[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100650619":3},{"organization":4,"armGroups":7,"interventions":42,"overallOfficials":48,"centralContacts":49,"locations":48,"responsibleParty":55,"collaborators":48,"id":57,"slug":58,"hasResults":59,"nctId":60,"briefTitle":61,"officialTitle":62,"acronym":48,"eligibilityCriteria":63,"healthyVolunteers":59,"sex":64,"minAge":65,"maxAge":48,"enrollmentInfo":66,"targetDuration":48,"studyType":69,"phases":70,"briefSummary":73,"conditions":74,"keywords":80,"overallStatus":83,"whyStopped":48,"lastUpdateSubmitDate":84,"lastUpdatePostDateStruct":85,"startDateStruct":88,"completionDateStruct":90,"leadSponsor":92,"locationsCount":48},{"fullName":5,"class":6},"Vitruviae","INDUSTRY",[8,14,18,22,26,30,34,38],{"label":9,"type":10,"description":11,"interventionNames":12},"Arm A","EXPERIMENTAL","ARM A: Adult R\u002FR AML and HR-MDS; VTRU200 infusion",[13],"Biological: VTRU200",{"label":15,"type":10,"description":16,"interventionNames":17},"ARM B","Adult DLBCL post-CAR T failure; VTRU200 infusion",[13],{"label":19,"type":10,"description":20,"interventionNames":21},"ARM C","Adolescent R\u002FR AML with no curative option (12-17 years); VTRU200 infusion",[13],{"label":23,"type":10,"description":24,"interventionNames":25},"ARM D","Expansion at RP2D-Adult R\u002FR AML and HR-MDS; VTRU200 infusion",[13],{"label":27,"type":10,"description":28,"interventionNames":29},"ARM E","Expansion at RP2D: Adult DLBCL post-CAR T failure",[13],{"label":31,"type":10,"description":32,"interventionNames":33},"ARM F","Expansion at RP2D: Adolescent R\u002FR AML with no curative option; VTRU200 infusion",[13],{"label":35,"type":10,"description":36,"interventionNames":37},"ARM G","Expansion at RP2D: Adult solid cancers; VTRU200 infusion",[13],{"label":39,"type":10,"description":40,"interventionNames":41},"ARM H","Expansion at RP2D: Pediatric R\u002FR AML (6 months-11 years) ; VTRU200 infusion",[13],[43],{"type":44,"name":45,"description":46,"armGroupLabels":47,"otherNames":48},"BIOLOGICAL","VTRU200","VTRU200 is an investigational humanized trispecific T-cell engager administered by intravenous infusion. It binds CD3 on T cells and tumor associated glycans and lipids to redirect T-cell cytotoxicity toward malignant cells. Multiple dose levels will be evaluated during dose escalation to determine safety and the recommended Phase 2 dose.",[15,19,23,27,31,35,39,9],null,[50],{"name":51,"role":52,"phone":53,"phoneExt":48,"email":54},"Sonia Sequeira, PhD","CONTACT","18003333333","sonias@vitruviae.com",{"type":56,"investigatorFullName":48,"investigatorTitle":48,"investigatorAffiliation":48,"oldNameTitle":48,"oldOrganization":48},"SPONSOR","100650619","phase-1-grace-a-phase-12a-study-of-vtru200-in-relapsedrefractory-aml-high-risk-mds-dlbcl-post-cart-failure-and-advanced-solid-tumors-100650619",false,"NCT07749976","GRACE: A Phase 1\u002F2a Study of VTRU200 in Relapsed\u002FRefractory AML, High-risk MDS, DLBCL Post CART Failure and Advanced Solid Tumors","A Phase I\u002FIIa Dose Escalation and Expansion Study of VTRU200 in Adult and Pediatric Participants With Relapsed\u002FRefractory AML, HR-MDS, DLBCL Post-CART Failure and Advanced Solid Tumors","Inclusion Criteria:\n\n* 1\\. Adults (≥18 years) with\n\nI. Pathologically confirmed acute myeloid leukemia (AML) according to WHO 2022 criteria. Relapsed or refractory AML, defined as either:\n\n1. Refractory AML: Failure to achieve CR, CRh, or CRi after at least 2 courses of intensive induction therapy.\n2. Relapsed AML: Recurrence after prior CR, CRh, or CRi, documented by one or more of the following: Bone marrow blasts \\>5% by morphologic assessment; persistent reappearance of blasts in peripheral blood by morphologic assessment II. HR-MDS: Pathologically confirmed myelodysplastic syndrome (MDS) according to WHO 2022 criteria, with high-risk disease defined as IPSS-R high-risk or very high-risk (score \\>4.5). Ineligible for allogeneic hematopoietic stem cell transplantation.\n\nIII. DLBCL post-CAR T: histologically confirmed DLBCL per WHO 2022 criteria and relapsed or refractory disease after prior CART therapy. Qualifying post-CAR T treatment failure must be documented at least 1 month after CAR T infusion and include no metabolic response, first metabolic progressive disease, or first relapse after prior response. Prior CART infusion must have occurred at least 1 month before screening. Participants must not be in partial metabolic response or complete metabolic response at screening and must have measurable disease on PET\u002FCT (preferred) or CT\u002FMRI, defined as at least 1 nodal lesion \\>1.5 cm or at least 1 extranodal lesion \\>1.0 cm; if PET is used, lesions must be FDG-avid and consistent with active lymphoma IV. Advanced solid tumors 2. Children (6 months-11 years) and adolescents (12-17 years) with R\u002FR-AML.