[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"relapsed-adult-aml\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:relapsed-adult-aml":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,9,0,[8,45,72,99,121,146,182,211,236],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":30,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":4},"100636232","phase-2-menin-inhibitor-targeted-maintenance-in-aml-100636232",false,"NCT07563010","Menin-Inhibitor Targeted Maintenance in AML","Phase 2 Randomized Controlled Study of Revumenib as Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With KMT2Ar, NPM1m, or NUP98r Acute Myeloid Leukemia (AML)","Inclusion Criteria:\n\nInclusion Criteria:\n\n1. Aged ≥18 years at the time of signing informed consent\n2. Able to provide written informed consent personally or via a legally authorized representative in accordance with applicable regulatory and institutional requirements\n3. Willing and able to comply with all study procedures and available for the duration of the study\n4. Diagnosis of acute myeloid leukemia (AML) in complete morphologic remission with one of the following molecular abnormalities:\n\n1\\. KMT2A-rearranged (KMT2Ar) AML (Excluding KMT2A partial tandem duplication (KMT2A-PTD) 2. NPM1-mutated (NPM1m) AML (Including FLT3-ITD or TKD co-mutation) 3. NUP98-rearranged (NUP98r) AML 5. Planned first allogeneic hematopoietic cell transplantation (allo-HCT) for AML.\n\n6\\. Transplant Characteristics\n\n1. Planned allo-HCT using bone marrow or peripheral blood stem cell graft source.\n2. Planned reduced-intensity\u002Fnon-myeloablative conditioning (RIC\u002FNMA) or myeloablative conditioning (MAC), using a conditioning regimen permitted- by the protocol and consistent with standard clinical practice, meeting CIBMTR criteria for conditioning intensity\n\n7\\. Planned donor:\n\n1. HLA-matched related donor (5\u002F6 or 6\u002F6)\n2. Matched unrelated donor (8\u002F8)\n3. Mismatched unrelated donor (7\u002F8)\n4. Haploidentical donor meeting institutional requirements\n\n8\\. Performance Status:\n\n1\\. Karnofsky Performance Status ≥70%. 9. Cardiac Function: left ventricular ejection fraction (LVEF) by transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) with no clinical evidence of heart failure: RIC\u002FNMA: ≥50% MAC: ≥5 10. Pulmonary function meeting the following criteria, without supplemental oxygen other than CPAP:\n\n1. RIC\u002FNMA: DLCO (corrected for hemoglobin) and FEV1 ≥40% predicted\n2. MAC: DLCO and FEV1 ≥50% predicted\n\n11\\. Renal Function: estimated creatinine clearance (CrCl) ≥45mL\u002Fmin calculated using the Cockcroft-Gault formula or 24-hour urine collection, consistent with standard eligibility criteria for allogeneic HCT recipients.\n\n12\\. Liver function acceptable per local institutional guidelines for allo-HCT eligibility.\n\n13\\. Reproductive Status: Willingness to use contraception in accordance with local regulations from first study intervention through the required contraceptive period Willingness to use contraception in accordance with local regulations from first study intervention through the required contraceptive period\n\nExclusion Criteria:\n\n1. Disease Status:\n\n   a. Evidence of active AML prior to HCT, assessed within 42 days before transplant, defined as any of the following:\n   * ≥5% bone marrow blasts\n   * Circulating blasts within 14 days before conditioning\n   * CNS or other extramedullary disease\n2. Other active malignancy that, in the investigator's judgment, could interfere with safety or efficacy assessment\n3. Treatment with non-protocol antileukemic therapy (donor lymphocyte infusion for relapse prophylaxis or treatment will be considered an EFS event)\n4. Cardiac \u002F QT Risk\n\n   1. Requirement for concomitant medications known to prolong QT\u002FQTc interval, except low-risk agents used as standard supportive care\n   2. Diagnosis or suspicion of Long QT syndrome, or a family history of Long QT syndrome\n   3. Fridericia's corrected QT interval (QTcF) \\>450 msec.\n   4. History within 6 months of study entry of:\n\n   i. Myocardial infarction ii. Unstable angina iii. Congestive heart failure (NYHA Class ≥ II) iv. Life-threatening or uncontrolled arrhythmia v. Cerebrovascular accident or transient ischemic attack\n5. Chronic respiratory disease requiring continuous supplemental oxygen, or other significant organ dysfunction that would adversely affect study participation.\n6. Active, uncontrolled infection, including any of the following:\n\n   1. Active, uncontrolled systemic fungal, bacterial, or viral infection within 14 days prior to the start of conditioning\n   2. Any other documented active, uncontrolled infection at the start of conditioning\n7. Chronic viral infections with evidence of active disease, including:\n\n   HIV: detectable viral load within 6 months prior to screening\n\n   Hepatitis B:\n   * HBsAg-positive and\u002For anti-HBc-positive with detectable HBV DNA\n   * Anti-HBc-positive alone Hepatitis C: positive HCV antibody with detectable HCV RNA\n8. Planned HCT using cord blood, ex vivo T cell depletion, engineered grafts, or experimental graft sources\n9. Malabsorption syndrome or GI condition that precludes oral administration, including:\n\n   1. Inability to swallow oral medications\n   2. Prior gastric bypass or severe gastroparesis\n   3. Cirrhosis with Child-Pugh Class B or C\n10. Pregnant or breastfeeding\n11. Prior intolerance to menin inhibitor therapy resulting in ≥ Grade 3 treatment-related adverse events\n12. Any condition, therapy, laboratory abnormality, or allergy to excipients that, in the investigator's judgment, could confound study results, interfere with the participant's ability to comply with study procedures or complete the study, or make participation not in the participant's best interest.","ALL","18 Years",{"count":19,"type":20},146,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","Revumenib is a first in class oral menin inhibitor that targets a central oncogenic dependency shared across KMT2Ar, NPM1m, and NUP98r AML. In addition to suppressing leukemogenic transcriptional programs and promoting leukemic differentiation, menin inhibition has been shown to modulate epigenetic states linked to antigen presentation and immune recognition. These properties provide a strong biological rationale for evaluating revumenib as maintenance therapy following alloHCT, with the goal of suppressing residual leukemic clones while preserving or enhancing GVL activity during immune reconstitution.",[26,27,28,29],"Relapsed Adult AML","Stem Cell Transplant Complications","Acute Myeloid Leukemia","Transplant-Related Hematologic Malignancy",[31,32],"Allogenic Transplant","post-transplant relapse prevention","NOT_YET_RECRUITING","2026-06-16",{"date":36,"type":37},"2026-06-22","ACTUAL",{"date":39,"type":20},"2026-12",{"date":41,"type":20},"2031-06",{"name":43,"class":44},"Center for International Blood and Marrow Transplant Research","NETWORK",{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":4,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":52,"targetDuration":4,"studyType":21,"phases":54,"briefSummary":56,"conditions":57,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":71},"100639057","phase-1-adapt-nk-for-high-risk-myeloid-diseases-as-bridge-to-allo-hsct-100639057","NCT07591649","Adapt NK for High Risk Myeloid Diseases as Bridge to Allo HSCT","Safety and Efficacy of Expanded KIR-HLA Mismatched Natural Killer Cell Immunotherapy (AdaptNK) for High-Risk Myeloid Diseases as Bridge to Allogeneic Hematopoietic Stem Cell Transplantation","Inclusion Criteria:\n\n* 18-74 years with Karnofsky score ≥ 70%\n* 75 years and older: KPS ≥ 70%, HCT-CI \\\u003C 5 (excluding history of solid tumor), AND not frail by Fried frailty