Talence

Researchers are evaluating a phase 1/2 open-label study to investigate the safety, pharmacokinetics, pharmacodynamics, and clinical effects of an oral drug called Enzomenib (DSP-5336) in patients with acute leukemia, including relapsed or refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), ambiguous lineage acute leukemia, and in certain sites, high-risk myelodysplastic syndromes (MDS) or relapsed multiple myeloma (MM). The study also examines Enzomenib combined with standard AML treatments such as venetoclax plus azacitidine and the intensive chemotherapy 7+3 regimen in patients newly diagnosed with AML who have specific genetic mutations (MLL rearrangement or NPM1 mutation). Participants receive oral Enzomenib either alone or combined with other drugs: venetoclax and azacitidine for a nonintensive treatment group, gilteritinib for a certain relapsed AML group, or intensive chemotherapy with cytarabine and daunorubicin (7+3) for newly diagnosed AML patients. The study includes dose escalation and expansion phases to determine recommended doses for phase 2. Treatment schedules and doses are adjusted based on response and safety, with some patients enrolled in specialized cohorts according to their genetic markers. Throughout the study, participants undergo regular assessments including clinical exams, laboratory tests, bone marrow samples for genetic analysis, and monitoring for adverse events. Researchers measure safety outcomes such as adverse and serious adverse events, determine optimal dosing for phase 2, and evaluate treatment effectiveness by tracking complete response rates. Safety is monitored up to 30 days after the last dose, with dose recommendations made within four months of treatment start and response assessed around six months. The total participation time varies based on individual treatment and study phase.

Researchers are evaluating the safety and tolerance of elritercept, a recombinant fusion protein, in adults with anemia linked to lower-risk myelodysplastic syndromes (MDS). The study aims to understand how elritercept affects red blood cell production and to monitor participants for any worsening of MDS during treatment. This is a Phase 2, open-label study focused on patients with very low, low, or intermediate risk MDS. Participants receive elritercept through subcutaneous injections at different dose levels to assess safety and effects. The study includes multiple parts, with initial treatment cycles followed by an extension phase for those who complete the first part without dose-limiting toxicities and may benefit from continued treatment. The study also includes several cohorts based on specific MDS characteristics and transfusion needs. During the study, participants undergo regular evaluations including blood tests, bone marrow assessments, and monitoring for adverse events. Researchers will track the number of treatment-emergent and serious adverse events for up to 11.2 years. Participants are closely monitored for how well they tolerate elritercept and its impact on anemia and red blood cell production throughout the study duration.

Researchers are evaluating an experimental drug called REGN5837 combined with odronextamab in adults with relapsed or refractory aggressive B-cell Non-Hodgkin Lymphomas (B-NHLs). The study aims to find a safe dose of REGN5837 in the first phase and then assess how well the combination works in the second phase. Additional questions include understanding side effects, drug levels in the blood, and whether the body develops antibodies against the study drugs that might reduce their effectiveness or cause side effects. The study has two parts: dose escalation and dose expansion. In dose escalation, different doses of REGN5837 are tested with odronextamab to determine safety. In the dose expansion phase, the selected dose of REGN5837 is given with odronextamab to evaluate treatment effects. Both drugs are given according to the study protocol. Participants will be monitored for side effects, including serious and special interest events, over approximately five years. Researchers will measure dose-limiting toxicities during the initial treatment cycles and track any adverse events throughout the study. Assessments include imaging to measure disease, laboratory tests, and collection of tumor tissue samples. Some participants may undergo tumor biopsies if safe. The study also looks at how the drugs behave in the body and the immune response to them.

Researchers are collecting clinical data to evaluate the ongoing safety and performance of commercially approved Biosense Webster Inc. (BWI) medical devices used in standard cardiac arrhythmia mapping and ablation procedures. The study focuses on patients diagnosed with cardiac arrhythmias such as atrial fibrillation, supraventricular tachycardia, or ventricular tachycardia. The goal is to confirm safety and performance of these devices in real-world use and to expand the evidence on their application in treating arrhythmias. Participants will be treated with commercially approved BWI medical devices following routine clinical practice. Sub-studies include participants treated with the Varipulse Catheter and the Dual Energy THERMOCOOL SMARTTOUCH SF Catheter. No specific intervention or experimental procedure will be imposed for the study; the treatments follow standard care procedures. During the study, researchers will monitor safety by tracking adverse events related to the devices or procedures within seven days of treatment. They will also assess treatment effectiveness by evaluating specific outcomes such as isolation of pulmonary veins, non-inducibility of targeted tachycardias, and elimination of ventricular arrhythmias. Follow-up and compliance with standard hospital testing and care are expected as part of the participant involvement.

