[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06177067":3,"trial-entities:NCT06177067":265,"trial-summary:NCT06177067":277},{"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":22,"study_type":23,"primary_purpose":24,"phases":25,"enrollment_info":27,"interventions":30,"primary_outcomes":72,"secondary_outcomes":77,"sex":89,"minimum_age":90,"maximum_age":91,"healthy_volunteers":15,"eligibility_criteria":92,"std_ages":110,"locations":113,"central_contacts":254,"overall_officials":256,"references":258,"see_also_links":259},"NCT06177067","RAVAML","Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia","A Phase 1 Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia","RECRUITING","2027-04","2026-07","2026-08-03","2024-04-19","St. Jude Children's Research Hospital","OTHER",false,"This is a research study to find out if adding a new study drug called revumenib to commonly used chemotherapy drugs is safe and if they have beneficial effects in treating patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that did not go into remission after treatment (refractory) or has come back after treatment (relapsed), and to determine the total dose of the 3-drug combination of revumenib, azacitidine and venetoclax that can be given safely in participants also taking an anti-fungal drug.\n\nPrimary Objective\n\n* To determine the safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL.\n\nSecondary Objectives\n\n* Describe the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and overall survival for patients treated with revumenib + azacitidine + venetoclax at the recommended phase 2 dose (RP2D).","Patients will receive revumenib + azacitidine + venetoclax in a dose-escalation fashion. The protocol starts at dose level 1. If there are no dose limiting toxicities at dose level 1, then patients will be treated at dose level 2, which equates to the dose of revumenib increasing from 65 to 95 mg\u002Fm\\^2 while the venetoclax exposure remains the same at 21 days. Alternatively, if there are dose limiting toxicities at dose level 1, then the dose level will be deescalated to dose level -1, which equates to the length of exposure of venetoclax being decreased from 21 days to 14 days, while the dose of revumenib stays at 65 mg\u002Fm\\^2. The doses of azacitidine will remain constant at all dose levels.\n\nFor patients whose primary physician considers that single agent revumenib is beneficial (e.g., transition to hematopoietic cell transplant), revumenib can be continued after discussing with study principal investigator. Patients who undergo HCT will be taken off therapy at the time of HCT, but will remain on study. Post-transplant therapy will be determined by the HCT physician.\n\nPatients who do not go on to receive an HCT, may continue to receive revumenib, venetoclax and azacitidine as long as their primary physician considers it beneficial and there are no unacceptable side effects.",[19,20,21],"Refractory Acute Myeloid Leukemia","Relapsed Acute Myeloid Leukemia","Acute Leukemia of Ambiguous Lineage",[],"INTERVENTIONAL","TREATMENT",[26],"PHASE1",{"count":28,"type":29},24,"ESTIMATED",[31,39,45,52,59,66],{"type":32,"name":33,"description":34,"armGroupLabels":35,"otherNames":37},"DRUG","Revumenib","Given by mouth (capsule or liquid solution) or liquid solution by Nasogastric tube (NG) or Gastrostomy tube (G-tube)",[36],"All Eligible Participants",[38],"SNDX-5613",{"type":32,"name":40,"description":41,"armGroupLabels":42,"otherNames":43},"Venetoclax","Given by mouth (tablet) or by NG or G-tube",[36],[44],"Venclextra®",{"type":32,"name":46,"description":47,"armGroupLabels":48,"otherNames":49},"Azacitidine","Given intravenously (IV) infusion",[36],[50,51],"VIDAZA®","5-azacitidine",{"type":32,"name":53,"description":54,"armGroupLabels":55,"otherNames":56},"intrathecal (IT) chemotherapy","Given intrathecal (IT)",[36],[57,58],"ITMHA","methotrexate\u002Fhydrocortisone\u002Fcytarabine",{"type":32,"name":60,"description":61,"armGroupLabels":62,"otherNames":63},"Cytarabine","Given intrathecal (IT) as part of intrathecal (IT) chemotherapy.",[36],[64,65],"Ara-C","Cytosar®",{"type":32,"name":67,"description":61,"armGroupLabels":68,"otherNames":69},"Methotrexate",[36],[70,71],"MTX","Trexall®",[73],{"measure":74,"description":75,"timeFrame":76},"The safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL","The primary endpoint is the recommended phase 2 dose (RP2D) of revumenib + azacitidine + venetoclax.","43 days from the start of therapy.",[78,82,85],{"measure":79,"description":80,"timeFrame":81},"The rates of complete remission (CR)","CR is defined as bone marrow with \\\u003C 5% blasts confirmed by flow cytometry, ANC ≥500\u002FμL and platelets ≥50,000\u002FμL without transfusions, and no evidence of extramedullary disease.","43 days from the start of