\n\n1. Children and adolescent refractory AML: Bone marrow contains 1% blasts by multiparametic flow cytometry (MFC) at the end of 2 cycles of induction therapy\n2. Children and adolescent relapsed AML: A single bone marrow sample showing 5% leukemic blasts by MFC, fluorescence in situ hybridization (FISH) testing or other molecular method, or a single bone marrow sample with at least two tests showing 1% blasts such as by MFC, karyotypic abnormality with at least one metaphase similar or identical to diagnosis, FISH abnormality identical to one present at diagnosis (above level of sensitivity of specific FISH probe) or polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of leukemogenic lesion (e.g., fusion, mutation) identical to diagnosis and is quantifiably 1% 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Karnofsky Performance Score (KPS) ≥50% 4. Adequate organ function: I. Hepatic: Serum AST\u002FALT ≤2.5×ULN and total bilirubin ≤1.5×ULN (≤3×ULN if Gilbert's syndrome) II. Renal: Serum creatinine ≤1.5×ULN; Calculated CrCl: ≥40 mL\u002Fmin (Cockcroft-Gault \\[adults\\]; Schwartz formula \\[adolescents\\]; apply if serum creatinine is borderline) III. Cardiac: ejection fraction ≥ 50% and no evidence of pericardial effusion as determined by ECHO IV. Hematologic: WBC count must be ≤20 × 10⁹\u002FL prior to the first dose of study treatment and before each dose in Cycle 1; patients with WBC \\>20 × 10⁹\u002FL may receive cytoreduction with hydroxyurea (up to 4 g\u002Fday) and\u002For leukapheresis per protocol to achieve this threshold, with hydroxyurea held ≥12-24 hours before each study treatment dose 5. Females of childbearing potential must have a negative serum or urine pregnancy test 6. Adults: written informed consent. Adolescents: written patient assent plus parental\u002Fguardian informed consent.\n\n   7\\. Prior treatment with an investigational agent is permitted provided that at least 5 half-lives have elapsed and all treatment-related toxicities have resolved to Grade ≤1 (except alopecia). Prior T-cell engaging, checkpoint inhibitor, or cellular therapies require a minimum washout of 8 weeks.\n\n   Exclusion Criteria:\n   * 1\\. Active central nervous system (CNS) disease requiring treatment. 2. Uncontrolled or clinically significant baseline neurologic disorder (e.g., uncontrolled seizures or severe cognitive impairment\u002Fdelirium), significant psychiatric illness or active substance abuse.\n\n     3\\. Uncontrolled infections including persistent bacteremia\u002Ffungemia despite appropriate therapy, progressive invasive fungal infection, or uncontrolled viral infection with end-organ disease. Active tuberculosis.\n\n     4\\. Concurrent malignancy requiring active systemic therapy. 5. Cytotoxic chemotherapy within 14 days prior to first dose. Targeted anti-leukemic therapy within 7-14 days prior to first dose. Radiotherapy within 14 days prior to first dose (except limited-field palliative radiotherapy). Prior CD3-engaging therapy.\n\n     6\\. T-cell depleting therapy (ATG, alemtuzumab, or equivalent) within 6 months prior to enrollment 7. Severe uncontrolled cardiovascular disease (e.g., NYHA class III\u002FIV heart failure, unstable angina or MI within 6 months, uncontrolled arrhythmia). Severe uncontrolled pulmonary disease (e.g., requiring high-flow oxygen or ventilatory support).\n\n     8\\. Systemic corticosteroids \\>10 mg\u002Fday prednisone equivalent within 7 days prior to first dose.\n\n     9\\. Active autoimmune disease requiring systemic immunosuppression within the past 12 months.\n\n     10\\. Prior allogeneic transplant within 3 months or active graft-versus-host disease (GVHD).\n\n     11\\. Primary immunodeficiency (congenital immunodeficiency disorder requiring ongoing medical management).\n\n     12\\. Known HIV infection. Hepatitis B: HBsAg positive (chronic HBV infection). Hepatitis C: anti-HCV positive (HCV exposure).