criteria (see Appendix III)\n* HLA type C1\u002FC1 or C2\u002FC2\n\nNote: For easy determination, the definition of HLA-C ligand group assigments is included below:\n\nHLA-C1 group alleles are defined as HLA-C01, C03, C07, C08, C12, C14, C16 HLA-C2 group alleles are defined as HLA-C02, C04, C05, C06, C15, C17, C18\n\n* adequate liver, renal, pulmonary and cardiac function\n* ability to be off glucocorticoids and other immunosuppressive medications indicated for acute or chronic GVHD for at least 28 days prior to the AdaptNK cell infusion\n* There must be sufficient time between the most recent therapy and the screening bone marrow as delineated below:\n* anti-leukemic systemic cytotoxic chemotherapy - 2 weeks\n* Targeted anti-leukemic agents (FLT-3, IDH, menin inhibitors) - 3 half-lives of the medication\n* Radiotherapy - 1 week\n* donor lymphocyte infusions - 6 weeks\n* hematopoietic growth factors (filgrastim, TPO agonists, EPO) - 1 week\n* biologic therapy (monoclonal antibodies, T-cell engagers) - 2 weeks\n* Immune effector cellular therapy - 4 weeks\n* Intrathecal chemotherapy for treatment of active CNS leukemia - there must be at least two CSF samples negative for leukemia separated by one week before enrollment.\n* WBC shall be \\\u003C 25,000 before infusion. Hydroxyurea is permitted until day -3 to control excess blast proliferation. No other systemic treatment is allowed after the screening bone marrow is performed for inclusion in protocol\n* All prior treatment related toxicities should have resolved to ≤ grade 1 prior to study enrollment\n* agrees to use of adequate contraception from study enrollment to 4 months after cell infusion\n* voluntary written consent\n\nExclusion Criteria:\n\n* Myeloid neoplasms with known or strongly suspected germline background, except DDX41, TP53, or RUNX1.\n* Acute promyelocytic leukemia (APL)\n* myocardial infarction (MI) within previous 6 months of study enrollment\n* pregnant or breastfeeding\n* Active CNS involvement with AML\n* new or progressive pulmonary infiltrates\n* active autoimmune disease requiring immunosuppressive therapy\n* Preexisting inflammatory disease requiring immunosuppressive therapy\n* history of severe asthma and currently on chronic systemic medications\n* HIV-1\u002F2 positivity or hepatitis C\u002FB\n* active systemic infections requiring anti-infective treatment\n* received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)\n* Patients with second malignancies are excluded if they have required systemic cytotoxic chemotherapy within 1 year or if they are not in remission\n* Exception: patients that are on stable dosing of hormonal therapy (e.g. aromatase inhibitor or antiandrogen therapy) for active breast or prostate cancer for 1 year are eligible.\n* Patients with excised basal cell or squamous cell carcinoma of the skin are eligible.\n* Patients with excised carcinoma in situ of the cervix or breast are eligible.\n* Patients with untreated T1a or T1b prostate cancer are eligible.",{"count":53,"type":20},18,[55,23],"PHASE1","This is a multi-institutional Phase I\u002FII study of an allogeneic KIR-HLA mismatched NK cell infusion (AdaptNK) and a short course of subcutaneous interleukin-2 (IL-2) administered after lymphodepleting chemotherapy \\[cyclophosphamide (CY)\u002Ffludarabine (FLU)\\] in patients with relapsed or refractory acute myelogenous leukemia (AML). AdaptNK is a natural killer (NK) cell product that is enriched for NK cells with an \"adaptive\", or human cytomegalovirus (CMV)-induced, phenotype.",[26,58,59],"Refractory AML","Acute Myelogenous Leukemia","RECRUITING","2026-05-15",{"date":63,"type":37},"2026-05-19",{"date":65,"type":37},"2026-05-08",{"date":67,"type":20},"2035-03-01",{"name":69,"class":70},"Masonic Cancer Center, University of Minnesota","OTHER",1,{"id":73,"slug":74,"hasResults":11,"nctId":75,"briefTitle":76,"officialTitle":77,"acronym":78,"eligibilityCriteria":79,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":80,"targetDuration":4,"studyType":21,"phases":82,"briefSummary":83,"conditions":84,"keywords":85,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":93,"completionDateStruct":95,"leadSponsor":97,"locationsCount":71},"100565980","phase-1-study-investigating-the-safety-of-cd19-car-t-cells-in-relapsedrefractory-aml-expressing-cd19-100565980","NCT06649227","Study Investigating the Safety of CD19 CAR-T Cells in Relapsed\u002FRefractory AML Expressing CD19","Prospective Non-randomized Phase I Study Investigating the Safety of CD19 CAR-T Cells in Patients With Refractory\u002FRelapsed AML Expressing CD19.","CARLA-M19","Inclusion Criteria:\n\n* Subject is ≥ 18 years of age at the time of signing the informed consent form,\n* Patient with AML that expresses CD19 by Flow-cytometry, (CD19 expression ≥ 70% of AML blasts)\n* Patients with R\u002FR AML defined as:\n\n  * Primary refractory: absence of remission after two courses of induction chemotherapy,\n  * Secondary refractory: absence of remission after salvage treatment in relapsing patients,\n  * Post-transplant relapse in patients having had allo-HCT.\n* Lack of accessible targeted therapy that has not been previously utilized.\n* Eastern Cooperative Oncology Group (ECOG) performance status of \\\u003C 2,\n* Estimated life expectancy of \\> 2 months,\n* Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (CNS) involvement,\n* Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia),\n* Platelet count ≥ 30000\u002FuL,\n* Absolute lymphocyte count ≥ 200\u002FuL,\n* Creatinine clearance (as estimated by Cockcroft Gault) ≥ 40 mL\u002Fmin,\n* Serum ALT\u002FAST ≤ 2.5 upper limit of normal (ULN),\n* Total bilirubin ≤ 1.5 mg\u002Fdl, except in subjects with Gilbert's syndrome,\n* Cardiac ejection fraction ≥ 45 %,\n* No clinically significant electrocardiogram (ECG) findings,\n* No clinically significant pleural effusion,\n* Baseline oxygen saturation \\> 92 % on room air,\n* Female patients of childbearing potential must:\n\n  1. have a negative pregnancy test (blood) at screening visit.\n  2. either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption, from screening through 1 year following the CAR-T cell infusion. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) must be practiced. The patient should be informed of the potential risks associated with becoming pregnant while enrolled in this clinical trial. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \\[e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal\\] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled.\n  3. Agree to abstain from breast feeding during the study participation and for 1 year after the CAR-T cell infusion.\n* Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after the CAR-T cell infusion, even if he has undergone a successful vasectomy.\n\nExclusion Criteria:\n\n* Patient unable to sign the informed consent,\n* Patient with R\u002FR AML that does not expresses CD19,\n* History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease-free and without anticancer therapy for at least 3 years,\n* Prior CD19 targeted therapy,\n* Prior CAR therapy or other genetically modified T cell therapy,\n* Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management,\n* History of human immunodeficiency virus (HIV) or HTLV1,\n* Infection or acute or chronic active hepatitis C infection,\n* Infection or acute or chronic active hepatitis (Hep) B. Subjects with history of Hep B or Hep C infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines,\n* Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid (CSF) malignant cells or brain metastases,\n* History or presence of non-malignant CNS disorder, such as seizure disorder, cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement,\n* Patient placed under guardianship or curatorship,\n* Females either pregnant\u002Fbreast-feeding or planning to become pregnant,\n* Any contraindication due to hypersensitivity to the active substance or to any of the excipients,\n* Contraindication to the lymphodepleting chemotherapy,\n* Absence of medical insurance cover.",{"count":81,"type":20},5,[55],"Refractory\u002FRelapsed (R\u002FR) acute myeloid leukemia (AML) is associated with a dis-mal prognosis.