[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Princess Maxima Center for Pediatric Oncology\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":367},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,13,0,[8,46,76,106,131,170,200,223,244,272,297,315,337],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":30,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100464453","phase-3-interfant-21-treatment-protocol-for-infants-under-1-year-with-kmt2a-rearranged-all-or-mixed-phenotype-acute-leukemia-100464453",false,"NCT05327894","Interfant-21 Treatment Protocol for Infants Under 1 Year With KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia","Interfant-21 International Collaborative Treatment Protocol for Infants Under One Year With KMT2A-rearranged Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia.","Interfant-21","Inclusion Criteria:\n\n1. Patients with newly diagnosed B- precursor ALL or B-cell MPAL (single lineage) according to the WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017), with KMT2A-rearrangement.\n2. ≤ 365 days of age at the time of diagnosis of ALL.\n3. Written informed consent of the parent(s) or other legally authorized guardian of the patient according to local law and regulations.\n\nExclusion criteria for blinatumomab:\n\n1. KMT2A-wildtype patients.\n2. Multilineage MPAL\n3. T-ALL.\n4. Age \\> 365 days at the time of diagnosis.\n5. Down syndrome.\n6. Relapsed ALL.\n7. Treatment with systemic corticosteroids (equivalent prednisone \\>10 mg\u002Fm2\u002Fday) for more than one week and\u002For any chemotherapeutic agent in the 4-week interval prior to diagnosis. Patients who received corticosteroids by aerosol are eligible for the study.\n\nIf exclusion criteria for blinatumomab are met, the patient should be treated according to the protocol but without blinatumomab.","ALL","1 Day","1 Year",{"count":21,"type":22},160,"ESTIMATED","INTERVENTIONAL",[25],"PHASE3","This study is a treatment protocol with blinatumomab for infants under 1 year old who are diagnosed with acute lymphoblastic leukemia with a specific unfavorable genetic alteration. The purpose of the study is to improve the outcome of this disease in infants.",[28,29],"Acute Lymphoblastic Leukemia","Mixed Phenotype Acute Leukemia",[31,32],"infant under one year","KMT2A-wildtype","RECRUITING","2026-04-08",{"date":36,"type":37},"2026-04-13","ACTUAL",{"date":39,"type":37},"2022-12-15",{"date":41,"type":22},"2030-09",{"name":43,"class":44},"Princess Maxima Center for Pediatric Oncology","OTHER",115,{"id":47,"slug":48,"hasResults":11,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":52,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":54,"enrollmentInfo":55,"targetDuration":4,"studyType":23,"phases":57,"briefSummary":60,"conditions":61,"keywords":63,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":67,"lastUpdatePostDateStruct":68,"startDateStruct":70,"completionDateStruct":72,"leadSponsor":74,"locationsCount":75},"100623683","phase-1-an-imaging-study-of-anti-gd2-800cw-in-patients-with-neuroblastoma-100623683","NCT07399821","An Imaging Study of Anti-GD2-800CW in Patients With Neuroblastoma","A Phase Ib\u002FII First-in-human Imaging Study of Anti-GD2-800CW in Patients With Neuroblastoma","GLOW-FISH","Inclusion Criteria:\n\n* Patients with the diagnosis of neuroblastoma as defined by histopathology (confirmed by the PMC Department of Pathology), who will be operated for NB as standard of care procedure\n* Patients older than 1 year of age and not older than 18 years.\n* Written informed consent from patients and\u002For from parents or legal guardians, according to local law and regulations\n\nExclusion Criteria:\n\n* Previous treatment with Dinutuximab-beta, either alone or in combination with chemotherapy\n* Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within during the screening period and before the administration of the IMP.\n* Breast feeding.\n* Sexually active participants not willing to use highly effective contraceptive method (pearl index \\\u003C1) as defined in CTFG HMA 2020 (Appendix I) during trial participation and until 6 months after end of protocol therapy.\n* Patients that received prior treatment with chimeric antibodies.","18 Years",{"count":56,"type":22},22,[58,59],"PHASE1","PHASE2","This is a non-randomized, open label phase Ib\u002FII dose-escalation and expansion study designed to define the recommended dose of anti-GD2-800CW in pediatric neuroblastoma patients. The aim of this imaging study is to determine a safe and effective dose of anti-GD2-800CW for intra-operative detection of neuroblastoma using NIR fluorescence.",[62],"Neuroblastoma",[62,64,65,66],"Fluorescence Guided Surgery","NIR fluorescence","pediatric oncology","2026-02-02",{"date":69,"type":37},"2026-02-10",{"date":71,"type":37},"2025-11-05",{"date":73,"type":22},"2027-05-01",{"name":43,"class":44},1,{"id":77,"slug":78,"hasResults":11,"nctId":79,"briefTitle":80,"officialTitle":81,"acronym":82,"eligibilityCriteria":83,"healthyVolunteers":11,"sex":17,"minAge":84,"maxAge":85,"enrollmentInfo":86,"targetDuration":4,"studyType":88,"phases":4,"briefSummary":89,"conditions":90,"keywords":93,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":97,"lastUpdatePostDateStruct":98,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":105},"100460013","international-leukemia-target-board-100460013","NCT05270096","International Leukemia Target Board","International Concerted Action to Allocate Children, Adolescents and Young Adults With Relapsed and Refractory Leukemia\u002FLymphoma to the Right Therapy.","iLTB","Inclusion criteria\n\n1. The patient has been diagnosed with a R\u002FR hematological malignancy;\n2. The patient is less than 18 years of age at the time of first diagnosis and less than 25 years at the time of inclusion with relapse\u002Frefractory hematological malignancy;\n3. The patient is treated in a pediatric\u002FAYA setting or study protocol, with no current standard of care treatment;\n4. The patients' life expectancy is at least 6 weeks;\n5. The patient has undergone any sort of molecular profiling of his\u002Fher tumor and the re-sults of this analysis are available;\n6. The patient has undergone flow cytometry in a certified lab and results are available;\n7. Written informed consent of patient and\u002For parent(s)\u002Fguardian(s) to discuss the patient in the iLTB according to local law and legislation has been obtained.\n\nExclusion criteria: none defined","0 Years","25 Years",{"count":87,"type":22},600,"OBSERVATIONAL","The iLTB is a proof-of-concept initiative for children with r\u002Fr hematological malignancies, in which available treatment options will be prioritized by actionable events in a harmonized and uniform setting across Europe by a team of biologists, bio-statisticians, bio-informaticians, disease experts, geneticists, flow-experts, clinical trial physicians and also the treating physician.\n\nThe iLTB will discuss molecular (genetic lesions), immunophenotypic\u002Fsurface antigen markers information and, if available, drug response profiles to prioritize these events taking into account the treatment history and treatment intention (bridging to hematopoietic stem cell transplanation\u002FCAR-T or palliative) of each patient followed by a registry to monitor how often iLTB advice has been followed, which other therapy was chosen (off-label, compassionate use) and what the patient outcome is at an aggregated level.\n\nAs such the iLTB is non-interventional as it mainly provides advice and registers data on patients discussed in the iLTB.",[91,92],"Relapsed Hematologic Malignancy","Refractory Hematologic Malignancy",[94,95,96],"Tumor board","Relapsed leukemia","Treatment prioritization","2026-01-07",{"date":99,"type":37},"2026-01-09",{"date":101,"type":37},"2022-12-31",{"date":103,"type":22},"2032-06-01",{"name":43,"class":44},7,{"id":107,"slug":108,"hasResults":11,"nctId":109,"briefTitle":110,"officialTitle":111,"acronym":112,"eligibilityCriteria":113,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":85,"enrollmentInfo":114,"targetDuration":4,"studyType":23,"phases":116,"briefSummary":117,"conditions":118,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":122,"lastUpdatePostDateStruct":123,"startDateStruct":125,"completionDateStruct":127,"leadSponsor":129,"locationsCount":130},"100433552","phase-1-brigatinib-in-pediatric-and-young-adult-patients-with-alk-alcl-imt-or-other-solid-tumors-100433552","NCT04925609","Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors","A Phase I\u002FII Study of Brigatinib in Pediatric and Young Adult Patients With ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors or Other Solid Tumors","Briga-PED","Inclusion Criteria:\n\n1. Patients must be 1 and \\\u003C 26 years of age at the time of enrollment, and able to swallow brigatinib tablets at the time of enrollment, with a minimum weight of 10 kg. Note: for phase 1 only patients ≤18 years old will be eligible, A liquid formulation for children with a weight lower than 10 kg or for those that cannot swallow tablets is in development.\n2. Patients must have a confirmed diagnosis of cancer histologically at baseline. In patients where a repeat biopsy at relapse (or moment of refractory disease) is considered not feasible by the treating physician, archived material from diagnosis needs to be available for central review.