\n\n     13\\. Pregnant or breastfeeding 14. Known congenital or acquired bleeding disorder, including hemophilia A\u002FB or von Willebrand disease, or other clinically significant coagulopathy 15. History of severe allergic reaction to immunotherapy","ALL","6 Months",{"count":67,"type":68},108,"ESTIMATED","INTERVENTIONAL",[71,72],"PHASE1","PHASE2","About this study\n\nThis is the first study of VTRU200 in people. The main purpose of this study is to find a safe dose of VTRU200 and learn how the medicine behaves in the body. Researchers will also look for early signs that it may help treat cancer.\n\nVTRU200 is an experimental immunotherapy. It is designed to help the body's immune system find and destroy cancer cells while limiting effects on healthy cells.\n\nUnlike many cancer treatments that target a single protein, VTRU200 recognizes stress signals that are commonly found on cancer cells. These signals include certain sugars (called glycans) and fats (called phospholipids) that are present on many types of cancer cells but are uncommon on normal healthy cells. VTRU200 also attaches to immune cells called T cells and helps direct them to attack cancer cells.\n\nBecause VTRU200 targets features that are shared by many cancers, it may continue to work even if cancer cells lose or change individual proteins that other treatments depend on.\n\nWho can take part?\n\nThis study is for people with certain blood cancers that have come back after treatment or have not responded to available treatments. These include:\n\nAcute myeloid leukemia (AML) Higher-risk myelodysplastic syndromes (HR-MDS) Diffuse large B-cell lymphoma (DLBCL) that has returned after CAR T-cell therapy\n\nLater parts of the study may also include adolescents and children with AML.\n\nWhat will happen during the study?\n\nParticipants will receive VTRU200 through a vein (intravenous infusion).\n\nThe study will begin by giving small doses to help determine the safest dose for future participants. If those doses are well tolerated, later participants may receive higher doses.\n\nResearchers will:\n\nMonitor participants closely for side effects. Perform blood tests to measure how VTRU200 moves through and leaves the body. Measure how the immune system responds to treatment. Check whether the cancer shrinks, disappears, or remains under control.\n\nParticipants may receive multiple treatment cycles if they continue to benefit and do not have unacceptable side effects.\n\nWhat are the possible benefits?\n\nVTRU200 may or may not help participants. Information learned from this study may help develop new treatments for people with these cancers in the future.\n\nWhat are the possible risks?\n\nBecause VTRU200 is being tested in humans for the first time, not all side effects are known.\n\nPossible risks include reactions related to activation of the immune system, infusion-related reactions, laboratory test changes, and other side effects. Participants will be monitored closely throughout the study, and medical care will be available if side effects occur.\n\nBrief Study Description\n\nThis first-in-human, open-label, Phase 1\u002F2a study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of VTRU200 in participants with relapsed or refractory acute myeloid leukemia (AML), higher-risk myelodysplastic syndromes (HR-MDS), or diffuse large B-cell lymphoma (DLBCL) following CAR T-cell therapy. VTRU200 is an investigational trispecific T-cell engager that binds stress-associated glycans, phosphatidylserine, and CD3 to redirect T cells toward cancer cells. The Phase 1 dose-escalation portion will determine the recommended Phase 2 dose (RP2D), followed by disease-specific expansion cohorts to further evaluate safety and preliminary antitumor activity.\n\nWhy is this research important?\n\nMany blood cancers eventually stop responding to available treatments. Cancer cells can escape therapy by changing or losing the proteins that many current medicines target.\n\nVTRU200 is designed to recognize stress-related features that many cancer cells share rather than relying on a single protein target. Researchers hope this approach may reduce the chance of treatment resistance while limiting damage to healthy cells. This study will help determine whether VTRU200 can be given safely and whether it shows early signs of helping people with difficult-to-treat blood cancers.",[75,76,77,78,79],"Acute Myeloid Leukemia","Diffuse Large B Cell Lymphoma (DLBCL)","High Risk Myelodysplastic Syndrome","Solid Tumor Malignancies","Pediatric Acute Myeloid Leukemia",[81,82],"T cell engager","TCE","NOT_YET_RECRUITING","2026-08-03",{"date":86,"type":87},"2026-08-06","ACTUAL",{"date":89,"type":68},"2027-01",{"date":91,"type":68},"2029-01",{"name":5,"class":6}]