\n\nIn some subsets of AML such as AML driven by the t(8;21) translocation, leading to the RUNX1-RUNX1T1 (AML1-ETO) fusion transcript expression, CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 % of cases. Interestingly, the expression of the CD19 antigen is also detected in the CD34+ CD38-population leukemic stem cells.\n\nt(8;21) AML subtype has a rather good prognosis with an intensive chemotherapy regimen, but relapses occur in around 40 % of the patients and new therapeutic options are needed for these patients.\n\nPlesa et al, reported a successful treatment of a refractory t(8;21) AML with bispecific monoclonal antibodies that targets CD19. More recently, Danylesko et al, have reported long-term remission following CD19 CAR-T cells in a heavily pre-treated patient with t(8;21) AML(1). The same group has just submitted an abstract of 6 treated patients to the European Haematology Association (EHA) 2023 meet-ing: Six patients (adults-5, child-1) with t(8; 21) AML (confirmed by cytogenetic and FISH) and aberrant CD19 expression were included. One patient had a complex karyotype. Molecular analysis for CKIT, NPM1, IDH1, IDH2, and CBPa were nega-tive in all pts. One pt harbors the FLT3 ITD and TKD mutations. Median number of previous chemotherapy (CT) lines was 4 (3-8). Four patients were with chemo re-sistant relapse post allo-HCT (MSD-1, 10\u002F10 MUD -3) 5-18 months before CAR T-cell infusion. All patients developed CRS (grade 1-3) and were treated with i.v tocili-zumab and dexamethasone. 2\u002F6 patients suffered from ICANS and were treated with steroids. In 4\u002F6 patients, day 28 BM aspiration disclosed normal hematopoie-sis with no excess blasts and lack of t(8;21) by FISH confirming clinical and cyto-genetic remission, while 2\u002F6 pts with progressive AML had no response (Danylesko etal. Abstract EHA 2023, submitted).\n\nInterestingly, other subsets of AML display an aberrant expression of CD19. These observations indicate that CD19 can be a target of choice for CAR-T cells in patients with R\u002FR AML expressing this antigen.\n\nIn this study, we plan to offer anti-CD19 CAR-T cell therapy to patients with re-lapsed\u002Frefractory AML expressing CD19 for whom no curative alternatives are available.\n\nTo this end, CAR-T cells will be manufactured using closed semi-automated bioreactor CliniMACS Prodigy (Miltenyi Biotec) in academic setting.",[26],[86,87,88,89],"Relapsed\u002Frefractory AML expressing CD19","AML","CD19","CAR-T cells","2025-11-27",{"date":92,"type":37},"2025-12-05",{"date":94,"type":37},"2025-07-10",{"date":96,"type":20},"2030-07-10",{"name":98,"class":70},"University Hospital, Lille",{"id":100,"slug":101,"hasResults":11,"nctId":102,"briefTitle":103,"officialTitle":104,"acronym":4,"eligibilityCriteria":105,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":106,"enrollmentInfo":107,"targetDuration":4,"studyType":21,"phases":109,"briefSummary":110,"conditions":111,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":112,"lastUpdatePostDateStruct":113,"startDateStruct":115,"completionDateStruct":117,"leadSponsor":119,"locationsCount":71},"100539685","phase-1-cll-1-car-nk-cells-for-relapsedrefractory-aml-100539685","NCT06307054","CLL-1 CAR-NK Cells for Relapsed\u002FRefractory AML","The Safety and Efficacy for Anti-human CLL-1 CAR-NK Cells in Subjects With Relapsed\u002FRefractory Acute Myeloid Leukemia","Inclusion Criteria:\n\n1. Age 18-70 years, gender unrestricted;\n2. Expected survival time exceeds 12 weeks;\n3. ECOG score 0-2;\n4. Meets the 2022 WHO criteria for acute myeloid leukemia and flow cytometry shows ≥70% expression of CLL1 in leukemia cells; or immunohistochemistry shows CLL1 expression ≥50% and meets the following criteria for relapse and refractory:\n\n   1. Relapse criteria: Bone marrow shows primitive cells ≥5% after hematological remission (excluding post-chemotherapy hematopoietic recovery); or at least two peripheral blood samples taken at least one week apart show primitive cells; or extramedullary lesions are present. Early relapse (relapse within 12 months after initial remission) patients can be directly included, while late relapse (relapse after 12 months of initial remission) patients must have undergone salvage chemotherapy according to standard protocols without achieving complete remission. Salvage treatment for all relapsed patients should include at least one course of targeted therapy without achieving remission. Patients who relapse after allogeneic hematopoietic stem cell transplantation, have no other effective treatment options, and have no active grade 2 or higher acute GVHD.\n   2. Refractory criteria: No complete remission after two courses of standard intensive chemotherapy based on the 3+7 regimen, and no complete remission after second-line salvage chemotherapy or treatment including targeted therapy; or no complete remission after one course of purine analog induction chemotherapy (such as FLAG-Ida, CLIA, or similar regimens), and no complete remission after salvage treatment or treatment including targeted therapy; or no complete remission after three cycles of low-intensity treatment based on HMA, including low-intensity regimens containing venetoclax; relapse within 12 months after remission (early relapse); patients for whom the original induction is ineffective after relapse.\n5. Able to establish the required venous access for collection, and no contraindications for leukapheresis;\n6. Liver and kidney function, cardiac and pulmonary function meet the following requirements:\n\n   1. Creatinine clearance (calculated by Cockcroft-Gault formula) ≥ 60 mL\u002Fmin or creatinine ≤ 2.5×ULN;\n   2. Ejection fraction \\>50%, no clinically significant electrocardiogram changes; baseline blood oxygen saturation \\>92%; total bilirubin ≤ 3×ULN; ALT and AST ≤ 3×ULN;\n7. Able to understand and sign the informed consent form.\n\nExclusion Criteria:\n\nAny of the following conditions disqualify a subject from participation in the trial:\n\n1. Confirmed AML with PML-RARA fusion gene;\n2. History of malignancies other than acute myeloid leukemia within 5 years before screening, except adequately treated carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin, or prostate cancer after radical surgery, or thyroid cancer after radical surgery;\n3. Uncontrolled active bacterial, viral, or fungal infections requiring treatment; HBsAg or HBcAb positive, with peripheral blood HBV DNA ≥ lower limit of detection; HCV RNA positive in the presence of hepatitis C virus antibodies; positive TRUST test for syphilis; HIV antibody positive;\n4. Significant organ (cardiovascular, pulmonary) dysfunction; active gastrointestinal bleeding within the past 3 months; uncontrolled hypertension or history of hypertensive crisis or hypertensive encephalopathy; significant history or evidence of major cardiovascular risk, including congestive heart failure, unstable angina, clinically significant arrhythmias (such as ventricular fibrillation, ventricular tachycardia, etc.); history of arterial thrombosis within the past 3 months (such as stroke, transient ischemic attack); symptomatic deep vein thrombosis within the past 6 months, history of pulmonary embolism, or history of coronary angioplasty, defibrillation, or any clinical significant complications or diseases that may pose a risk to the subject's safety or interfere with the study evaluation, procedures, or