\n3. Patients are required to provide prior results showing an activating ALK aberration in the tumor per local laboratory results, and material needs to be available for central laboratory confirmation of ALK status. For ALK+ ALCL, detection of ALK with immunohistochemistry (IHC) is sufficient for inclusion, all others require molecular evidence of a ALK fusion gene or mutation by FISH, PCR or NGS. ALK detection will be confirmed centrally with FISH.\n4. For Phase 1:\n\n   * Patients with ALCL must be relapsed\u002Frefractory or intolerant to standard therapies. Refractory disease for ALCL is defined as:\n\n     o no response to ALCL99\u002Fother standard of care chemotherapy (SD or PD of measurable lesions), and\u002For\n\n     o MRD-positivity by qualitative PCR for NPM-ALK prophase after one block ALCL99\u002Fother standard of care chemotherapy (before the second course of chemotherapy).\n   * Patients with relapsed\u002Frefractory (R\u002FR) IMT must not be suitable for curative surgical resection without causing mutilation. Newly diagnosed patients with unresectable ALK+ IMT, or when surgery would imply severe mutilation may also be included, as well as metastatic disease.\n   * Patients with other solid tumors (excluding IMT) must have relapsed or refractory disease.\n5. For Phase 2, patients must have measurable and\u002For evaluable disease:\n\n   * Patients with ALCL must be relapsed\u002Frefractory. Refractory disease for ALCL is defined as:\n\n     * no response to ALCL99\u002Fother standard of care chemotherapy (SD or PD of measurable lesions), and\u002For\n     * MRD-positivity by qualitative PCR for NPM-ALK prophase after one block ALCL99\u002Fother standard of care chemotherapy (before the second course of chemotherapy).\n   * Patients with R\u002FR IMT Relapsed\u002Frefractory ALK+ IMT, or newly diagnosed, including advanced and metastatic, ALK+ IMT which cannot be surgically resected without causing mutilation\n6. Performance Status: Karnofsky performance status ≥40% for patients \\>16 years of age or Lansky Play Scale ≥40% for patients ≤16 years of age.\n7. Patients must not be receiving other investigational medications (defined as medicinal products not yet approved for any indications, including alternative\u002Fherbal therapies) within 30 days of first dose of study drug or while on study.\n8. For patients receiving prior therapy:\n\n   * Patients who already received previous treatment with ALK inhibitors except for brigatinib can be included in this study.\n   * Patients must have recovered to Grade \\\u003C2 NCI CTCAE v5.0 or to baseline, from any nonhematologic toxicities (except alopecia and peripheral neuropathy) due to previous therapy.\n   * Patients who relapsed while receiving cytotoxic therapy: at least 14 days must have passed since the completion of the last dose of chemotherapy before the first dose of brigatinib can be given.\n   * Patients who have experienced relapse after a prior HSCT are eligible, provided they have no evidence of acute or chronic graft-versus-host disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 45 days posttransplant at the time of enrollment.\n   * Hematopoietic growth factors: before the first dose of brigatinib, at least 7 days must have passed since completion of therapy with granulocyte colony-stimulating factor or other growth factors, and at least 14 days must have passed since completion of therapy with pegfilgrastim.\n   * Biologics and Targeted Therapies:\n\n     o Immunotherapy: Before the first dose of brigatinib, at least 30 days must have passed after the completion of any type of immunotherapy, (i.e. monoclonal antibodies \\[anti-PD1\u002FPDL1\\], tumor vaccines, chimeric antigen receptor \\[CAR\\] T cells, etc.).\n\n     o Other: before the first dose of brigatinib, at least 7 days must have passed since the last dose of a biologic agent. For agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the sponsor's medical monitor\u002Fdesignee.\n\n     o Immunosuppressive therapy: Before the first dose of brigatinib, at least 14 days must have passed after the completion of immunosuppressive therapy (including regimens following stem cell transplant).\n\n     o For symptomatic patients that urgently need relief (i.e. airway obstruction), therapeutic doses of corticosteroids may be administered for a short course (up to 5 days).\n\n     o Radiotherapy (XRT): No washout period is necessary for radiation given to any extramedullary site other than the CNS and lungs; ≥45 days must have passed if patient received prior total body irradiation or craniospinal or cranial XRT; ≥28 days must have passed if patient received radiotherapy to the lung. For patients receiving XRT to both lungs, or in case of stereotactic radiotherapy, the PIs should be consulted before inclusion.\n9. Patients must meet the organ function and system function requirements as stated below:\n\n   * Patients must have adequate renal and hepatic function as indicated by the following laboratory values:\n\n     o Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 x institutional ULN, the patient must have a radioisotope GFR ≥ 70mL\u002Fmin\u002F1.73m2\n     * Adequate liver function defined as: direct bilirubin ≤1.5 times the upper limit of normal (ULN) for age AND AST and ALT must be ≤5 times the ULN for age (unless related to involvement of the liver or histiocytic\u002Fmacrophage inflammatory process).\n   * No clinical, radiological or laboratory evidence of pancreatitis, including o Serum lipase must be \\\u003C2 × the ULN, and\n\n     o Serum amylase must be \\\u003C2 × the ULN.\n   * Absolute neutrophil count: ≥0.75 × 10 9\u002FL, except in case of macrophage activation syndrome (MAS) or bone marrow involvement.\n   * Platelet count o In phase 1: Platelet count: ≥75 × 10\\^9\u002F L, except in case of MAS or bone marrow involvement o In phase 2: : Platelet count: ≥75 × 10\\^9\u002F L, except in case of MAS or bone marrow involvement. For patients post SCT, platelet count ≥50 × 10\\^9\u002F L is accepted.Hemoglobin ≥8 g\u002FdL or 5.0 mmol\u002FL (red blood cell \\[RBC\\] transfusions to achieve this value are allowed with the condition that the patient has no signs of active bleeding or hemolysis).\n10. Adequate cardiac function defined as shortening fraction ≥27% by echocardiogram OR left ventricular ejection fraction of ≥50% by multigated acquisition scan.\n11. Normal QT interval corrected per Fridericia method (QTcF) on screening electrocardiogram (ECG), defined as QTcF of ≤450 ms.\n12. Have a life expectancy of ≥3 months.\n13. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.\n14. Female patients with infants must agree not to breastfeed their infants while on this study.\n15. Contraception:\n\n    • Male and female patients of child-bearing potential must agree to use, an effective method for male and highly effective method for female, of contraception approved by the investigator during the study, following the CTFG recommendations, for at least 8 months for females and for at least 5 months for males after the last dose of brigatinib.\n\n    • Highly effective methods of contraception include (but not exclusively) the following contraceptive methods:\n\n    o combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation\n    * progestogen-only hormonal contraception associated with inhibition of ovulation\n    * intrauterine device (IUD), intrauterine hormone-releasing system (IUS), sexual abstinence.\n16. Voluntary written informed consent according to law and regulations\n\n    \\-\n\nExclusion Criteria:\n\nPatients meeting any of the following exclusion criteria are not to be enrolled in the study:\n\n1. Patients receiving systemic treatment with strong or moderate CYP3A inhibitors or inducers within 14 days or five half-life times whichever the less prior to the first dose of study drug (refer to Section 5.2 for a list of example medications).\n2. Diagnosis of another concurrent primary malignancy.\n3. Clinically significant cardiovascular disease, including any of the following:\n\n   * Myocardial infarction or unstable angina within 6 months of study entry.\n   * History of or presence of heart block, and\u002For clinically significant ventricular or atrial arrhythmias.\n   * Uncontrolled hypertension defined as persistent elevation of systolic and\u002For diastolic blood pressures to ≥95th percentile based on age, sex, and height percentiles despite appropriate antihypertensive management.\n4. Planned non-protocol chemotherapy, radiation therapy, another investigational agent, or immunotherapy while patient is on study treatment.\n5. Any illness that affects gastrointestinal absorption.\n6. Ongoing or active systemic infection, active seropositive HIV, or known active hepatitis B or C infection.\n7. Any pre-existing condition or illness that, in the opinion of the investigator or sponsor, would compromise patient safety or interfere with the evaluation of the safety or efficacy of brigatinib.\n8. Patients with a history of cerebrovascular ischemia\u002Fhemorrhage with residual deficits are not eligible (patients with a history of cerebrovascular ischemia\u002Fhemorrhage remain eligible provided all neurologic deficits have resolved).