[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"aml-with-gene-mutations\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:aml-with-gene-mutations":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,46],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":32,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":5},"100540176","phase-1-revumenib-in-combination-with-73--midostaurin-in-aml-100540176",false,"NCT06313437","Revumenib in Combination With 7+3 + Midostaurin in AML","A Phase I Trial of Revumenib in Combination With 7+3 (7 Days of Cytarabine and 3 Days of Daunorubicin) + Midostaurin Induction Chemotherapy for the Frontline Treatment of NPM1 and FLT3 Mutated AML","Inclusion Criteria:\n\n* Patients with AML who are newly diagnosed according to the WHO 2022 Classification and previously untreated except for hydroxyurea. ATRA pretreatment for suspected APL for less than 5 days is allowed. Eligible patients with AML arising from an antecedent hematologic disease (AHD) including MDS, may have been treated for their prior hematologic disease (except for allogenic transplant).\n* Patients must be ≥ 18 and \\\u003C 75 years old.\n* Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.\n* Presence of FLT3-ITD and\u002For TKD mutation(s) AND NPM1 mutation in bone marrow or peripheral blood\n* Dose escalation phase only: Presence of any of the following adverse risk genetic characteristics:\n\n  * 2022 ELN adverse risk genetic features:\n\n    * t(6;9)(p23.3;q34.1)\u002FDEK::NUP214\n    * t(v;11q23.3)\u002FKMT2A-rearranged\n    * t(9;22)(q34.1;q11.2)\u002FBCR::ABL1\n    * t(8;16)(p11.2;p13.3)\u002FKAT6A::CREBBP\n    * inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)\u002F GATA2, MECOM(EVI1)\n    * t(3q26.2;v)\u002FMECOM(EVI1)-rearranged\n    * -5 or del(5q); -7; -17\u002Fabn(17p)\n    * Complex karyotype, monosomal karyotype\n    * Mutations in either one of these genes: ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and\u002For ZRSR2\n    * Mutated TP53\n  * NPM1 + FLT3-ITD + DNMT3A mutation\n* LVEF ≥ 50% by MUGA or ECHO at screening.\n* Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL\u002Fmin; determined by the Cockcroft Gault formula.\n* Adequate liver function as demonstrated by:\n\n  * aspartate aminotransferase (AST) ≤ 2.5 × ULN\\*\n  * alanine aminotransferase (ALT) ≤ 2.5× ULN\\*\n  * total bilirubin ≤ 1.5 × ULN\\* \\* Unless considered due to leukemic organ involvement. Note: Subjects with Gilbert's Syndrome may have a total bilirubin \\> 1.5 × ULN per discussion with the Sponsor-Investigator\n* Resolution of adverse reactions to prior drug therapy (such as hydroxyurea) to ≤ grade 1\n* Eligible for intensive cytarabine\u002Fdaunorubicin (7+3) chemotherapy based on the opinion of the treating physician.\n* Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.\n* Females of childbearing potential (i.e., not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum or urine pregnancy test performed within 7 days of day 1.\n* Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged)\n* Consolidation should occur between 1-4 weeks following count recovery after induction and remission (must be confirmed by labs to document maximal response) is established. Subjects will receive medium intensity cytarabine -based consolidation in combination with midostaurin and revumenib if the following criteria are fulfilled.\n\n  * an induction response \\\u003C 5% blasts in the bone marrow and ANC \\>1000 and PLT \\>75000 for whom documented path report is submitted.\n  * sufficiently fit (performance status \\\u003C3)\n  * resolution of any adverse reactions to no greater than grade 1 severity\n\nExclusion Criteria:\n\n* Subject has acute promyelocytic leukemia, inversion (16), t(8;21) AML as described below. Contact Sponsor-Investigator with questions. Inversion 16 and t(8;21): CBF chromosomal abnormalities may be assessed by molecular (PCR), metaphase cytogenetics, or FISH.\n* Subject has known active CNS involvement with AML.\n* Subject has received a strong CYP3A4 inducer (APPENDIX C) within 7 days prior to the initiation of study treatment\n* Strong CYP3A4 inhibitors (APPENDIX C) are contraindicated except strong CYP3A4 inhibitor antifungal azole medications (systemic itraconazole, ketoconazole, posaconazole, voriconazole). For strong CYP3A4 inhibitor antifungal azole medications, the starting dose of revumenib has to be adjusted (Table 1).\n* QTc using Fridericia's correction \\[QTcF\\]) \\> 450 msec. Drugs that prolong QTc should be avoided if possible. A list of common QTc prolonging drugs and alternatives that are not QTc prolonging can be found in APPENDIX D.\n* Subject has tested positive for HIV (due to potential drug-drug interaction between antiretroviral medications and Midostaurin\u002Frevumenib). Note: HIV testing is not required.\n* Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV \\[i.e., HBs Ag-, and antiHBs+\\] are allowed.\n* Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.\n* Subject has a cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.