completion;\n5. Any uncontrolled active disease that hinders participation in the trial;\n6. Active, uncontrolled central nervous system involvement, or a history of central nervous system disease requiring treatment (such as epilepsy);\n7. Subjects receiving systemic corticosteroid therapy before screening and deemed by the investigator to require long-term systemic corticosteroid therapy during the study period (excluding inhalation or local use); and subjects who have received systemic corticosteroid therapy within 72 hours before cell infusion (excluding inhalation or local use);\n8. Subjects who have used PD-1 or PD-L1 monoclonal antibodies within 3 months before enrollment\n9. Pregnant or lactating women; and subjects planning to become pregnant within 1 year after infusion, during or after the treatment period;\n10. Uncontrolled active infections (excluding simple urinary tract infections or upper respiratory tract infections);\n11. Subjects who have received CAR-T therapy or other gene-modified cell therapy in the past;\n12. Patients after allogeneic transplantation, with no significant acute or chronic GVHD, and have discontinued immunosuppressive drugs for at least 1 month;\n13. Known allergy to any component of anti-CLL-1 CAR-NK cell infusion or chemotherapy regimen (cyclophosphamide and fludarabine);\n14. Any situation deemed by the investigator to compromise the safety of the subject or interfere with the purpose of the study, or deemed unsuitable for participation by the investigator;\n15. Afflicted with a condition that affects the ability to sign the informed consent form in writing or to comply with the study procedures; unwilling or unable to comply with the study requirements.","70 Years",{"count":108,"type":20},24,[55],"This study is a single-arm, open-label, dose-escalation clinical trial aimed at exploring the safety, tolerability, and pharmacokinetic characteristics of the CLL-1 CAR NK cells, as well as providing preliminary observations on its efficacy in subjects with relapsed\u002Frefractory acute myeloid leukemia.",[26,58],"2025-09-28",{"date":114,"type":37},"2025-09-30",{"date":116,"type":37},"2024-04-01",{"date":118,"type":20},"2027-03-15",{"name":120,"class":70},"Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine",{"id":122,"slug":123,"hasResults":11,"nctId":124,"briefTitle":125,"officialTitle":126,"acronym":4,"eligibilityCriteria":127,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":128,"targetDuration":4,"studyType":21,"phases":130,"briefSummary":131,"conditions":132,"keywords":135,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":137,"lastUpdatePostDateStruct":138,"startDateStruct":140,"completionDateStruct":142,"leadSponsor":144,"locationsCount":71},"100462759","phase-2-venetoclax-combining-chidamide-and-azacitidine-vca-in-the-treatment-of-rr-aml-100462759","NCT05305859","Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of R\u002FR AML","A Multi-center, Prospective, Single-arm Study of Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of Refractory\u002FRelapsed Acute Myelogenous Leukemia (R\u002FR AML)","Inclusion Criteria:\n\n* Age ≥18\n* Relapsed and refractory patients with acute myeloid leukemia via morphology and immunology\n* ECOG：0-2\n* Life expectancy ≥ 3 months\n* Adequate laboratory parameters during the screening period as evidenced by the following:\n\n  1. Creatinine clearance≥30 mL\u002Fmin and serum Creatinine ≤ 160µmol\u002FL\n  2. ALT and AST ≤ 3 × upper limit of normal (ULN)\n  3. Able to understand and sign an informed consent form (ICF).\n\nExclusion Criteria:\n\n* Diagnosis of acute promyelocytic leukemia (APL)\n* Central nervous system leukemia\n* Uncontrolled or significant cardiovascular disease, including any of the following:\n\n  1. Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker; Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);\n  2. Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg; History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);\n  3. History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);\n  4. History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening;\n  5. History of New York Heart Association Class 3 or 4 heart failure;\n  6. Complete left bundle branch block;\n  7. Known history of left ventricular ejection fraction (LVEF) ≤45% or less than the institutional lower limit of normal;\n* Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;\n* Suffered from other non-myeloid malignancies within 2 years, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease\n* Females who are pregnant or breastfeeding;\n* Mental disorders that hinder research participation\n* Previous solid organ transplantation (SCT treatment is allowed in advance, but if the patient has GVHD or is still receiving immunosuppression\u002FGVHD treatment, it is not allowed)\n* Any other situation where the investigator believes that the patient should not participate in this trial",{"count":129,"type":20},30,[23],"The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of relapsed and\u002For refractory AML",[133,26,134],"Leukemia, Myeloid, Acute","Refractory Leukemia",[136],"refractory\u002Frelapsed acute myelogenous leukemia","2025-09-04",{"date":139,"type":37},"2025-09-11",{"date":141,"type":37},"2022-01-12",{"date":143,"type":20},"2027-06-30",{"name":145,"class":70},"The First Affiliated Hospital of Xiamen University",{"id":147,"slug":148,"hasResults":11,"nctId":149,"briefTitle":150,"officialTitle":151,"acronym":152,"eligibilityCriteria":153,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":154,"targetDuration":4,"studyType":21,"phases":156,"briefSummary":157,"conditions":158,"keywords":161,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":171,"lastUpdatePostDateStruct":172,"startDateStruct":174,"completionDateStruct":176,"leadSponsor":178,"locationsCount":181},"100351035","phase-1-clinical-trial-to-evaluate-the-safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-tuspetinib-hm43239-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-100351035","NCT03850574","Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia","A Phase 1\u002F2 Open Label, Multicenter, Dose Escalation and Expansion Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM43239 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)","TUSCANY","Inclusion Criteria for Parts A\u002FB\u002FC:\n\n* Study participant is defined as having morphologically documented primary or secondary AML, MDS-IB2 (≥ 10% bone marrow blasts), or CMML by the World Health Organization (WHO) criteria (2016), and fulfills one of the following:\n\n  1. Refractory to at least 1 cycle of prior therapy\n  2. Relapsed after achieving remission with a prior therapy\n* Study participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.\n* Study participant's interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), at 4 weeks for biologic or cellular immunotherapies, or least 5 half-lives for prior experimental agents or noncytotoxic agents, including immunosuppressive therapy post hematopoietic stem cell transplantation (HSCT). Upon discussion with the Medical Monitor, a shorter than stated washout period may be considered provided that the study participant has recovered from any clinically relevant safety issue and recovered to Grade ≤ 1 toxicity from prior therapies.\n* Study participant must meet the following criteria as indicated on the clinical laboratory tests.\n\n  1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× institutional upper limit normal (ULN)\n  2. Total serum bilirubin ≤ 1.5× institutional ULN\n  3. Creatinine clearance as calculated by the Cockcroft-Gault formula or measured by 24-h urine collection of \\> 45 mL\u002Fmin.