\n9. Uncontrolled seizure disorder (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs are eligible).",{"count":115,"type":22},65,[58,59],"This is an open-label, phase I-II dose-escalation and expansion study designed to define the recommended dose of brigatinib as monotherapy in pediatric and young adult patients with ALK+ ALCL, IMT or other solid tumors and to evaluate the pharmacokinetics (PK), (long-term) safety, and efficacy of brigatinib in these children.",[119,120,121],"Anaplastic Large Cell Lymphoma, ALK-Positive","Inflammatory Myofibroblastic Tumor","Other Solid Tumor","2025-11-27",{"date":124,"type":37},"2025-12-05",{"date":126,"type":37},"2022-08-18",{"date":128,"type":22},"2033-12",{"name":43,"class":44},2,{"id":132,"slug":133,"hasResults":11,"nctId":134,"briefTitle":135,"officialTitle":136,"acronym":137,"eligibilityCriteria":138,"healthyVolunteers":11,"sex":17,"minAge":139,"maxAge":140,"enrollmentInfo":141,"targetDuration":4,"studyType":23,"phases":143,"briefSummary":144,"conditions":145,"keywords":150,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":162,"lastUpdatePostDateStruct":163,"startDateStruct":165,"completionDateStruct":167,"leadSponsor":169,"locationsCount":4},"100606427","phase-1-hem-ismart-e-capivasertib--venetoclax--dexamethasone-in-pediatric-patients-with-relapsed-or-refractory-hematological-malignancies-100606427","NCT07175415","HEM-iSMART E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","ITCC-104: HEM-iSMART International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Sub-Protocol E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","HEM-iSMART E","Inclusion Criteria:\n\n1. Children ≥ 2 years and ≤ 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion\n2. Performance status: Karnofsky performance status (for patients \\>16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥ 50% (Appendix I).\n3. Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines.\n4. For all oral medications patients must be able to comfortably swallow tablets (except for those for which the AAF is available; nasogastric or gastrostomy feeding tube administration is allowed only if indicated).\n5. Patients must have had advanced molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 of the master protocol for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with advanced molecular profiling at diagnosis may be allowed to be included after discussion with the sponsor.\n6. In the Phase II portion of the trial, 30% of the eligible patients will have to show alterations in the PI3K\u002FAKT\u002FmTOR pathway as follows: PI3K (including PIK3CA, PIK3CB, PIK3R1), AKT and loss of PTEN.\n7. Patients with spinal cord compression should be deemed clinically stable prior to enrolment into the trial.\n8. Adequate organ function:\n\nRENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1):\n\n* Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL\u002Fmin\u002F1.73 m2.\n* Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome).\n* Alanine aminotransferase (ALT)\u002Fserum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)\u002Fserum glutamic oxaloacetic transaminase\u002FSGOT ≤ 5 x ULN.\n\nCARDIAC FUNCTION:\n\n* Shortening fraction (SF) \\>29% (\\>35% for children \\\u003C 3 years) and\u002For left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography.\n* Absence of mean resting QTcF prolongation obtained from triplicate ECG performed at screening according to age group: (aged \\\u003C12 years of age QTcF \\>440msec) (aged ≥12 years QTcF \\>450msec), using the Fridericia correction \\[QTcF formula\\]) or other clinically significant ventricular or atrial arrhythmia.\n\nExclusion Criteria:\n\n1. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.\n2. Sexually active participants of childbearing potential not willing to use highly effective contraceptive method (pearl index \\\u003C1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 30 days after end of study intervention for females and 16 weeks for males.\n3. Breast feeding.\n4. History of another primary malignancy.\n5. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs.\n6. Patients whose tumor present known mutations conferring resistance to venetoclax (e.g. BCL2 mutations of venetoclax binding-site (Gly101Val mutation, Phe104Leu\u002FCys mutations) and capivasertib (e.g. mutations in TSC1, TSC2 and STK11).\n7. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including corticoids.\n8. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n9. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion.\n10. Subjects unwilling or unable to comply with the study procedures.\n11. Previous treatment with capivasertib and venetoclax in combination (Patients who have previously received venetoclax in alternative combinations can be eligible for this sub-protocol. Patients previously treated with capivasertib are not eligible).\n12. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 7, Appendix III for details. In general, strong and moderate inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort). In addition, participants should avoid herbal supplements and ingestion of large amounts of foods and beverages known to potently modulate CYP3A4 enzyme activity during study treatment.\n13. Drugs known to significantly prolong the QT interval and associated with torsade de points (TdP) within 5 half-lives of the first dose of study treatment. Clinically significant electrolyte abnormalities associated with QTc prolongation and\u002For any factors, that in the judgement of the investigator may significantly increase the risk of QTc prolongation. History of QTc prolongation, congenital long QT syndrome, medical history significant for arrhythmia which is not resolved.\n14. Patients who have consumed grapefruit, grapefruit products, Seville oranges (Including marmalade containing Seville oranges) or starfruit within 72 hours prior to the first dose of study drug.\n15. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety\u002Ftoxicity profile of the study treatment (e.g., alopecia and\u002For peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov).\n16. Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial.\n17. Received immunosuppression post allogenic HSCT within one month of study entry.\n18. Metabolic disorders:\n\n    o HbA1c ≥8.0% (63.9 mmol\u002Fmol)\n19. Wash-out periods of prior medication:\n\n    1. CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry.\n    2. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug.\n    3. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT):\n\n       * Autologous HSCT within 2 months prior to the first study drug dose.\n       * Allogeneic HSCT within 3 months prior to the first study drug dose.\n    4. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy, including CAR-T cell therapy other than monoclonal antibodies (e.g. Inotuzumab)\n    5. MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug.\n    6. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery.","2 Years","21 Years",{"count":142,"type":22},42,[58,59],"HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed\u002Frefractory (R\u002FR) ALL and LBL. Sub-protocol E is a phase I\u002FII trial evaluating the safety and efficacy of capivasertib + venetocolax in combination with dexamethasone in children and AYA with R\u002FR ped ALL\u002FLBL whose tumor present with alterations of the PAM pathway, or lacking any mutations.",[28,146,147,148,149],"Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma\u002FLeukaemia) Recurrent","Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma\u002FLeukaemia) Refractory","Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma\u002FLeukaemia) Recurrent","Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma\u002FLeukaemia) Refractory",[151,152,153,154,155,156,157,158,159,160],"Acute lymphoblastic leukemia","relapse","biomarker driven clinical trial","refractory","capivasertib","venetoclax","children","adolescents","young adults","lymphoblastic lymphoma","NOT_YET_RECRUITING","2025-09-09",{"date":164,"type":37},"2025-09-16",{"date":166,"type":22},"2026-10-01",{"date":168,"type":22},"2032-10-01",{"name":43,"class":44},{"id":171,"slug":172,"hasResults":11,"nctId":173,"briefTitle":174,"officialTitle":175,"acronym":176,"eligibilityCriteria":177,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":140,"enrollmentInfo":178,"targetDuration":4,"studyType":23,"phases":180,"briefSummary":181,"conditions":182,"keywords":183,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":162,"lastUpdatePostDateStruct":193,"startDateStruct":194,"completionDateStruct":196,"leadSponsor":198,"locationsCount":199},"100496961","phase-1-hem-ismart-b-dasatinib--venetoclax--dexamethasone--cyclophosphamide-and-cytarabine-in-pediatric-patients-with-relapsed-or-refractory-hematological-malignancies-100496961","NCT05751044","HEM-iSMART-B: Dasatinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Sub-protocol B Dasatinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","HEM-iSMART B","Inclusion Criteria:\n\n1. Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion\n2. Performance status: Karnofsky performance status (for patients \\>12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 50% (Appendix I).\n3. Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines.\n4. For all oral medications patients must be able to comfortably swallow capsules (except for those for which an oral solution is available or dissolving of tablets is allowed based on investigator brochure (IB); nasogastric or gastrostomy feeding tube administration is allowed only if indicated).\n5. Patients must have had advanced molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with advanced molecular profiling at diagnosis may be allowed to be included after discussion with the sponsor.