therapy",{"measure":83,"description":84,"timeFrame":81},"The rates of complete remission with incomplete count recovery (CRi)","CRi is defined as bone marrow with \\\u003C5% blasts confirmed by flow cytometry and ANC \\\u003C500\u002FμL or platelets \\\u003C50,000\u002FμL without transfusions",{"measure":86,"description":87,"timeFrame":88},"The overall survival of patients treated at the RP2D.","Kaplan-Meier estimates with 95% confidence intervals will be used to describe overall survival.","1 year","ALL","1 Year","30 Years",{"inclusion":93,"exclusion":105,"raw_text":109},[94,95,96,97,98,99,100,101,102,103,104],"Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy (one course for secondary AML), or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry.","Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A rearrangement (KAT6Ar), or SET::NUP214","Adequate organ function, defined as total bilirubin \\\u003C 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \\\u003C3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL\u002Fmin\u002F1.73 m\\^2, and left ventricular ejection fraction ≥ 40%","QTcF \\\u003C 480 msec (average of triplicate)","Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.","Lansky ≥ 60 for patients who are \\\u003C 16 years old and Karnofsky ≥ 60% for patients who are \\> 16 years old.","At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg\u002Fm\\^2\u002Fday). In addition, all toxicities must have resolved to grade 1 or less.","Patients must have a leukocyte count \\\u003C25,000 cells\u002FuL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.","For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..","Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.","Patients of reproductive potential must agree to use effective contraception for the duration of study participation.",[106,107,108],"Patients who are pregnant or breastfeeding are not eligible.","Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.","Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible.","Inclusion Criteria: Participants must have a diagnosis of AML or ALAL and meet the criteria below:\n\n* Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy (one course for secondary AML), or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry.\n\nHowever, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.\n\n* Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A rearrangement (KAT6Ar), or SET::NUP214\n* Adequate organ function, defined as total bilirubin \\\u003C 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \\\u003C3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL\u002Fmin\u002F1.73 m\\^2, and left ventricular ejection fraction ≥ 40%\n* QTcF \\\u003C 480 msec (average of triplicate)\n* Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.\n* Lansky ≥ 60 for patients who are \\\u003C 16 years old and Karnofsky ≥ 60% for patients who are \\> 16 years old.\n* At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg\u002Fm\\^2\u002Fday). In addition, all toxicities must have resolved to grade 1 or less.\n* Patients must have a leukocyte count \\\u003C25,000 cells\u002FuL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.\n* For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..\n* Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.\n* Patients of reproductive potential must agree to use effective contraception for the duration of study participation.\n\nPatients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.\n\nExclusion Criteria:\n\n* Patients who are pregnant or breastfeeding are not eligible.\n* Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.\n* Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible.",[111,112],"CHILD","ADULT",[114,131,145,159,173,186,200,214,227,241],{"facility":115,"status":8,"city":116,"state":117,"zip":118,"country":119,"contacts":120,"geoPoint":128},"Rady Children's Hospital","San Diego","California","92132","United States",[121,126],{"name":122,"role":123,"phone":124,"email":125},"Dennis Kuo, MD","CONTACT","858-966-5811","djkuo@rchsd.org",{"name":122,"role":127},"PRINCIPAL_INVESTIGATOR",{"lat":129,"lon":130},32.71571,-117.16472,{"facility":132,"status":8,"city":133,"state":134,"zip":135,"country":119,"contacts":136,"geoPoint":142},"Children's Hospital Colorado","Aurora","Colorado","80045",[137,141],{"name":138,"role":123,"phone":139,"email":140},"Kelly Faulk, MD","720-777-6503","Kelly.Faulk@childrenscolorado.org",{"name":138,"role":127},{"lat":143,"lon":144},39.72943,-104.83192,{"facility":146,"status":8,"city":147,"state":148,"zip":149,"country":119,"contacts":150,"geoPoint":156},"Children's Healthcare of Atlanta","Atlanta","Georgia","30329",[151,155],{"name":152,"role":123,"phone":153,"email":154},"Himalee