\n* Study participant is suitable for oral administration of study drug and has minimum life expectancy (≥ 3 months)\n* Female study participants must be either:\n* Of non-childbearing potential\n\n  1. Post-menopausal (defined as at least 1 year without any menses) prior to screening, or\n  2. Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)\n* Or, if of childbearing potential,\n\n  1. Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and\n  2. Must use an acceptable highly effective method of birth control starting at screening and throughout the study period and for 90 days after the final study drug administration.\n* Female study participants must not be breastfeeding at screening and during the study period, and for 90 days after the final study drug administration\n* Female study participants must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration.\n* Male study participants and their female spouse\u002Fpartners who are of childbearing potential must be using highly effective contraception starting at screening and continue throughout the study period and for 90 days after the final study drug administration.\n* Male study participants must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.\n* Study participant agrees not to participate in another interventional study while on treatment.\n\nExclusion Criteria for Parts A\u002FB\u002FC:\n\nStudy participants must not enter the study if any of the following exclusion criteria are met:\n\n* Study participant was diagnosed with acute promyelocytic leukemia (APL).\n* Study participant has known BCR-ABL-positive leukemia.\n* Study participant has an active malignancy other than AML, MDS-IB2, or CMML.\n* Study participant has persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4.03), with symptoms and objective findings, from prior AML, MDS-IB2, or CMML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery)\n* Study participant has had hematopoietic stem cell transplant (HSCT) and meets any of the following criteria:\n\n  1. Has undergone HSCT within the 2-month period prior to the first study dose\n  2. Has clinically significant graft-versus-host-disease (GVHD) requiring treatment\n  3. Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant\n  4. Had a donor lymphocyte infusion (DLI) ≤ 30 days prior to the first study dose.\n* Study participant has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy.\n* Study participant has disseminated intravascular coagulation abnormality (DIC).\n* Study participant has had major surgery within 4 weeks prior to the first study dose.\n* Study participant has had radiation therapy within 4 weeks prior to the first study dose.\n* Study participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or study participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.\n* Study participant has any of the following cardiac abnormalities of history:\n\n  1. Study participant has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval \\> 250 milliseconds (ms).\n  2. Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) \\> 450 ms in three successive screening measurements.\n  3. Study participant has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT, syndrome, family history of long QT syndrome.\n* Study participant is known to have active infection including any identified active COVID-19 infection.\n* Study participant is known to have human immunodeficiency virus infection.\n* Study participant has known active hepatitis B or C, or other active hepatic disorder.\n* Study participant has any condition which, in the Investigator's opinion, makes the study participant unsuitable for study participation.\n* Study participant has a history of Grade 3 or 4 non-hematologic toxicity related to tyrosine kinase inhibitor.\n\nInclusion Criteria for Part D:\n\n* Study participant is defined as having morphologically documented newly diagnosed previously untreated primary or secondary AML by the World Health Organization (WHO) criteria (2016) and considered ineligible to receive intensive chemotherapy.\n\nStudy participants ≥ 75 years of age are considered ineligible to receive intensive chemotherapy if they meet any of the following criteria:\n\n1. ECOG Performance Status of 2 or 3;\n2. Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina;\n3. Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume during the first second (FEV1) ≤ 65%;\n4. Creatinine clearance ≥ 30 mL\u002Fmin to \\\u003C 45 ml\u002Fmin;\n5. Moderate hepatic impairment with total bilirubin \\> 1.5 to ≤ 3.0×ULN;\n6. Any other comorbidity that the Investigator judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and prior to treatment.\n\nStudy participants are considered ineligible to receive intensive chemotherapy based on their age being ≥ 75 years.\n\n* Study participant \\\u003C 75 years has an ECOG performance status ≤ 2; study participant ≥ 75 years has an ECOG performance status 0-2.\n* Study participant must meet the following criteria as indicated on the clinical laboratory tests:\n\n  1. Serum AST and ALT ≤ 3× institutional ULN unless considered due to leukemic organ involvement.\n  2. Total serum bilirubin ≤ 3x institutional ULN unless considered due to leukemic organ involvement for study participants \\\u003C 75 years; total serum bilirubin ≤ 1.5x institutional ULN (or ≤ 3x institutional ULN if documented history of Gilbert's syndrome) unless considered due to leukemic organ involvement for study participants ≥ 75 years.\n  3. Creatinine clearance as calculated by the Cockcroft-Gault formula or measured by 24-h urine collection of ≥ 30 mL\u002Fmin for study participants \\\u003C 75 years; creatinine clearance as calculated by the Cockcroft-Gault formula or measured by 24-h urine collection of ≥ 45 mL\u002Fmin for study participants ≥ 75 years.\n* Study participant is suitable for oral administration of study drug and has minimum life expectancy (≥ 3 months)\n* Female study participants must be either:\n* Of non-childbearing potential\n\n  1. Post-menopausal (defined as at least 1 year without any menses) prior to screening, or\n  2. Documented surgically sterile or status post hysterectomy (at least 1 month prior to screening)\n* Or, if of childbearing potential,\n\n  1. Must have a negative serum or urine pregnancy test at screening (within 72 hours prior to start of treatment), and\n  2. Must use an acceptable highly effective contraception starting at screening and throughout the study period and for 90 days after the final study drug administration.\n* Female study participants must not be breastfeeding at screening and during the study period, and for 90 days after the final study drug administration.\n* Female study participants must not donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration.\n* Male study participants and their female spouse\u002Fpartners who are of childbearing potential must be using highly effective contraception starting at screening and continue throughout the study period and for 90 days after the final study drug administration.\n* Male study participants must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.\n* Study participant agrees not to participate in another interventional study while on treatment.\n\nExclusion Criteria for Part D:\n\nStudy participants must not enter the study if any of the following exclusion criteria are met:\n\n* Study participant was diagnosed with acute promyelocytic leukemia (APL).\n* Study participant has known BCR-ABL-positive leukemia.\n* Study participant has an active malignancy other than AML.\n* Study participant has received treatment with the following:\n\n  1. An HMA, VEN (or other BCL-2 inhibitor), a tyrosine kinase inhibitor (TKI), a FLT3 inhibitor (FLT3i), a hematopoietic stem cell transplant (HSCT), and\u002For a chemotherapeutic agent for antecedent myeloid neoplasm (Note: Prior chemotherapy for solid tumors considered in remission is allowed.)