\n6. Patients whose tumor present the following alterations: NUP214-ABL1 fusion or other ABL1 fusion, activating the kinase domain, or ABL1 amplification, or PDGFRβ-fusion with various fusion partners including but not limited to: AGGF1, DOCK2, SATB1, ETV6 and\u002For Patients showing a very deep ex-vivo dasatinib IC50 below 10 nM (Only data generated in centralized laboratory, where a robust DRP platform has been established with a reference cohort in place, will be considered)\n7. Adequate organ function:\n\n   * RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) :\n\n     * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL\u002Fmin\u002F1.73 m2.\n     * Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome).\n     * Alanine aminotransferase (ALT)\u002Fserum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)\u002Fserum glutamic oxaloacetic transaminase\u002FSGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility.\n   * CARDIAC FUNCTION:\n\n     * Shortening fraction (SF) \\>29% (\\>35% for children \\\u003C 3 years) and\u002For left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA.\n     * Absence of QTcF prolongation (QTc prolongation is defined as \\>450 msec on baseline ECG, using the Friedericia correction), or other clinically significant ventricular or atrial arrhythmia.\n\nExclusion Criteria:\n\n1. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.\n2. Sexually active participants not willing to use highly effective contraceptive method (pearl index \\\u003C1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy.\n3. Breast feeding.\n4. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs.\n5. Patients whose tumor present known mutationts confering resistance to venetoclax (e.g. BCL2 mutations of venetoclax binding-site (Gly101Val mutation, Phe104Leu\u002FCys mutations).\n6. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide when applicable, intrathecal agents) and corticoids.\n7. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n\n   a. Additional specifications for SARS-CoV-2 (COVID-19): i. Patients with a recent positive test for SARS-CoV-2 (COVID-19) and no follow-up negative PCR test are not eligible.\n\n   ii. Patients with recent contact to persons with COVID-19 and persons with signs and symptoms of COVID-19 infection must be tested before enrolling. In case of contact with a COVID-19 positive person, at least 5 days should be observed between last contact and COVID testing. A negative PCR test is required to be eligible.\n\n   iii. A negative COVID-19 test result is defined as at least 1 negative PCR test at least 24 hours after resolution of clinical symptoms. Resolution of clinical symptoms is defined as resolution of fever without use of antipyretics and improvement in respiratory symptoms (e.g., cough, shortness of breath).\n\n   iv. Frequency or timing of COVID-19 testing and interval between testing for the above viral clearance criteria may be adjusted to the applicable country and institutional guidelines.\n8. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion.\n9. Subjects unwilling or unable to comply with the study procedures.\n10. Previous treatment with dasatinib and venetoclax in combination (Patients who have previously received any of these two drugs separately can be eligible for this sub-protocol).\n11. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 7, Appendix III and IV for details. In general, CYP3A4 inhibitors\u002FPgp inhibitors, moderate or strong inducers of CYP3A4 or drugs inducing QTc changes (prolongation of the QT interval or inducing Torsade de Points) are not permitted. Among others and not exclusively that relates to antiviral, antifungal, antibiotic, antimalarial, antipsychotic and antidepressive drugs.\n12. Patients who have consumed grapefruit, grapefruit products, Seville oranges (Including marmalade containing Seville oranges) or starfruit within 72 hours prior to the first dose of study drug.\n13. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety\u002Ftoxicity profile of the study treatment (e.g., alopecia and\u002For peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov).\n14. Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial.\n15. Received immunosuppression post allogenic HSCT within one moth of study entry.\n16. History of bone disorders such as osteogenesis imperfecta, rickets, renal osteodystrophy, osteomyelitis, osteopenia, fibrous dysplasia, osteomalacia etc. prior to the underlying diagnosis.\n17. Evidence of clinically active tuberculosis (clinical diagnosis per local practice).\n18. Wash-out periods of prior medication:\n\n    1. CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry.\n    2. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug. Palliative radiation in past 21 days is allowed.\n    3. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT):\n\n       * Autologous HSCT within 2 months prior to the first study drug dose.\n       * Allogeneic HSCT within 3 months prior to the first study drug dose.\n    4. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy other than monoclonal antibodies (e.g. CAR-T therapy)\n    5. MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug.\n    6. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery.",{"count":179,"type":22},26,[58,59],"HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed\u002Frefractory (R\u002FR) ALL and LBL. Sub-protocol B is a phase I\u002FII trial evaluating the safety and efficacy of dasatinib + venetocolax in combination with dexamethasone + Cyclophosphamide and cytarabine in children and AYA with R\u002FR ped ALL\u002FLBL whose tumor present with alterations in the MAPK\u002FSRC pathway.",[28,146,148,147,149],[151,184,185,186,187,188,189,190,191,192],"Relape","Biomarker driven clinical trial","Dasatinib","Refractory","Chemotherapy","Children","Adolescents","Young adults","Lymphoblastic lymphoma",{"date":164,"type":37},{"date":195,"type":22},"2025-10-01",{"date":197,"type":22},"2032-02-01",{"name":43,"class":44},33,{"id":201,"slug":202,"hasResults":11,"nctId":203,"briefTitle":204,"officialTitle":205,"acronym":206,"eligibilityCriteria":207,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":140,"enrollmentInfo":208,"targetDuration":4,"studyType":23,"phases":209,"briefSummary":210,"conditions":211,"keywords":213,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":162,"lastUpdatePostDateStruct":218,"startDateStruct":219,"completionDateStruct":220,"leadSponsor":222,"locationsCount":199},"100496552","phase-1-hem-ismart-c-ruxolitinib--venetoclax--dexamethasone--cyclophosphamide-and-cytarabine-in-pediatric-patients-with-relapsed-or-refractory-hematological-malignancies-100496552","NCT05745714","HEM-iSMART-C: Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol C Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","HEM-iSMART C","Inclusion Criteria:\n\n1. Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion\n2. Performance status: Karnofsky performance status (for patients \\>12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 50% (Appendix I).\n3. Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines.\n4. Patients must have had advanced molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with molecular profiling at first diagnosis lacking molecular diagnostics at relapse or refractory disease may be allowed to be included after discussion with the sponsor.\n5. Patients whose tumor presents alterations in the IL-7R and\u002For JAK-STAT signaling pathways including but not limited to the following are eligible: CRLF2: Rearrangements and mutations leading to CRLF2 overexpression (P2RY8-CRLF2, IGH-CRLF2, and CRLF2 F232C), CRFL2 overexpression; EPOR: Truncating rearrangements or mutations in exon 8, EPOR fusions; JAK1\u002F2\u002F3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion; IL7R: Recurrent or novel missense or in-frame indel mutations in the transmembrane domain; SH2B3: Copy number deletions, or mutations that result in frameshifts or premature termination; JAK2: In frame fusions retaining the tyrosine kinase domain; USP9X truncating mutation or USP9X-DDX3X fusion; STAT5B and DNM2 mutations; PTPN2 deletion described as involved in IL7R\u002FJAK\u002FSTAT pathway activation; IL7R mutations\n6. Adequate organ function:\n\n   * RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) :\n\n     * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL\u002Fmin\u002F1.73 m2.\n     * Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome).\n     * Alanine aminotransferase (ALT)\u002Fserum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)\u002Fserum glutamic oxaloacetic transaminase\u002FSGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility.\n   * CARDIAC FUNCTION:\n\n     * Shortening fraction (SF) \\>29% (\\>35% for children \\\u003C 3 years) and\u002For left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA.\n     * Absence of QTcF prolongation (QTc prolongation is defined as \\>450 msec on baseline ECG, using the Friedericia correction), or other clinically significant ventricular or atrial arrhythmia.\n\n   Exclusion Criteria:\n7. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.\n8. Sexually active participants not willing to use highly effective contraceptive method (pearl index \\\u003C1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy.\n9. Breast feeding.\n10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs.\n11. Patients whose tumor present known mutationts confering resistance to JAK inhibitors: JAK1 Phe958 and Pro960 mutations and JAK2 Y931C mutations.\n12. Patients whose tumor present known mutationts confering resistance to venetoclax (e.g. BCL2 mutations of venetoclax binding-site (Gly101Val mutation, Phe104Leu\u002FCys mutations).\n13. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide when applicable, intrathecal agents) and corticoids.\n14. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n15. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion.\n16. Subjects unwilling or unable to comply with the study procedures.\n17. Previous treatment with ruxolitinib and venetoclax in combination (Patients who have previously received any of these two drugs separately can be eligible for this sub-protocol).\n18. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 7, Appendix III and IV for details. In general, CYP3A4 inhibitors\u002FPgp inhibitors, moderate or strong inducers of CYP3A4 or drugs inducing QTc changes (prolongation of the QT interval or inducing Torsade de Points) are not permitted. Among others and not exclusively that relates to antiviral, antifungal, antibiotic, antimalarial, antipsychotic and antidepressive drugs.\n19. Patients who have consumed grapefruit, grapefruit products, Seville oranges (Including marmalade containing Seville oranges) or starfruit within 72 hours prior to the first dose of study drug.\n20. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety\u002Ftoxicity profile of the study treatment (e.g., alopecia and\u002For peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov).\n21. Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial.\n22. Received immunosuppression post allogenic HSCT within one moth of study entry.\n23. History of bone disorders such as osteogenesis imperfecta, rickets, renal osteodystrophy, osteomyelitis, osteopenia, fibrous dysplasia, osteomalacia etc. prior to the underlying diagnosis.\n24. History of progressive multifocal leuko-encephalopathy (PML).\n25. History of endocrine or kidney related growth retardation prior to the underlying diagnosis.\n26. Evidence of clinically active tuberculosis (clinical diagnosis per local practice).\n27. Wash-out periods of prior medication:\n\n    1. CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry.\n    2. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug. Palliative radiation in past 21 days is allowed.\n    3. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT):\n\n       * Autologous HSCT within 2 months prior to the first study drug dose.\n       * Allogeneic HSCT within 3 months prior to the first study drug dose.\n    4. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy other than monoclonal antibodies (e.g. CAR-T therapy)\n    5. MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug.\n    6. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery.",{"count":179,"type":22},[58,59],"HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed\u002Frefractory (R\u002FR) ALL and LBL. Sub-protocol C is a phase I\u002FII trial evaluating the safety and efficacy of ruxolitinib and venetoclax in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R\u002FR ped ALL\u002FLBL whose tumor present with alterations in the IL7R\u002FJAK-STAT pathway.",[212,146,148,147,149],"Acute Lymphoblastic Leukemia, in Relapse",[214,192,185,215,216,188,217,189,190,191],"acute lymphoblastic leukemia","Ruxolitinib","Venetoclax","Relapse",{"date":164,"type":37},{"date":195,"type":22},{"date":221,"type":22},"2032-02-02",{"name":43,"class":44},{"id":224,"slug":225,"hasResults":11,"nctId":226,"briefTitle":227,"officialTitle":228,"acronym":229,"eligibilityCriteria":230,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":140,"enrollmentInfo":231,"targetDuration":4,"studyType":23,"phases":232,"briefSummary":233,"conditions":234,"keywords":235,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":162,"lastUpdatePostDateStruct":237,"startDateStruct":238,"completionDateStruct":240,"leadSponsor":242,"locationsCount":243},"100489862","phase-1-hem-ismart-d-trametinib--dexamethasone--chemotherapy-in-children-with-relapsed-or-refractory-hematological-malignancies-100489862","NCT05658640","HEM iSMART-D: Trametinib + Dexamethasone + Chemotherapy in Children With Relapsed or Refractory Hematological Malignancies","International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol D: Trametinib + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","HEM-iSMART D","Inclusion criteria\n\n1. Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion. Patients under 6 years old must weigh at least 7 kg at the time of enrollment. Patients over 6 years old must weigh at least 10 kg at the time of enrollment.\n2. Performance status: Karnofsky performance status (for patients \\>12 years of age) or Lansky Play score (for patients\n\n   * 12 years of age) ≥ 50% (Appendix I).\n3. Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines.\n4. Patients must have had molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 of this protocol for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory.\n\n   Patients with molecular profiling at first diagnosis lacking molecular diagnostics at relapse or refractory disease may be allowed to be included after discussion with the sponsor.\n5. Patients whose tumor present RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del, as detected by molecular profiling.\n6. Adequate organ function:\n\n   * RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) :\n\n     * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL\u002Fmin\u002F1.73 m2.\n     * Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome).\n     * Alanine aminotransferase (ALT)\u002Fserum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)\u002Fserum glutamic oxaloacetic transaminase\u002FSGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility.\n   * CARDIAC FUNCTION:\n\n     * Shortening fraction (SF) \\>29% (\\>35% for children \\\u003C 3 years) and\u002For left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA.\n     * Absence of QTcF prolongation (QTc prolongation is defined as \\>450 msec on baseline ECG, using the Fridericia correction), or other clinically significant ventricular or atrial arrhythmia.\n\n   Exclusion Criteria\n7. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.\n8. Sexually active participants not willing to use highly effective contraceptive method (pearl index \\\u003C1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy.\n9. Breast feeding.\n10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs.\n11. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide, intrathecal agents) and corticoids.\n12. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n13. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion.\n14. Subjects unwilling or unable to comply with the study procedures.\n15. Previous treatment with trametinib.\n16. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study.\n\n    See Section 7 and Appendix III for details. Drugs inducing QTc changes (prolongation of the QT interval or inducing Torsade de Points) are not permitted.\n17. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety\u002Ftoxicity profile of the study treatment (e.g., alopecia and\u002For peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov).\n18. Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial.\n19. Received immunosuppression post allogenic HSCT within one moth of study entry.\n20. History or current evidence of retina vein occlusion (RVO) or central serous retinopathy are excluded.\n21. Wash-out periods of prior medication:\n\n    1. CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry.\n    2. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug. Palliative radiation in past 21 days is allowed.\n    3. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Autologous HSCT within 2 months prior to the first study drug dose; Allogeneic HSCT within 3 months prior to the first study drug dose.\n    4. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy other than monoclonal antibodies (e.g. CAR-T therapy)\n    5. MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug.\n    6. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery.",{"count":179,"type":22},[58,59],"HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed\u002Frefractory (R\u002FR) ALL and LBL. Sub-protocol D is a phase I\u002FII trial evaluating the safety and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R\u002FR ped ALL\u002FLBL whose tumor present with alterations in the RAS-RAF-MAPK pathway.",[212,146,148,147,149],[151,192,185,236,188,217,187,189,190,191],"Trametinib",{"date":164,"type":37},{"date":239,"type":37},"2023-11-14",{"date":241,"type":22},"2029-04-01",{"name":43,"class":44},36,{"id":245,"slug":246,"hasResults":11,"nctId":247,"briefTitle":248,"officialTitle":249,"acronym":250,"eligibilityCriteria":251,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":140,"enrollmentInfo":252,"targetDuration":4,"studyType":23,"phases":254,"briefSummary":255,"conditions":256,"keywords":259,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":264,"lastUpdatePostDateStruct":265,"startDateStruct":267,"completionDateStruct":269,"leadSponsor":271,"locationsCount":5},"100604970","phase-1-vyxeos-with-clofarabine-for-pediatric-aml-100604970","NCT07156435","Vyxeos® With Clofarabine for Pediatric AML","A Phase lb Study of Vyxeos® (Liposomal Daunorubicin and Cytarabine) in Combination With Clofarabine in Children With Relapsed\u002FRefractory AML, ITCC-092","VyClo","We will include pediatric patients ≥1 year and ≤21 years with:\n\n* Any ≥ 2nd relapse of AML\n* Refractory AML (defined as ≥ 20% blasts in the bone marrow after standard (re-) induction therapy)\n* Early 1st relapse (defined as relapse within one year from initial diagnosis) of AML\n* Any relapse of AML after prior allogenic HSCT\n* Any relapse of AML with high risk cytogenetic characteristics (as defined in Appendix V)\n\nIn order to be eligible to participate in this study, a subject must meet all of the following criteria:\n\nInitial work-up:\n\n• Complete initial work-up within 7 days prior to study entry, including bone-marrow aspiration, lumbar puncture (without intrathecal therapy)\n\nGeneral condition:\n\n* Lansky play score ≥ 60 for patients \\\u003C16 years of age; or Karnofsky performance status ≥ 60 for patients ≥ 16 years of age (see Appendix I for Performance scales).