose in mg\u002Fm2 will be given subcutaneously on days 1, 4, 8, and 11",[36,37,38,39,40],"Phase 1: Dose Level -1","Phase 1: Dose Level 2","Phase 1: Dose Level 3","Phase 1: Dose Level 4","Phase 2",{"type":32,"name":42,"description":43,"armGroupLabels":44,"otherNames":45},"CPX-351","CPX-351 given intravenously on day 1, 3, and 5",[36,37,38,39,40],[46,47],"Liposomal daunorubicin","Cytarabine",[49,53],{"measure":50,"description":51,"timeFrame":52},"Percentage of Participants with Complete Response","To evaluate the CR rate of bortezomib + CPX-351 for the treatment of TP53m AML.","2 years",{"measure":54,"timeFrame":55},"Determine Maximum Tolerated Dose","1 year",[57,60,63,66,68],{"measure":58,"description":59,"timeFrame":52},"Determine Overall Response Rate","Evaluate ORR (CR+CRi) after treatment",{"measure":61,"description":62,"timeFrame":52},"Average rate of allo-HCT among participants","Evaluate the rate of allo-HCT within 2 years among patients who received treatment",{"measure":64,"description":65,"timeFrame":55},"Overall Survival","estimate 1-year and 2-year OS, defined as the time from cohort assignment to death from any cause",{"measure":64,"description":65,"timeFrame":67},"2 year",{"measure":69,"description":70,"timeFrame":67},"Average time to relapse","• To estimate time to relapse, defined as the time from cohort assignment to disease recurrence","ALL","18 Years",false,{"inclusion":75,"exclusion":85,"raw_text":99},[76,77,78,79,80,81,82,83,84],"Adult (age ≥ 18 years at time of consent)","Have not received any systemic chemotherapy for the treatment of AML. Use of hydroxyurea and leukapheresis to control excess peripheral blasts is permissible. WBC \\\u003C 25,000 to initiate bortezomib, must reach this threshold by day 7 of CPX-351.","Karnofsky performance status (KPS) ≥ 70","Adequate renal, hepatic and cardiac function defined as","Renal: An estimated glomerular filtration rate ≥ 30 mL\u002Fmin\u002F1.73 m2","Hepatic: AST and ALT ≤3 x ULN, ALP ≤2.5 x ULN, and total bilirubin ≤1.5 x ULN. (exception for Gilbert's syndrome or leukemic infiltration of liver)","Cardiac: New York Heart Association (NYHA) Class I or II, left ventricular ejection fraction \\> 50% by echocardiogram, MUGA or cardiac MRI","Sexually active couples of childbearing potential must agree to use effective contraception or abstinence during treatment and for at least 7 months after the final dose of study drug","Provides voluntary written consent before the performance of any study related activities not part of standard of care.",[86,87,88,89,90,91,92,93,94,95,96,97,98],"Received systemic chemotherapy for the treatment of AML","Bi-phenotypic acute leukemia or mixed lineage leukemia, acute promyelocytic leukemia","Active central nervous system malignancy or symptoms of CNS involvement","Symptomatic extramedullary disease","Known history of uncontrolled HIV or active hepatitis B or active hepatitis C infection","Has any of the following cardiac abnormalities","Symptomatic congestive heart failure","Myocardial infarction less than or equal to 6 months prior to enrollment","Unstable angina pectoris","Serious uncontrolled cardiac arrhythmia","Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Potential participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis","Participants for whom administration of CPX-351 would exceed their lifetime cumulative daunorubicin exposure limit of 550 mg\u002Fm2 (or 400 mg\u002Fm2 in patients with prior chest radiation) or equivalent anthracycline dose.","Pregnant or breastfeeding, or planning pregnancy within 3 months after the treatment completion","Inclusion Criteria:\n\n* Adult (age ≥ 18 years at time of consent)\n* Have not received any systemic chemotherapy for the treatment of AML. Use of hydroxyurea and leukapheresis to control excess peripheral blasts is permissible. WBC \\\u003C 25,000 to initiate bortezomib, must reach this threshold by day 7 of CPX-351.