\n  2. CAR-T cell therapy\n  3. Experimental therapies for antecedent myeloid neoplasms\n  4. Current participation in another research or observational study\n* Study participant has persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4.03), with symptoms and objective findings, from treatment for antecedent myeloid neoplasms (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, immunosuppressive therapy, radiation, or surgery).\n* Study participant has meningeal or central nervous system (CNS) involvement with leukemia or other CNS disease related to underlying and secondary effects of malignancy.\n* Study participant has disseminated intravascular coagulation abnormality (DIC).\n* Study participant has had major surgery within 4 weeks prior to the first study dose.\n* Study participant has had radiation therapy within 4 weeks prior to the first study dose.\n* Study participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or study participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.\n* Study participant has any of the following cardiac abnormalities of history:\n\n  1. Study participant has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval \\> 250 milliseconds (ms).\n  2. Study participant has a mean QT interval (QTc) by Friderica's method (QTcF) \\> 450 ms in three successive screening measurements.\n  3. Study participant has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT, syndrome, family history of long QT syndrome.\n* Study participant is known to have active infection, including any identified active COVID-19 infection.\n* Study participant is known to have human immunodeficiency virus infection.\n* Study participant has known active hepatitis B or C, or other active hepatic disorder.\n* Study participant has any condition which, in the Investigator's opinion, makes the study participant unsuitable for study participation, including a chronic respiratory disease that requires continuous oxygen, or a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, or cardiovascular disease, or any other medical condition or known hypersensitivity to any of the study medications including excipients of VEN and AZA that in the opinion of the Investigator would adversely affect participating in this study.\n* Study participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal) or other medical conditions (e.g., infection, heart failure, COPD flare, etc.).\n* Study participant has a white blood cell count \\> 25 × 10\\^9\u002FL. (Treatment with hydroxyurea or use of leukapheresis are permitted to meet this criterion.)",{"count":155,"type":20},240,[55,23],"The main purpose of this study is to identify a safe and potentially effective dose of tuspetinib to be used in future studies in study participants diagnosed with acute myeloid leukemia (AML), myelodysplastic syndromes with increased blasts grade 2 (MDS-IB2), or chronic myelomonocytic leukemia (CMML) that is relapsed or refractory after at least one line of prior therapy, or in study participants with newly diagnosed AML. Tuspetinib will be administered as a single agent or in combination with other drugs (venetoclax or venetoclax plus azacitidine), as specified for each part of the study.",[133,58,26,159,160],"Myelodysplastic Syndrome With Excess Blasts-2","Chronic Myelomonocytic Leukemia",[162,28,87,163,164,165,166,160,167,168,169,170],"Tuspetinib","Relapsed","Refractory","Myelodysplastic Syndromes with Increased Blasts Grade 2","MDS-IB2","CMML","Venetoclax","Azacitidine","Newly Diagnosed","2025-08-20",{"date":173,"type":37},"2025-08-26",{"date":175,"type":37},"2019-03-11",{"date":177,"type":20},"2027-04",{"name":179,"class":180},"Aptose Biosciences Inc.","INDUSTRY",34,{"id":183,"slug":184,"hasResults":11,"nctId":185,"briefTitle":186,"officialTitle":186,"acronym":187,"eligibilityCriteria":188,"healthyVolunteers":189,"sex":16,"minAge":17,"maxAge":190,"enrollmentInfo":191,"targetDuration":4,"studyType":21,"phases":193,"briefSummary":195,"conditions":196,"keywords":199,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":201,"lastUpdatePostDateStruct":202,"startDateStruct":204,"completionDateStruct":206,"leadSponsor":208,"locationsCount":210},"100457489","specialty-compared-to-oncology-delivered-palliative-care-for-patients-with-acute-myeloid-leukemia-100457489","NCT05237258","Specialty Compared to Oncology Delivered Palliative Care for Patients With Acute Myeloid Leukemia","SCOPE-L","Inclusion Criteria:\n\n* Patient Inclusion Criteria\n\n  * Hospitalized patients (age ≥ 18 years) with high-risk AML defined as:\n  * Patients with new diagnosis ≥ 60 years of age\n  * An antecedent hematologic disorder\n  * Therapy related-disease\n  * Relapsed or primary refractory AML\n  * Within five business days of initiating therapy with either a) intensive chemotherapy (7+3) or modification of this regimen on a clinical trial, or a similar intensive regimen requiring prolonged hospitalization; or b) hypomethylating agents +\u002F- additional agents or modification of this regimen on a clinical trial.\n* Caregiver Inclusion Criteria\n\n  * Adult (≥18 years) relative or friend of a participating patient who the patient identifies as living with or has in-person contact with them at least twice per week.\n\nExclusion Criteria:\n\n\\- Patient Exclusion Criteria\n\n* Patients with a diagnosis of acute promyelocytic leukemia (APML)\n* Patients with AML receiving supportive care alone\n* Patients with psychiatric or cognitive conditions which the treating clinicians believe prohibits informed consent or compliance with study procedures\n* Patients seen by a palliative care clinician (MD, DO, APP) during two previous hospitalizations in the six months prior to enrollment\n* Patients expected to be discharged within 2 days",true,"120 Years",{"count":192,"type":20},2300,[194],"NA","This research study is evaluating whether primary palliative care is an alternative strategy to specialty palliative care for improving quality of life, symptoms, mood, coping, and end of life outcomes in patients with acute myeloid leukemia (AML).",[26,197,198],"Primary Refractory Acute Myeloid Leukemia","High Risk Acute Myeloid Leukemia",[26,197,198,200],"Caregivers","2025-07-22",{"date":203,"type":37},"2025-07-25",{"date":205,"type":37},"2022-06-01",{"date":207,"type":20},"2029-04",{"name":209,"class":70},"Massachusetts General Hospital",20,{"id":212,"slug":213,"hasResults":11,"nctId":214,"briefTitle":215,"officialTitle":216,"acronym":217,"eligibilityCriteria":218,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":219,"targetDuration":4,"studyType":21,"phases":221,"briefSummary":222,"conditions":223,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":227,"lastUpdatePostDateStruct":228,"startDateStruct":230,"completionDateStruct":232,"leadSponsor":234,"locationsCount":210},"100517781","phase-2-study-investigating-the-efficacy-and-safety-of-the-addition-of-oral-azacitidine-to-salvage-treatment-by-gilteritinib-in-subjects-18-years-of-age-with-relapsedrefractory-flt3-mutated-acute-myeloid-leukemia-100517781","NCT06022003","Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed\u002FRefractory FLT3-mutated Acute Myeloid Leukemia","Open-label, Phase 2 Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed\u002FRefractory FLT3-mutated Acute Myeloid Leukemia","OGILAR","Inclusion Criteria:\n\n1. Confirmed diagnosis of acute myeloid leukemia (AML) according to world health organization (WHO) 2016 classification\n2. Presence of FLT3-mutation(s) at inclusion: in case of FLT3-ITD, the ITD\u002Fwt ratio must be \\> 0.05 ; in case of FLT3-TKD, the mutation must be at D835 or I836 position with a VAF \\> 5% by NGS.\n3. Subjects must be primary refractory or relapsed (R\u002FR) to 1st line intensive chemotherapy (ICT) for AML. Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis.\n\n3a. Primary refractory is defined as no CR or CRi after at least one course of ICT (including \"7+3\", gemtuzumab ozogamycin (GO)-based and CPX-351, including or not midostaurine) or two courses (maximum 4) of AZA and venetoclax 3b. Relapse after 1st line ICT for AML is defined as the first hematologic relapse with bone marrow blasts \\>5% after one line of treatment for AML that includes at least one course of ICT (one line of treatment for AML can include induction, re-induction, consolidation, allogeneic HSCT and maintenance) 3c. Relapse after 1st line non intensive chemotherapy for AML is defined as the first hematologic relapse with bone marrow blasts \\>5% after or during treatment by AZA venetoclax regardless of number of cycles 4. 1st line intensive treatment may or may not include previous treatment by tyrosine kinase inhibitor (TKI) except gilteritinib.\n\n5\\. Patients who never received oral azacitidine 6. Age ≥ 18 years 7. Adequate baseline organ function defined by the criteria below:\n\n* adequate renal function as demonstrated by a creatinine clearance ≥ 50 ml\u002Fmin; calculated by the Cockcroft gault formula or measured by 24-hours urine collection\n* aspartate aminotransferase (AST) ≤ 2.5 × ULN\n* alanine aminotransferase (ALT) ≤ 2.5× ULN\n* bilirubin ≤ 1.5 × ULN\n* adequate cardiac function with LVEF ≥45% 8. ECOG \\\u003C 3 (appendix 1) 9. Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule 10. Patient is suitable for oral administration of study drug. 11. A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies: 9a. Not a woman of childbearing potential (WOCBP) as defined in post-menopausal (defined as at least 1 year without any menses) prior to Screening, or documented as surgically sterile (at least 1 month prior to Screening) 9b. WOCBP agrees to follow the contraceptive treatment starting at screening and continue throughout the study period, and for at least 180 days after the final study drug administration 12. Patient must be affiliated to the french social security (health insurance) 13. Signed written informed consent for the study 14. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 60 days after the final study drug administration.\n\n  15\\. Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration.\n\n  16\\. A male subject with female partner(s) of childbearing potential must agree to use contraception starting at screening and continue throughout the study period, for at least 120 days after the final study drug administration.\n\n  17\\. Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after the final study drug administration.\n\nExclusion criteria\n\n1\\. Subjects with any of the following current or previous diagnoses:\n\n1a. AML secondary to prior myeloproliferative syndrome (MPN)\n\n1b. Acute promyelocytic leukemia (APL) and core binding factor (CBF) AML\n\n1c. DNA fragility or bone marrow (BM) failure syndromes\n\n1d. Blastic plasmacytoid dendritic cell neoplasm\n\n1e. Acute lymphoblastic leukemia including ambiguous lineage 2. Patients ≥ 3rd line of treatment, HSCT being not considered as a line of treatment 3. Patients previously treated by AZA as single agent for AML are not allowed 4. Subjects that have previously been treated by gilteritinib 5. Subjects that have previously been treated by oral azacitidine 6. Clinically active central nervous system (CNS) leukemia 7. Subjects who have received more than 1 prior allogeneic HSCT 8. Subjects who have relapsed within 100 days after allogeneic HSCT 9. Presence of Grade 2 or above graft-versus-host disease (GVHD), including acute, chronic, or overlap; or escalation of therapy for GVHD within 14 days prior to randomization 10. Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A (Annexe 7) 11. Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the subject (Annexe 7) 12. Severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis or hyperbilirubinemia) 13. Participant has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC).\n\n14\\. Subject exhibiting evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).\n\n15\\. Isolated extramedullary leukemia relapse 16. History of another malignancy within the past 3 years except basal cell carcinoma of the skin or cervix in situ carcinoma 17. Any other serious medical condition, laboratory abnormalities or psychiatric illness that would place the participant at an unacceptable risk or prevent them from giving informed consent 18. Severe medical or mental condition precluding the administration of protocol treatments 19. persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure (guardianship, curatorship, legal protection), persons under psychiatric care 20. Other comorbidity that the physician judges to be incompatible with conventional intensive chemotherapy which must be reviewed and approved by the study medical monitor before study enrolment 21. Subject with Positive HIV test (due to potential drug-drug interactions). HIV testing will be performed at screening, if required per local guidelines or institutional standards. Subject known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status with undetectable PCR viral load on antivirals (non-exclusionary medications) are not excluded 22. Known hypersensitivity to the study medication 23. Subject has congestive heart failure classified as New York Heart Association Class III and IV unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45% 24. Subject with mean Fridericia-corrected QT interval (QTcF) \\> 450 ms at screening based on central reading 25. Subject with a history of Long QT Syndrome at screening",{"count":220,"type":20},33,[23],"Approximately 30% of adult AML subjects are refractory to induction therapy. Furthermore, of those who achieve CR, approximately 75% will relapse. FLT3-mutated AML comprise an especially poor prognosis group.\n\nUntil now, there was no established standard for relapsed subjects with FLT3 mutations and less than 20% will achieve CR with subsequent treatment.\n\nIn phase 3 Study ADMIRAL Trial, gilteritinib has resulted in CRc in over 25% of subjects receiving 120 mg\u002Fday before on study HSCT. With this treatment, the median overall survival is at 9.3 months, furthermore, gilteritinib was well tolerated at the proposed doses. This study has been designed for R\u002FR patients for which gilteritinib as single agent has been showed to be superior to high- and low-intensity chemotherapy (Perl, NEJM 2019, Supp Table S4) and patients included in this study will receive this treatment. Beyond high- or low-intensity chemotherapy, other options available are best supportive car or other clinical trials.\n\nThe aim of this study is to assess the efficacy and safety of the addition of oral-azacitidine to salvage treatment by gilteritinib in subjects ≥18 years of age with relapsed\u002Frefractory FLT3-mutated acute myeloid leukemia",[224,58,26,225,226],"AML, Adult","FLT3-TKD Mutation","FLT3-ITD","2025-03-20",{"date":229,"type":37},"2025-03-24",{"date":231,"type":37},"2024-01-13",{"date":233,"type":20},"2027-10",{"name":235,"class":70},"French Innovative Leukemia Organisation",{"id":237,"slug":238,"hasResults":11,"nctId":239,"briefTitle":240,"officialTitle":241,"acronym":4,"eligibilityCriteria":242,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":243,"targetDuration":4,"studyType":21,"phases":245,"briefSummary":246,"conditions":247,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":248,"lastUpdatePostDateStruct":249,"startDateStruct":251,"completionDateStruct":253,"leadSponsor":255,"locationsCount":71},"100563211","phase-1-study-of-oral-pclx-001-in-rr-acute-myeloid-leukemia-100563211","NCT06613217","Study of Oral PCLX-001 in R\u002FR Acute Myeloid Leukemia","A Phase 1 Study of Oral PCLX-001 in Relapsed\u002FRefractory (R\u002FR) Acute Myeloid Leukemia (AML)","Inclusion Criteria:\n\n\\-\n\nThe following inclusion criteria apply to ALL (dose escalation and dose expansion) patients:\n\n1. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained before any study-specific procedures are performed.\n2. Male or female patients aged ≥ 18 years\n3. A diagnosis of AML as per 2016 WHO classification (Arber et al, 2016)\n4. Patients must have received at least one prior therapy for AML\n5. Patient must not be eligible for other therapies expected to provide clinical benefit\n6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix A).\n7. The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intrathecal (IT) therapy for patients with controlled CNS leukemia at the discretion of the Investigator. Controlled CNS leukemia is defined by the absence of active clinical signs of CNS disease and no evidence of CNS leukemia on the most recent 2 simultaneous cerebrospinal fluid (CSF) evaluations. (2) Use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. These medications will be recorded in the case-report form.\n8. Patients must have adequate liver function as assessed by the following laboratory tests to be conducted within 7 (±3) days before the first dose of study drug:\n\n   1. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) unless increase is due to hemolysis or congenital disorder such as Gilbert's syndrome\n   2. ALT and AST ≤ 2.5 times ULN or ≤ 5 times ULN for patients with malignant liver involvement\n9. Patients must have adequate kidney function, as assessed by both:\n\n   1. the estimated glomerular filtration rate (eGFR) \\>60 mL\u002Fmin within 7 (±3) days before the first dose of study drug (eGFR to be calculated by the Cockcroft-Gault formula)\n   2. creatinine ≤ 1.5 times the ULN\n10. Adequate cardiac function per institutional normal measured by echocardiography or multi-gated acquisition (MUGA) scan (Left ventricular ejection fraction (LVEF) ≥ 50%)\n11. Ability to take oral medication\n12. Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β- human chorionic gonadotropin (HCG)) pregnancy test obtained within 7 (±3) days before the start of administration of study drug.\n\n    a. Note: A woman is of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy.\n13. Women of childbearing potential and fertile men must agree to use adequate contraception when sexually active from signing of the informed consent form for the full study until at least 6 months after the last study drug administration. Patients must agree to utilize 2 reliable and acceptable methods of contraception simultaneously. A man is considered fertile after puberty unless permanently sterile by bilateral orchiectomy. Men being treated with PCLX-001 are advised not to father a child during and up to 6 months after treatment; prior to treatment, advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment with PCLX-001. Female partners of childbearing potential from male study participants have to use adequate contraception \u002F birth control between signing of the informed consent and 6 months after the last administration of the study drug if the male study participant is not sterilized. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control. Highly effective (failure rate of less than 1% per year) contraception methods, when used consistently and correctly, include:\n\n    1. Combined (estrogen and progestin containing: oral, intravaginal transdermal and progestin-only (oral, injectable, implantable) hormonal contraception associated with inhibition of ovulation.\n    2. Intra-uterine device (IUD) or intrauterine hormone-releasing system (IUS).\n    3. Bilateral tubal occlusion or vasectomized partner (provided that partner is the sole sexual partner and has received medical assessment of the surgical success).\n    4. Sexual abstinence (reliability to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient).\n14. Male patients with a female partner of reproductive potential must use a condom and ensure that an additional form of contraception is also used during treatment and until 6 months after last study drug administration. Patients must agree to utilize reliable and acceptable methods of contraception simultaneously.\n\nExclusion Criteria:\n\n\\-\n\nThe following exclusion criteria apply to ALL (dose escalation and dose expansion) patients:\n\n1. Acute promyelocytic leukemia.\n2. Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study\n3. History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class \\> II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry, or uncontrolled cardiac arrhythmias\n4. Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion)\n5. Moderate or severe hepatic impairment, i.e., Child-Pugh class B or C\n6. Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ counts\u002Flevels \\> 250, no history of AIDs-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on same anti-HIV retroviral medications.\n7. Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator's discretion provided that the disease is stable and sufficiently controlled under treatment.\n8. Infections of CTCAE Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade \\> 2\n9. Uncontrolled seizure disorder requiring therapy with strong CYP3A4 inducers such as carbamazepine and phenytoin\n10. Previous or concurrent cancer that is distinct in primary site or histology from AML, with the exception of the following previous or concurrent cancer types:\n\n    1. Curative treatment for localized cancer completed without signs of recurrence and treatment-related toxicity and low risk of recurrence as assessed by the investigator,\n    2. In-situ prostate cancer, Gleason Score \\\u003C7, prostate-specific antigen \\\u003C10 ng\u002FmL (very low risk and low risk, according to therapy guidelines, e.g., the National Comprehensive Cancer Network guideline; active surveillance \u002F observation is a recommended option).\n11. Inability to swallow oral medications\n12. Any malabsorption condition that may significantly alter the absorption of PCLX-001.\n13. Breastfeeding. Female patients must not breastfeed during treatment and until 4 months after last study drug administration.\n14. Acute toxic effects (CTCAE Grade ≥2) of previous anticancer chemotherapy or immunotherapy that have not yet stabilized or if significant post-treatment toxicities have been observed. (Note however that toxic effects of previous anticancer therapy considered as chronic, such as chemotherapy-induced neuropathy, fatigue, alopecia, or anorexia of CTCAE Grade \\\u003C2, for which further resolution is not expected, do not prevent participation in this study.)\n15. Patients on active radiation therapy or active antineoplastic therapy for a concurrent malignancy at the time of screen. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed.\n16. Previous assignment to treatment during this study\n17. Concomitant participation in another clinical study with investigational medicinal product(s)\n18. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results\n19. Clinically relevant findings in the ECG such as a second- or third-degree atrioventricular block, prolongation of the QRS complex \\> 120 ms (except for bundle branch block pattern), or prolongation of the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise between the investigator and the sponsor's medically responsible person.",{"count":244,"type":20},35,[55],"This is a dose-finding study of oral zelenirstat (PCLX-001) in patients with R\u002FR AML. There are two parts to the study: Dose Escalation and Dose Expansion.",[26],"2025-03-05",{"date":250,"type":37},"2025-03-10",{"date":252,"type":37},"2025-03-03",{"date":254,"type":20},"2026-09-01",{"name":256,"class":180},"Pacylex Pharmaceuticals"]