\n* Life expectancy \\> 6 weeks\n* The patient must have a calculated GFR ≥ 70mL\u002Fmin\u002F1.73 m2.\n* Liver function: total serum bilirubin ≤ 3 mg\u002Fdl or 50 μmol\u002FL and aspartate transaminase (AST) and alanine transaminase (ALT) ≤200 U\u002FL\n* Adequate cardiac function (defined as shortening fraction ≥28% or ejection fraction ≥50%)\n* No evidence of a currently uncontrolled bacterial, viral or parasitic infection\n* No evidence of a fungal infection, defined as either:\n\n  * Pulmonary infiltrates suggestive of a fungal infection at HR-CT (within 3 weeks prior to enrollment)\n  * Positive Aspergillus serum test (galactomannan), according to local laboratory practice (within 3 weeks prior to enrollment)\n* No evidence of isolated extramedullary relapse, including isolated CNS-relapse\n* No evidence of CNS3 or symptomatic CNS leukemia\n* No Down Syndrome\n* No evidence of relapsed\u002Frefractory acute promyelocytic leukemia (APL)\n* No use of any anticancer therapy within 2 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy (note: hematological toxicities do not need to be considered since the patient has overt leukemia)\n* No history of prior veno-occlusive disease (VOD)\n* No known hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin\n* No known copper metabolism deficiency, such as Wilson's disease.\n\nOther:\n\n* For female patients with childbearing potential, a negative test for pregnancy is to be performed before entry on study.\n* Male and female patients must use a highly effective contraceptive method according to the CTFG 2014-guidelines during the study and for a minimum of 6 months after study treatment.\n\nNL72866.041.20 \u002F Vyxeos liposomal and Clofarabine in R\u002FR pediatric AML - ITCC-092 Protocol version: 2.2, 08-04-2021 38 of 80\n\n* Female patients may not breast feed during the study and for a minimum of 3 months after study treatment.\n* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule is required; those conditions should be discussed with the patient before registration in the trial.\n* Before patient registration\u002Frandomization, written informed consent must be given according to ICH\u002FGCP, and national\u002Flocal regulations.\n\nConcomitant treatments:\n\n* Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in the protocol is not allowed.\n* GCSF will not be used for priming and no routine GCSF support is allowed during the 1st course, except for life-threatening infections.\n\nAdditional criteria:\n\n• At least 6 patients must be enrolled with an M3 or a WBC count \\>10x109\u002FL with blasts.",{"count":253,"type":22},25,[58],"Treatment with intensive chemotherapy in AML results in approximately 70% survival in newly diagnosed patients. Prognosis at relapse is worse and is in the 30-40% range. Relapse treatment generally consists of one course of fludarabine, cytarabine and liposomal daunorubicin (FLAG-DNX), followed by a fludarabine and cytarabine course, and subsequent stem-cell transplantation. Cytarabine has been used in combination with fludarabine and cladribine, with the aim to induce synergism by increasing Ara-CTP (active cytotoxic metabolite from ara-C) accumulation, which can be seen as a surrogate marker for cytarabine induced cell-kill. Synergy with cytarabine can also be achieved with clofarabine, which is a potent inhibitor of ribonucleotide reductase, leading to a depletion of normal deoxynucleotides and subsequently to increased Ara-CTP levels. The phase IB trial ITCC020\u002FI-BFM 2009-02 recently reported that clofarabine, replacing fludarabine in the standardly used fludarabine, cytarabine and liposomal daunorubicin (FLAG-DNX) combination regimen, showed high response rates (Overall Response Rate - ORR 68% and 80% at the recommended phase 2 dose - RP2D) in patients with refractory\u002Frelapsed AML, and was generally tolerable, with infectious complications as the main side-effect due to the immunosuppressive properties of clofarabine.\n\nCurrently DNX is unavailable, which urges the need to develop other treatment blocks. The liposomal formulation of Vyxeos®\u002FCPX-351 may be a suitable replacement for DNX, considering the long-term side effect of cardiotoxicity due to anthracyclines which is of primary importance in younger heavily pre-treated patients. The hypothesis is that due to the liposomal formulation there is less penetrance in the cardiac muscle and hence less cardiac damage. The results in pediatric and young adult patients with relapsed\u002Frefractory AML in a COG study using Vyxeos®\u002FCPX-351 at a RP2D of 135 U\u002Fm2 (AAML1421) showed encouraging ORR, with 70% of patients reaching CR\u002FCRi as best response after single agent-treatment with Vyxeos®\u002FCPX-351. Preclinical data have also demonstrated an increased Ara-CTP accumulation and cytotoxicity in cell lines, and were confirmed by tests in ex-vivo blasts from a cohort of AML patients (n=5), when cells were exposed to Vyxeos®\u002FCPX-351 after 4 hours of incubation with fludarabine.\n\nIn this study Vyxeos®\u002FCPX-351 was evaluated in combination with clofarabine with the aim to establish the RP2D of this combination.",[257,258],"Relapsed Pediatric AML","Refractory Pediatric AML",[260,261,262,263],"pediatric AML","relapsed\u002Frefractory","clofarabine","liposomal daunorubicin and cytarabine","2025-08-27",{"date":266,"type":37},"2025-09-05",{"date":268,"type":37},"2020-11-06",{"date":270,"type":22},"2028-12-31",{"name":43,"class":44},{"id":273,"slug":274,"hasResults":11,"nctId":275,"briefTitle":276,"officialTitle":277,"acronym":278,"eligibilityCriteria":279,"healthyVolunteers":11,"sex":17,"minAge":280,"maxAge":54,"enrollmentInfo":281,"targetDuration":4,"studyType":23,"phases":283,"briefSummary":284,"conditions":285,"keywords":287,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":289,"lastUpdatePostDateStruct":290,"startDateStruct":292,"completionDateStruct":294,"leadSponsor":296,"locationsCount":75},"100536254","phase-2-chip-aml22quizartinib-quizartinib--chemotherapy-in-newly-diagnosed-pediatric-flt3-itd-and-npm1wt-aml-patients-100536254","NCT06262438","CHIP-AML22\u002FQuizartinib: Quizartinib + Chemotherapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients","A Phase II, Single Arm, Open Label, Study on the Safety, Efficacy, Pharmacokinetics & Pharmacodynamics of Quizartinib + Chemotherapy and as Single-agent After High Dose Therapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients","CHIP-AML22\u002FQ","Inclusion criteria:\n\n1. Enrollment on CHIP-AML22\u002FMaster:\n\n   Patients must be enrolled on the CHIP-AML22\u002FMaster prior to enrollment on CHIP-AML\u002FQuizartinib linked-trial, and may have received a diagnostic work-up according to the master protocol. Induction treatment can be started as standard of care.\n2. FLT3-ITD+ and wild-type NPM1:\n\n   Presence of FLT3-ITD+ and NPM1 wild type in bone marrow or peripheral blood provided by the local laboratories, as part of standard of care diagnostics. The results of FLT3-ITD testing must be obtained prior to the first dose of quizartinib (e.g., Induction course 1, Day 10).\n3. Age:\n\n   Patients must be from 1 month to ≤ 18 years old at initial diagnosis\n4. Performance status Karnofsky performance status score of \\>50% for subjects \\>16 years of age, and a Lansky performance status score of \\>50% for subjects ≤16 years of age.\n5. Organ function criteria:\n\n   These criteria must be met based on the results before start of any chemotherapy (e.g., MEC) a. Adequate Renal Function Defined as:\n\n   • Calculated eGFR ≥ 50 mL\u002Fmin\u002F1.73 m2 using the Schwartz formula. b. Adequate Liver Function Defined as:\n   * Total or direct (conjugated) bilirubin \\\u003C 1.5xULN for age (≤ 5xULN if related to leukemic involvement), AND\n   * Aspartate transaminase (AST) and alanine transaminase (ALT) \\\u003C5xULN (\\\u003C10×ULN if related to leukemic involvement)\n6. Life expectancy: \\> 6 weeks\n7. Pregnancy test:\n\n   Serum\u002Furine pregnancy test (for all girls ≥ age of menarche) negative within 2 weeks prior to enrollment on the quizartinib linked-trial.\n8. Taking quizartinib:\n\n   Patients must be able to reliably swallow or administer quizartinib by NG tube.\n9. Informed consent:\n\n   Written informed consent\u002Fassent for the quizartinib linked trial from patients and\u002For from parents or legal guardians for minor patients, according to local law and regulations.