\n* Karnofsky performance status (KPS) ≥ 70\n* Adequate renal, hepatic and cardiac function defined as\n* Renal: An estimated glomerular filtration rate ≥ 30 mL\u002Fmin\u002F1.73 m2\n* Hepatic: AST and ALT ≤3 x ULN, ALP ≤2.5 x ULN, and total bilirubin ≤1.5 x ULN. (exception for Gilbert's syndrome or leukemic infiltration of liver)\n* Cardiac: New York Heart Association (NYHA) Class I or II, left ventricular ejection fraction \\> 50% by echocardiogram, MUGA or cardiac MRI\n* Sexually active couples of childbearing potential must agree to use effective contraception or abstinence during treatment and for at least 7 months after the final dose of study drug\n* Provides voluntary written consent before the performance of any study related activities not part of standard of care.\n\nExclusion Criteria:\n\n* Received systemic chemotherapy for the treatment of AML\n* Bi-phenotypic acute leukemia or mixed lineage leukemia, acute promyelocytic leukemia\n* Active central nervous system malignancy or symptoms of CNS involvement\n* Symptomatic extramedullary disease\n* Known history of uncontrolled HIV or active hepatitis B or active hepatitis C infection\n* Has any of the following cardiac abnormalities\n* Symptomatic congestive heart failure\n* Myocardial infarction less than or equal to 6 months prior to enrollment\n* Unstable angina pectoris\n* Serious uncontrolled cardiac arrhythmia\n* Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Potential participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis\n* Participants for whom administration of CPX-351 would exceed their lifetime cumulative daunorubicin exposure limit of 550 mg\u002Fm2 (or 400 mg\u002Fm2 in patients with prior chest radiation) or equivalent anthracycline dose.\n* Pregnant or breastfeeding, or planning pregnancy within 3 months after the treatment completion",[101,102],"ADULT","OLDER_ADULT",[104],{"facility":105,"status":8,"city":106,"state":107,"zip":108,"country":109,"contacts":110,"geoPoint":116},"Masonic Cancer Center","Minneapolis","Minnesota","55455","United States",[111],{"name":112,"role":113,"phone":114,"email":115},"Joseph Norton, DO","CONTACT","(612) 626-3107","norto491@umn.edu",{"lat":117,"lon":118},44.97997,-93.26384,[120,121],{"name":112,"role":113,"phone":114,"email":115},{"name":122,"role":113,"phone":123,"email":124},"Zohar Sachs, MD, PhD","612-626-7055","sachs038@umn.edu",[],[],[],{"nct_id":4,"conditions":129,"biomarkers":130},[19],[131],"TP53 Gene",{"nct_id":4,"found":15,"summary":133,"prompt_version":143},{"design":134,"status":135,"heading":136,"summary":137,"follow_up":138,"word_count":139,"commitments":140,"compensation":141,"drugs_mentioned":142},"This is a Phase I\u002FII study, meaning it will first look at safety and then at how well the treatment works. It is an interventional study, and 32 participants are planned.","completed","Phase I\u002FII Study for Newly-Diagnosed TP53-Mutated AML","This study is testing a combination of two drugs, Bortezomib and CPX-351, for people newly diagnosed with acute myeloid leukemia (AML) that has a specific genetic change called a TP53 mutation. Researchers want to see how safe and effective this combination treatment is. To join, you must be an adult (18 or older) and have not received other chemotherapy for AML. The study will look at how many participants have a complete response (when signs of cancer disappear) over two years and will also determine the highest safe dose of the treatment. The study plans to enroll 32 participants.","The study will measure complete response at 2 years and determine the maximum tolerated dose at 1 year. Other outcomes like overall survival and disease-free survival will be tracked at 1 and 2 years.",99,"Bortezomib will be given under the skin on days 1, 4, 8, and 11. CPX-351 will be given into a vein on days 1, 3, and 5.","Not stated in the trial record.",[33,42],"v2"]