Researchers are studying the biological features of advanced ALK-rearranged non-small cell lung cancer (NSCLC) in patients treated with new generation tyrosine kinase inhibitors (TKIs) as their first therapy. This study is part of the national EXPLORE ALK cohort, a multi-center observational project in France, focusing on patients with this specific genetic alteration. The goal is to better understand the tumor biology and resistance mechanisms by analyzing samples from diagnosis through disease progression. The study collects tumor tissue samples at diagnosis and, when possible, at disease progression for RNA sequencing to identify ALK fusion partners, variants, and co-mutations. Blood samples are also taken at diagnosis, first tumor evaluation, and at progression to analyze circulating tumor DNA (ctDNA) using next-generation sequencing panels that detect mutations, fusions, and other genetic changes. These biological analyses are centralized at specialized centers such as the Léon Bérard Center and Rouen University Hospital. Patients are treated with approved ALK inhibitors like alectinib, brigatinib, lorlatinib, or entrectinib as part of their standard care. Participants will provide blood samples at multiple time points and, if possible, tumor biopsy samples for detailed genetic analysis. Researchers will monitor the progression-free survival from treatment start for up to 72 months. The study involves regular evaluations to assess tumor status and collect biological material to track genetic changes over time. Consent for sample collection and participation in the study is required, and patient data is managed within the national health system framework.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with a female-to-male predominance of 9:1 and a peak incidence at 50 years of age. It is characterized by chronic inflammation and subsequent destruction of exocrine glands, mainly lacrimal and salivary glands, with ocular and oral dryness. Patients also experience joint pain and extreme fatigue. In 20-40% of patients, the inflammatory process extends beyond the exocrine glands and patients experience systemic extra glandular manifestations, with 5-10% developing B-cell lymphoma. Two populations of pSS patients can be defined. Patients with dryness, fatigue, pain and low systemic activity present no or limited long-term extraglandular damage but they have a profoundly reduced quality of life with marked anxiety, depression, and social isolation (Rischmueller 2016)(Meijer, 2009). Patients with high systemic activity have important long-term damage and bad prognosis. To date, there are no approved disease-modifying treatments. Current clinical outcome assessment (COA) tools in pSS have shown important weaknesses (e.g. high placebo response rate) which may hamper demonstration of therapeutic benefit. A novel COA called STAR has recently been developed by the NECESSITY consortium (funded by the Innovative Medicines Initiative) and should allow the identification of new therapeutic options for both patient populations. the investigator aim to demonstrate, thanks to the new STAR outcome measure, efficacy of a combination therapy targeting both B- and T-cells in pSS patients.

Diabetic Foot Ulcer (DFU) is a serious complication seen in people with diabetes, often leading to non-traumatic lower-limb amputation and linked to cognitive decline and lower quality of life. Despite advances in medical care, patients with DFU face a higher risk of early death, which may be due to factors beyond cardiovascular disease, such as inflammation, infections, and cancers. This research aims to be the first prospective, observational, multi-center cohort study in France to explore the 5-year mortality rate and its causes among patients with DFU, along with identifying important factors that predict outcomes. The study will include adults with diabetes who have a foot ulcer or an open lower-limb amputation wound caused by diabetic complications. Participants will be enrolled over a 3-year period starting in 2020 and followed for up to 5 years or until death. This observational study will use data from multiple centers across France and will also evaluate changes in health-related quality of life and the economic impact of DFU on the French healthcare system by using national claims databases. During the study, participants will be monitored for their health status, including the risk of diabetic foot ulcer recurrence or worsening, and causes of death over five years. Researchers will collect data on quality of life and healthcare costs to better understand the burden of DFU. The primary outcome measured will be the DFU risk score assessed 5 years after inclusion, providing insights into prognosis and factors influencing survival and health outcomes in this population.

Colorectal cancer is a common and deadly cancer in France, often spreading to the liver. About 30 to 60% of patients develop liver metastases, and only a small percentage can have these surgically removed right away. For those with tumors that cannot be surgically removed, treatments typically involve chemotherapy combined with targeted drugs like panitumumab or bevacizumab. This research investigates combining systemic chemotherapy with intra-arterial oxaliplatin to improve tumor response and survival in patients with liver-only metastatic colorectal cancer. The study compares intravenous oxaliplatin and intra-arterial oxaliplatin combined with LV5FU2 chemotherapy, with or without irinotecan and targeted therapies, as a first-line treatment. Oxaliplatin is given every 15 days either through a vein or directly into the liver artery. Other drugs include fluorouracil, folinic acid, panitumumab (for patients with specific genetic mutations), bevacizumab, and irinotecan. This treatment aims to improve response rates and reduce side effects compared to standard methods. Participants will undergo regular treatment cycles every 15 days and will be monitored for tumor progression over 24 months after randomization. Assessments include measuring tumor size and progression-free survival. Patients will also be closely monitored for side effects and treatment tolerance. The study aims to determine which treatment approach offers better control of liver metastases and longer survival for patients with colorectal cancer limited to the liver.