\n\n   General exclusion criteria:\n   1. Patients with only extramedullary disease\n   2. Uncontrolled or significant cardiovascular disease, including -Diagnosed or suspected congenital long QT syndrome\n\n      -History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes); any history of arrhythmia will be discussed with sponsor, the national coordinator and C.I.the prior to subject's entry into the study.\n\n      -QT interval corrected \\>450 ms: QTc interval corrected with Fridericia's formula (QTcF) for subjects ≥ 6 years of age at the time of enrollment.\n\n      -Left ventricular systolic dysfunction (LVSD), defined as ejection fraction (EF) below 55% during the screening for the CHIP-AML22\u002FMaster protocol.\n\n      -History of uncontrolled angina pectoris or myocardial infarction within 6 months.\n\n      -History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have nohistory of fainting or clinically relevant arrhythmias while using the pacemaker).\n\n      -Heart rate \\\u003C50 beats\u002Fminute on ECG during the screening for the CHIP-AML22\u002FMaster protocol (In case,adolescents with a normal sinusoidal rhythm and no evidence of other cardiac dysfunction will be discussed with sponsor, the national coordinator and C.I. the prior to subject's entry into the study.)\n\n      -Uncontrolled hypertension (e.g., systolic blood pressure and \u002For diastolic blood pressure that is, on repeated measurement, at or above the 95th percentile for sex, age, and height).\n      * History of complete left bundle branch block.\n      * History of New York Heart Association Class 3 or 4 heart failure.\n   3. Known history of HIV or active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)\n   4. Underlying GI disease that may affect absorption of study drug\n   5. Use of strong or moderate CYP3A inducers will be prohibited throughout the duration of the study. Strong CYP3A4 inhibitors will be allowed with a concomitant dose reduction of quizartinib with the exception during the safety run-in.\n   6. History of hypersensitivity to any of the study medications or their excipients.\n   7. Other serious illnesses or medical conditions, that will likely make it impossible to complete treatment according to protocol (e.g., patients who should not be given any of the study medications based on the SmPC)\n   8. Currently participating in other investigational interventional procedures, if it interferes with any endpoints of the quizartinib trial.\n\n2\\) Additional exclusion criteria during safety run-in:\n\n1. Patients with CNS3 disease\n2. Using strong CYP3A4 inhibitors (If patient can stop using strong CYP3A4 inhibitors, he\u002Fshe will be allowed to enroll. In such case, no washout is required for the strong CYP3A4 inhibitor)","1 Month",{"count":282,"type":22},60,[59],"The CHIP-AML22 Master protocol has the overall aim of increasing the cure rate in newly diagnosed pediatric de novo AML patients, while avoiding unnecessary toxicity. The linked Quizartinib trial (CHIP-AML22\u002FQuizartinib) is a phase II, single arm, open label, study on the safety, efficacy, pharmacokinetics and pharmacodynamics of quizartinib in combination with chemotherapy and as single-agent after high dose therapy in newly diagnosed pediatric AML patients with a FLT3-ITD mutation and NPM1 wild-type.",[286],"Acute Myeloid Leukemia in Children",[288],"FLT3-ITD+ NPM1wt AML","2025-07-31",{"date":291,"type":37},"2025-08-05",{"date":293,"type":37},"2024-02-06",{"date":295,"type":22},"2032-06",{"name":43,"class":44},{"id":298,"slug":299,"hasResults":11,"nctId":300,"briefTitle":301,"officialTitle":302,"acronym":4,"eligibilityCriteria":303,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":54,"enrollmentInfo":304,"targetDuration":4,"studyType":23,"phases":306,"briefSummary":307,"conditions":308,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":289,"lastUpdatePostDateStruct":309,"startDateStruct":310,"completionDateStruct":312,"leadSponsor":314,"locationsCount":75},"100515683","phase-3-chip-aml22master-an-open-label-complex-clinical-trial-in-newly-diagnosed-pediatric-de-novo-aml-patients-100515683","NCT05994690","CHIP-AML22\u002FMaster: An Open Label Complex Clinical Trial in Newly Diagnosed Pediatric de Novo AML Patients","An Open Label Complex Clinical Trial in Newly Diagnosed Pediatric de Novo AML Patients - a Study by the NOPHO-DB-SHIP Consortium, Master Protocol","General inclusion criteria for CHIP-AML22\u002FMaster:\n\nPatients are eligible for the study if they fulfil all four criteria below:\n\n1. Newly diagnosed AML as defined by the diagnostic criteria in section 8.1. Note that different blast thresholds may apply for different genetic abnormalities in case of low blast percentages. The origin of AML must be de novo (not secondary to bone marrow failure or therapy-related).\n2. Age ≥ day and ≤18 years old at initial diagnosis.\n3. Written informed consent\u002Fassent from patients and\u002For from parents or legal guardians for minor patients, according to local law and regulations. Informed consent should ideally be obtained before day 7 of induction course 1, as patients that are eligible for the linked quizartinib trial should be enrolled before the end of induction course 1, and in view of the planned Mylotarg® randomisation. Thus, standard of care diagnostics and induction treatment may be started before informed consent has been obtained.\n4. Able to comply with scheduled follow-up and with management of toxicity.\n\nAdditional inclusion criteria for Ri randomization\n\n1. CD33 positivity of leukemic blasts as measured by flow cytometry at diagnosis (bone marrow aspirate and\u002For peripheral blood).\n2. Informed consent for participation in randomization Ri\n\nAdditional inclusion criteria for Rc randomization\n\n1. Patients included in the CHIP-AML22 protocol and stratified to Standard Risk Group according to the stratification algorithm of the protocol\n2. Informed consent for participation in randomization Rc\n\nGeneral exclusion criteria for CHIP-AML22\u002FMaster\n\nPatients are excluded if any of the criteria below are present:\n\n1. Previous chemotherapy or radiotherapy. This includes patients with therapy-related AML after previous cancer therapy. These patients may be treated according to the master protocol but will not be part of the formal study population, and data of these patients will not be collected.\n2. Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia.\n3. Myeloid Leukemia of Down syndrome (ML-DS). Patients with ML-DS are recommended to be treated according to the international ML-DS protocol. Patients with AML and DS older than 5 years who often lack GATA1 mutation and do not have typical myeloid leukemia of DS may be treated according to the master protocol but will not be part of the formal study population, hence data of these patients will not be collected.\n4. Acute promyelocytic leukemia (APL).\n5. Myelodysplastic syndrome (MDS).\n6. Juvenile Myelomonocytic Leukemia (JMML).\n7. Known intolerance to any of the chemotherapeutic drugs in the protocol.\n8. Evidence of cardiac dysfunction (shortening fraction below 28%).\n9. Pregnant or lactating patients, or sexually active female patients of childbearing potential not willing to use an highly effective method of contraception for the duration of study therapy and up to 7 months after the completion of all study therapy.\n10. Sexually active, fertile male patients, not willing to use an effective method of contraception, for the duration of study therapy, and up to 6 months after the completion of all study therapy.\n11. Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in this protocol or in one of the trials linked to this Master protocol, is not allowed.\n12. Patients who in the opinion of the investigator, may not be able to comply with the study requirements of the study.\n13. Patients with known active hepatitis B, hepatitis C, or HIV infection.\n14. Patients for whom informed consent was not obtained.",{"count":305,"type":22},905,[25],"The CHIP-AML22 Master protocol has the overall aim of increasing the cure rate in newly diagnosed pediatric de novo AML patients, while avoiding unnecessary toxicity.",[286],{"date":291,"type":37},{"date":311,"type":37},"2023-07-14",{"date":313,"type":22},"2035-12",{"name":43,"class":44},{"id":316,"slug":317,"hasResults":11,"nctId":318,"briefTitle":319,"officialTitle":320,"acronym":321,"eligibilityCriteria":322,"healthyVolunteers":11,"sex":17,"minAge":323,"maxAge":54,"enrollmentInfo":324,"targetDuration":4,"studyType":23,"phases":326,"briefSummary":327,"conditions":328,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":329,"lastUpdatePostDateStruct":330,"startDateStruct":332,"completionDateStruct":334,"leadSponsor":336,"locationsCount":75},"100553427","phase-1-study-combining-dinutuximab-beta-with-two-chemotherapy-regimens-in-neuroblastoma-100553427","NCT06485947","Study Combining Dinutuximab Beta With Two Chemotherapy Regimens in Neuroblastoma","Phase Ib Study Combining Dinutuximab Beta With Induction Chemotherapy Regimens in Patients With Newly Diagnosed High-risk Neuroblastoma","DBPilot","Inclusion Criteria:\n\n1. Established diagnosis of neuroblastoma Stage M, according to the SIOPEN modified International Neuroblastoma Risk Group (INRG) and to the INSS criteria (Appendix 1).\n2. Age ≥18 months and \\\u003C18 years.\n3. Body weight \\>12 kg.\n4. Alanine transaminase and aspartate aminotransferase \\\u003C10 × upper limit of normal (ULN), total bilirubin \\\u003C1.5 × ULN based on age specific reference ranges.