Sabnis, MD","404-727-3285","hsabnis@emory.edu",{"name":152,"role":127},{"lat":157,"lon":158},33.749,-84.38798,{"facility":160,"status":8,"city":161,"state":162,"zip":163,"country":119,"contacts":164,"geoPoint":170},"Children's Mercy Hospital of Kansas City","Kansas City","Missouri","64108",[165,169],{"name":166,"role":123,"phone":167,"email":168},"Keith August, MD","816-302-6808","kjaugust@cmh.edu",{"name":166,"role":127},{"lat":171,"lon":172},39.09973,-94.57857,{"facility":174,"status":8,"city":175,"state":175,"zip":176,"country":119,"contacts":177,"geoPoint":183},"Memorial Sloan- Kettering Cancer Center","New York","10065",[178,182],{"name":179,"role":123,"phone":180,"email":181},"Maria-Luisa Sulis, MD","212-639-5175","sulism@mskcc.org",{"name":179,"role":127},{"lat":184,"lon":185},40.71427,-74.00597,{"facility":187,"status":8,"city":188,"state":189,"zip":190,"country":119,"contacts":191,"geoPoint":197},"Cincinnati Children's Hospital Medical Center","Cincinnati","Ohio","45229",[192,196],{"name":193,"role":123,"phone":194,"email":195},"Lauren Pommert, MD","513-803-9083","lauren.pommert@cchmc.org",{"name":193,"role":127},{"lat":198,"lon":199},39.12711,-84.51439,{"facility":201,"status":8,"city":202,"state":203,"zip":204,"country":119,"contacts":205,"geoPoint":211},"Children's Hospital of Philadelphia","Philadelphia","Pennsylvania","19104",[206,210],{"name":207,"role":123,"phone":208,"email":209},"Sarah Tasian, MD","267-425-0118","tasians@email.chop.edu",{"name":207,"role":127},{"lat":212,"lon":213},39.95238,-75.16362,{"facility":13,"status":8,"city":215,"state":216,"zip":217,"country":119,"contacts":218,"geoPoint":224},"Memphis","Tennessee","38105",[219,223],{"name":220,"role":123,"phone":221,"email":222},"Hiroto Inaba, MD, PhD","888-226-4343","referralinfo@stjude.org",{"name":220,"role":127},{"lat":225,"lon":226},35.14953,-90.04898,{"facility":228,"status":8,"city":229,"state":230,"zip":231,"country":119,"contacts":232,"geoPoint":238},"UT Southwestern\u002FSimmons Cancer Center","Dallas","Texas","75390",[233,237],{"name":234,"role":123,"phone":235,"email":236},"Kathleen Ludwig, MD","214-456-6927","kathleen.wiertel@utsouthwestern.edu",{"name":234,"role":127},{"lat":239,"lon":240},32.78306,-96.80667,{"facility":242,"status":8,"city":243,"state":230,"zip":244,"country":119,"contacts":245,"geoPoint":251},"Cook Children's Medical Center","Fort Worth","76104",[246,250],{"name":247,"role":123,"phone":248,"email":249},"Holly Pacenta, MD","682-885-4007","Holly.Pacenta@cookchildrens.org",{"name":247,"role":127},{"lat":252,"lon":253},32.72541,-97.32085,[255],{"name":220,"role":123,"phone":221,"email":222},[257],{"name":220,"affiliation":13,"role":127},[],[260,262],{"label":13,"url":261},"http:\u002F\u002Fwww.stjude.org",{"label":263,"url":264},"Clinical Trials Open at St. Jude","http:\u002F\u002Fwww.stjude.org\u002Fprotocols",{"nct_id":4,"conditions":266,"biomarkers":268},[21,267],"Acute Myeloid Leukemia",[269,270,271,272,273,274,275,276],"DEK::NUP214","KAT6A Gene","KMT2A Gene","NPM1 Gene","NUP98 Gene","PICALM::MLLT10","SET::NUP214","UBTF-TD",{"nct_id":4,"found":278,"summary":279,"prompt_version":289},true,{"design":280,"status":281,"heading":282,"summary":283,"follow_up":284,"word_count":285,"commitments":286,"compensation":287,"drugs_mentioned":288},"This is an interventional study with a planned enrollment of 24 participants. It will use a dose-escalation approach to find the safest dose of the drug combination.","completed","Study of Revumenib, Azacitidine, and Venetoclax for Relapsed or Refractory AML\u002FALAL in Children and Young Adults","This research study is looking at whether adding a new drug called revumenib to two commonly used chemotherapy drugs, azacitidine and venetoclax, is safe and effective for children and young adults (ages 1 to 30) with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL). These are types of blood cancer that have either not responded to previous treatments (refractory) or have come back after treatment (relapsed). The main goal is to find the safest dose of this three-drug combination. Revumenib and venetoclax are given by mouth, while azacitidine is given through an IV. Intrathecal (IT) chemotherapy, including cytarabine, may also be given directly into the spinal fluid. The study will measure the safety and tolerability of this combination after 43 days of treatment.","The safety and tolerability of the treatment will be measured at 43 days from the start of therapy. Participants may continue on revumenib, venetoclax, and azacitidine as long as it's beneficial and side effects are manageable, or until hematopoietic cell transplant (HCT).",126,"Participants will receive revumenib, azacitidine, and venetoclax. The specific doses of revumenib and venetoclax may change based on how well participants tolerate the treatment.","Not stated in the trial record.",[33,40,46,53,60],"v2"]