Pediatric Acute Myeloid Leukemia

This study entails enrolling participants that have been diagnosed with cancer to Olivia, a commercially available AI-enabled personal health platform developed by Tempus. Olivia will serve as the primary interface for eConsent and enrollment into the registry. The platform will also help create a retrospective and prospective registry by working with over 1,000 healthcare systems to combine electronic health records (EHR) and Patient Reported Outcomes (PROs) in a single spot. There may be sub-studies as an add-on to this parent protocol. The sub-studies will address specific goals of the targeted research activities and will usually include additional information specific to each research study.

About this study This 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. VTRU200 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. Unlike 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. Because 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. Who can take part? This study is for people with certain blood cancers that have come back after treatment or have not responded to available treatments. These include: Acute myeloid leukemia (AML) Higher-risk myelodysplastic syndromes (HR-MDS) Diffuse large B-cell lymphoma (DLBCL) that has returned after CAR T-cell therapy Later parts of the study may also include adolescents and children with AML. What will happen during the study? Participants will receive VTRU200 through a vein (intravenous infusion). The 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. Researchers will: Monitor 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. Participants may receive multiple treatment cycles if they continue to benefit and do not have unacceptable side effects. What are the possible benefits? VTRU200 may or may not help participants. Information learned from this study may help develop new treatments for people with these cancers in the future. What are the possible risks? Because VTRU200 is being tested in humans for the first time, not all side effects are known. Possible 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. Brief Study Description This first-in-human, open-label, Phase 1/2a 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. Why is this research important? Many blood cancers eventually stop responding to available treatments. Cancer cells can escape therapy by changing or losing the proteins that many current medicines target. VTRU200 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.

The aim of this project is to study the different diagnostic, predictive, and prognostic profiles, as well as their interrelationships (clinical, biological, genetic) in children with Acute Myeloid Leukemia (AML). Despite numerous research projects on separate cohorts, the prognosis for pediatric AML has not improved. The project therefore consists of pooling research data and existing clinical and biological data from healthcare in a health data warehouse to increase its power. As these diseases are rare and genetic subgroups even rarer, it is crucial to combine all these data sets into a single database to statistically validate our observations. The ultimate goal of this project is to reduce the relapse rate and improve the survival rate of pediatric AML by identifying rare, uncharacterized patient subgroups at high risk of relapse, for whom clinical characteristics and outcomes will be compared with omics data, Leukemia Stem Cells signatures, and drug responses to establish accurate and in-depth profiles.