\n5. Calculated glomerular filtration rate \\> 60 mL\u002Fmin\u002F1.73 m2 or serum creatinine \\\u003C1.5 × ULN corrected for age.\n6. Shortening fraction (SF) ≥27% and\u002For left ventricular ejection fraction (LVEF) \\>50% as determined by echocardiography or MUGA.\n7. Able to comply with scheduled follow-up and study procedures.\n8. Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national law and legislation.\n\nExclusion Criteria:\n\n1. Previous cancer-specific treatment for neuroblastoma.\n2. Current use of a prohibited medication or requires any of these medications during the study:\n\n   1. Treatment with corticosteroids is not allowed within 2 weeks prior to the first block of chemotherapy and until 1 week after the last treatment course with dinutuximab beta, except for life-threatening conditions.\n   2. Vaccinations (including seasonal influenza) are not allowed during administration of dinutuximab beta and until 10 weeks after last treatment course.\n   3. Concomitant use of intravenous (IV) immunoglobulins is not allowed.\n   4. Concomitant use of cardioprotectant dexrazoxane is not allowed.\n3. Pregnancy or positive pregnancy test in females of childbearing potential.\n4. Breast feeding.\n5. Sexually active participants not willing to use highly effective contraceptive method\n6. Major surgery within 21 days prior to the first treatment dose\n7. History or documented evidence of severe acute or chronic infection or infectious illness requiring parenteral therapy unless fully healed\n8. Patients with spinal cord involvement\n9. Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug\n10. Have a known immediate or delayed hypersensitivity reaction to study drugs","18 Months",{"count":325,"type":22},38,[58],"The goal of this clinical trial is to to assess the dose level of dinutuximab Beta (DB) when combined with 2 different induction chemotherapy regimens (named GPOH or rapid COJEC) in newly diagnosed high-risk neuroblastoma patients. The main question is:\n\n• to assess the safety and tolerability and identifying the recommended phase II dose and\u002For the maximum tolerable dose of dinutiximab Beta when combined with 2 standard induction chemotherapy regimens\n\nParticipants will receive:\n\n* GPOH + dinutuximab beta infusion duration = 10 mg\u002Fm2 × 5 days (50 mg\u002Fm2\u002Fcourse) in 21-day treatment intervals.\n* Rapid COJEC + dinutuximab beta infusion duration = 10 mg\u002Fm2 × 3 days (30 mg\u002Fm2\u002Fcourse) in 10-day treatment intervals.",[62],"2025-07-02",{"date":331,"type":37},"2025-07-08",{"date":333,"type":37},"2025-01-28",{"date":335,"type":22},"2031-12-01",{"name":43,"class":44},{"id":338,"slug":339,"hasResults":11,"nctId":340,"briefTitle":341,"officialTitle":342,"acronym":343,"eligibilityCriteria":344,"healthyVolunteers":11,"sex":17,"minAge":19,"maxAge":345,"enrollmentInfo":346,"targetDuration":4,"studyType":23,"phases":348,"briefSummary":349,"conditions":350,"keywords":353,"overallStatus":161,"whyStopped":4,"lastUpdateSubmitDate":359,"lastUpdatePostDateStruct":360,"startDateStruct":362,"completionDateStruct":364,"leadSponsor":366,"locationsCount":130},"100594501","phase-1-the-pacman-hu19-trial-a-study-of-the-safety-and-feasibility-of-locally-produced-cd19-targeted-and-human-car-t-cell-therapy-in-children-and-young-adults-with-relapsed-or-refractory-b-cell-malignancies-100594501","NCT07020260","The PACMAN-Hu19 Trial: a Study of the Safety and Feasibility of Locally Produced, CD19-targeted and Human CAR T-cell Therapy in Children and Young Adults With Relapsed or Refractory B-cell Malignancies","The PACMAN-hu19 Trial: a Phase I\u002FII Study to Investigate the Safety and Feasibility of Point-of-care Human CD19 Targeting CAR T-cells in Pediatric and Young Adult Patients With Relapsed or Refractory B-cell Malignancies","PACMAN","Inclusion Criteria:\n\n1. 1-45 years of age.\n2. Patients with relapsed or refractory CD19+ hematological malignancies including, but not limited to:\n\n   1. B-NHL such as Burkitt lymphoma(BL), de novo or transformed diffuse large B cell lymphoma (DLBCL), lymphoblastic lymphoma (LBL), primary mediastinal B cell lymphoma (PMBCL) or indolent lymphoma types with no access to commercially available CAR T-cell therapy or for whom the current production time for commercially available CAR T-cell therapy is not acceptable based on medical need.\n\n      OR\n   2. B-cell precursor ALL failing commercially available CAR T-cell therapy, or for BCP-ALL indications with no access to commercially available CAR T-cell therapy, or for whom the current production time for commercially available CAR T-cell therapy is not acceptable based on urgent medical need (the latter needs to be confirmed by the sponsor).\n3. Measurable disease:\n\n   1. For B-NHL at least one measurable lesion according to the Lugano classification.\n   2. For BCP-ALL at least 0.1% (=10-3) of blasts should be present in the bone marrow measured by molecular MRD, morphology or flow cytometry at screening.\n4. Patients must have exhausted or are ineligible for all registered therapeutic options with curative potential.\n5. Adequate performance score:\n\n   1. Children \\\u003C16 years: Lansky performance status ≥ 60 .\n   2. Children age ≥16 years and \\\u003C18 years Karnofsky performance status ≥ 60.\n   3. Adults ≥18 years ECOG performance status 0, 1 or 2 (ECOG performance status 3 is allowed only when due to underlying disease).\n6. Patients from childbearing potential must be willing and able to use highly effective methods of birth control from first chemotherapy infusion through 12 months after administering the last study treatment.\n7. Patients must be willing to abstain from breast feeding through 12 months after administering the last study treatment.\n8. Patients must agree to refrain from donating blood or organs following treatment with huCAR19 T-cells.\n9. Written informed consent per local law and regulations.\n\n   Additional inclusion criteria phase I part of the study:\n10. The first three patients in the phase I part of the study must be aged 12-45 years, thereafter patients of any age between 1-45 years can be recruited once surrogate endpoint of BCA is reached in ≥60% patients in previous or current dose level and ≤1 DLT occurred at the previous dose level.\n\nExclusion Criteria:\n\n1. Patients with symptomatic CNS involvement will be excluded. After resolution and control of symptoms, patients can be rescreened.\n2. Active uncontrolled or life-threatening infections.\n3. Infection with HTLV-1, HTLV-2, HIV-1, HIV-2, hepatitis B (HbsAg positive) or hepatitis C (anti-HCV positive). Chronic controlled hepatitis B or C infection with undetectable viral load or controlled HIV infection with viral load \\\u003C50 IU\u002Fml and CD4+ T-cell count \\>200\u002Fml may be considered when antiviral prophylaxis or therapy can be administered.\n4. Absolute neutrophil count \\\u003C0.5x109\u002FL unless caused by underlying disease.\n5. Platelet count \\\u003C25x109\u002FL unless caused by underlying disease.\n6. Bilirubin and\u002For transaminases ≤ 2.5 x ULN, unless caused by underlying disease.\n7. Renal insufficiency, defined as:\n\n   1. For adults (≥18 years) glomerular filtration rate (GFR) \\\u003C 45 ml\u002Fmin\u002F1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation:\n\n      predicted GFR (ml\u002Fmin\u002F1.73 m2) = 186 x (serum creatinine in umol\u002FL \u002F 88.7) - 1.154 x (age in years) - 0.203 x (0.742 if patient is female) x (1.212 if patient is black).\n   2. For children (\\\u003C18 years) a serum creatinine based on gender\u002Fage as follows (in µmol\u002Fl):\n\n   Age Male Female 0 to \\\u003C 2 years 53 70 2 to \\\u003C 6 years 70 70 6 to \\\u003C 10 years 88 88 10 to \\\u003C 13 years 106 106 13 to \\\u003C 16 years 132 123 16 to \\\u003C 19 years 150 123\n8. Inadequate pulmonary function defined as baseline oxygen saturation \\\u003C92%, if not caused by underlying disease.\n9. Inadequate cardiac function:\n\n   1. Unstable angina or unstable cardiac arrhythmias.\n   2. NYHA classification \\>II.\n   3. LVSF \\\u003C28% or LVEF \\\u003C45% confirmed by echocardiogram or MUGA scan.\n10. Concurrent malignancy requiring treatment of having been treated \\\u003C3 months before screening except for curatively treated basal cell carcinoma of the skin.\n11. Pregnant women.\n12. Patients unable to participate in the study according to investigator judgement.\n13. Patients not willing or unable to adhere to protocol guidelines or follow-up.\n14. Treatment with allogeneic stem cell transplantation \\\u003C12 weeks from screening or DLI \\\u003C4 weeks from screening or active GVHD requiring systemic treatment. Cutaneous GVHD requiring only topical steroids is allowed.\n15. Hypersensitivity to the active substance","45 Years",{"count":347,"type":22},18,[58,59],"PACMAN is a phase I\u002FII single arm, open-label, multi-center study evaluating the safety of human CD19 CAR-T (huCAR19) produced locally using the Miltenyi Prodigy in children, adolescents and young adults with relapsed\u002Frefractory CD19+ hematological malignancies for whom no standard of care treatment is available.",[351,352],"Leukemia","Lymphoma",[354,355,356,357,358],"CAR T-cell Therapy","relapsed B-cell malignancies","refactory B-cell malignancies","B-NHL","B-cell ALL","2025-06-05",{"date":361,"type":37},"2025-06-13",{"date":363,"type":22},"2025-09-01",{"date":365,"type":22},"2028-09-01",{"name":43,"class":44},""]