\n* Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his\u002Fher participating in this study.\n* Subject has chronic respiratory disease that requires continuous oxygen use.\n* Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.\n* Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled systemic infection.\n* Subject has a history of other malignancies prior to study entry, with the exception of:\n\n  * Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;\n  * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;\n  * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.\n  * Prior malignancies treated with (surgery+\u002F- chemotherapy+\u002F- radiation) that have remained disease free for at least two years after completion of therapy\n* Subject treated with any form of chemotherapy, immunotherapy, or investigative agent within 1 month of enrollment.\n* Patients who have had prior exposure to a menin inhibitor.","ALL","18 Years","75 Years",{"count":20,"type":21},22,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","This research is being conducted to determine a safe and effective dose of revumenib that can be given in combination with standard induction (initial therapy to induce a remission) + FLT3 targeted therapy (midostaurin) and a single cycle of post-remission therapy + FLT3 targeted therapy (midostaurin) to participants with newly diagnosed Nucleophosmin (NPM1) and FMS-like tyrosine kinase 3 (FLT3) mutated Acute Myeloid Leukemia (AML).\n\nThe names of the study drugs involved in this study are:\n\n* Revumenib (SNDX-5613) (a type of menin inhibitor)\n* Midostaurin (a type of multi-kinase including FLT3 inhibitor)\n* Cytarabine (a type of antineoplastic agent)\n* Daunorubicin (a type of antineoplastic agent)",[27,28,29,30,31],"Acute Myeloid Leukemia","AML, Adult","AML With Gene Mutations","AML","Leukemia",[27,28,33,30,31],"AML with Gene Mutations","RECRUITING","2026-03-23",{"date":37,"type":38},"2026-03-25","ACTUAL",{"date":40,"type":38},"2024-12-06",{"date":42,"type":21},"2028-03-02",{"name":44,"class":45},"Richard Stone, MD","OTHER",{"id":47,"slug":48,"hasResults":11,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":4,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":53,"targetDuration":4,"studyType":22,"phases":55,"briefSummary":56,"conditions":57,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":58,"lastUpdatePostDateStruct":59,"startDateStruct":61,"completionDateStruct":63,"leadSponsor":65,"locationsCount":68},"100544277","phase-1-dose-escalation-and-expansion-study-to-evaluate-the-safety-pk-pd-and-efficacy-of-ze46-0134-in-adults-with-flt3-mutated-or-spliceosome-mutated-relapsed-or-refractory-acute-myeloid-leukemia-100544277","NCT06366789","Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated or Spliceosome Mutated Relapsed or Refractory Acute Myeloid Leukemia","A Phase 1, Open-label, Dose Escalation and Dose Expansion, Multicenter Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ZE46-0134 in Adults With FLT3 Mutated or Spliceosome Mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)","Inclusion Criteria:\n\n1. Written Informed Consent must be obtained from the patient or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).\n2. Patient is ≥18 years of age at the time of obtaining informed consent.\n3. Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).\n4. Group 1: Patient must have a confirmed FLT3-ITD or FLT3-TKD mutation by central laboratory testing. Group 2: Patient must have a documented SF3B1, SRSF2, U2AF1, or ZRSR2 pathogenic mutation by local lab sequencing.\n5. For Group 1 only: Patients must have previously been treated with Gilteritinib with failure to stop disease progression, or not met the criteria for treatment with Gilteritinib in the opinion of the Investigator, or chosen not to have treatment with Gilteritinib for social reasons.\n6. Patients have a life expectancy of at least 3 months in the opinion of the Investigator.\n7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.\n8. Patient must meet the following criteria as indicated on the clinical laboratory tests:\n\n   1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN)\n   2. Serum total bilirubin ≤1.5 × ULN unless due to Gilbert's disease\n   3. Estimated glomerular filtration (eGFR) rate of \\>50 mL\u002Fmin as calculated by the Modification of Diet in Renal Disease equation.\n9. Female patients:\n\n   1. If of non-childbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or\n   2. If of childbearing potential, must:\n\n   i. Have a negative serum pregnancy test at the Screening visit and urine pregnancy test on admission to the clinic on Day-1.\n\n   ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 45 days after the last dose of study drug.\n\n   iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from Screening until at least 45 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle).\n10. Male patients and their female spouse\u002Fpartners who are of childbearing potential must agree to use highly effective contraception consisting of 2 forms of birth control (at least 1of which must be a barrier method) starting at Screening and continue throughout the study period and for 45 days after the final study drug administration. Male patient must not donate sperm starting at Screening and throughout the study period and for 45 days after the final study drug administration.\n\nExclusion Criteria:\n\n1. Written Informed Consent must be obtained from the patient or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).\n2. Patient is ≥18 years of age at the time of obtaining informed consent.\n3. Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).\n4. Patient must have a confirmed FLT3 ITD, TKD or ITD-F691L mutation documented within the past 90 days in absence of therapy or within the Screening period 28 days) prior to study drug administration on C1D1 if therapy has been given.\n5. Patients must have previously been treated with Gilteritinib with failure to stop disease progression, or not met the criteria for treatment with Gilteritinib in the opinion of the Investigator, or chosen not to have treatment with Gilteritinib for social reasons.\n6. Patients have a life expectancy of at least 3 months in the opinion of the Investigator.\n7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.\n8. Patient must meet the following criteria as indicated on the clinical laboratory tests:\n\n   1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN)\n   2. Serum total bilirubin ≤1.5 × ULN unless due to Gilbert's disease\n   3. Estimated glomerular filtration (eGFR) rate of \\>50 mL\u002Fmin as calculated by the Modification of Diet in Renal Disease equation.\n9. Female patients:\n\n   1. If of non-childbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or\n   2. If of childbearing potential, must:\n\n   i. Have a negative serum pregnancy test at the Screening visit and urine pregnancy test on admission to the clinic on Day-1.\n\n   ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 45 days after the last dose of study drug.\n\n   iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from Screening until at least 45 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle).\n10. Male patients and their female spouse\u002Fpartners who are of childbearing potential must agree to use highly effective contraception consisting of 2 forms of birth control (at least 1of which must be a barrier method) starting at Screening and continue throughout the study period and for 45 days after the final study drug administration. Male patient must not donate sperm starting at Screening and throughout the study period and for 45 days after the final study drug administration.\n\nExclusion criteria\n\n1. Diagnosis of isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML)\n2. Acute promyelocytic leukemia (FAB M3)\n3. Active central nervous system (CNS) involvement by AML\n4. Clinical signs\u002Fsymptoms of leukostasis requiring urgent therapy\n5. Known active infection with Human Immunodeficiency Virus (HIV), hepatitis B or hepatitis C. Patients with a history of positive serology for hepatitis B or C require a negative Polymerase chain reaction (PCR) test for virus to go onto therapy\n6. Disseminated intravascular coagulopathy with active, unmanageable bleeding or signs of thrombosis.\n7. Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent; if the half-life of the agent is unknown, patients must wait 1 week prior to first dose of study treatment. An investigational agent is one for which there is no approved indication by the local regulatory authority.\n8. Systemic antineoplastic therapy within 5 half-lives or radiation therapy within 1 week prior to starting protocol with the exception of hydroxyurea, which is allowed to control white blood cell counts.\n9. Female patients who are pregnant or lactating\n10. Patients with psychological, familial, social, or geographic factors, other significant medical condition, laboratory abnormality that otherwise preclude them from giving informed consent, following the protocol, potentially hamper compliance with study treatment and follow-up or would confound the interpretation of the results of the study.\n11. Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction with evidence of residual abnormalities within 6 months prior to enrollment (Troponin (regular or high sensitivity) leak alone not included if no residual dysfunction), New York Heart Association (NYHA) Class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled.\n12. Infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control in the opinion of the Investigator. Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control.",{"count":54,"type":21},150,[24],"This is a clinical study aiming to assess pharmacokinetics, pharmacodynamics and preliminary efficacy of ZE46-0134 in patients with FLT3 and spliceosome mutated Relapsed or Refractory Acute Myeloid Leukemia",[29],"2025-12-24",{"date":60,"type":38},"2025-12-31",{"date":62,"type":38},"2024-05-29",{"date":64,"type":21},"2027-12",{"name":66,"class":67},"Lomond Therapeutics Holdings, Inc.","INDUSTRY",23]