De Haan, Belgium

Ground-Breaking Electroporation-based Intervention for PERSistent Atrial Fibrillation Treatment (BEAT PERS-AF)

Atrial fibrillation (AF), the most common arrhythmia, accounts for 1/3rd of Cardiovascular expenses, with over 10 millions affected in Europe. In addition to significant impact on quality of life, AF exposes patients to stroke, heart failure, dementia and death. AF is the most commonly ablated arrhythmia. The Pulmonary Vein Isolation (PVI) is the cornerstone of AF ablation, preventing recurrences, especially in patients with persistent AF. Catheter ablation of AF uses either radiofrequency (RF) or cryothermal (cryo) energy. Common to these thermal energy sources is their reliance on time-dependent conductive heating/cooling and the fact that these modalities ablate all tissue types indiscriminately. The ablation procedure remains long, requires skills and expertise, and has a limited success rate, mostly because of non-durable lesions after PVI implying frequent redo procedures. And these energies are associated with rare but severe complications due to their thermal nature. The goal of BEAT AF is to disrupt AF ablation by achieving durable PVI with permanent, coalescent and transmural ablation lesions using Pulsed Electric Field (PEF) energy. PEF is non-thermal and creates nanoscale pores in cell membranes. Cardiac cells are highly sensitive to PEF unlike phrenic and oesophageal cells. BEAT AF aims to allow assessing preliminary evidence of efficacy and safety of pulsed field energy in persistent AF ablation. For this purpose, a randomized clinical trial will be conducted to provide large clinical data of PEF of 1-year recurrence for persistent AF. The BEAT AF consortium gathers 9 European renowned clinical centres (France, Czech Republic, Germany, Austria, Belgium) to contribute to decrease the huge burden of AF.

Study of Lacutamab in Peripheral T-cell Lymphoma

Study of Ibrutinib + CD20 Antibody and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

Breast Implant-associated Anaplastic Large Cell Lymphoma (BIA-ALCL) Registry

Validation of the O-bridge Protocol: a Prospective, Multicenter Trial

Surgical reconstruction to restore oral function and aesthetics after major ablative surgery in the oral cavity forms a challenge to maxillofacial surgeons, and greatly impacts patient' quality of life (QOL). The "Oncological-bridge (O-bridge®)" protocol, which offers (immediate/delayed) fixed prosthetic rehabilitation in a minimum of sessions and a strongly reduced two-week treatment time. Objective: The investigators aim to demonstrate the added value of the "O-bridge® protocol" in a larger sample size of at least 20 patients eligible for (immediate/delayed) fixed prosthodontic rehabilitation at time of oral cavity (mandibular) reconstruction study design: a prospective, observational cohort study. The "O-bridge® protocol", in which the standardized concept of implant loading and that of oral cavity (mandibular) reconstruction are combined with an adapted prosthetic manufacturing protocol, will be offered to eligible patients requiring ablative surgery because of a benign or malignant tumour of the oral cavity or stage 3-4 osteonecrosis. All patients will be screened by the local maxillofacial surgeon and the prosthodontist to determine eligibility for the procedure. Imaging will be performed as part of routine surgical preparation. Clinical function, as measured with the 11-item scale by Rogers and intelligibility of speech will be assessed by the speech therapist and/or appointed health care employee prior to surgery, 3 months post-surgery and/or at time of implant placement, and at 6 weeks after placement of the O-bridge®. In addition, EORTC quality of life C30 and HN35 questionnaires will also be completed at those time-points, and at 6 months after placement of the O-bridge®. Speech-, food- and prosthetic fit-related items from the Oral Health Impact Profile (OHIP) questionnaire will be completed at 6 weeks and at 6 months after placement of the O-bridge®. Parameters related to implant and bridge stability and patient satisfaction, measured through a 10-point visual analogue scale, will be assessed at 6, 12, 24, 36, 48 and 60 months at routine follow-up consultation after placement of the O-bridge®. As a primary endpoint, the investigators aim to demonstrate that the O-bridge® protocol significantly improves short-term patient' quality of life. Moreover, the investigators aim to demonstrate the validity and reliability of the O-bridge® protocol, based on its short- and long-term biologic implant stability and mechanical stability of the prosthesis. In addition, they aim to measure the impact of the O-bridge® on speech intelligibility.

PTX3-targeted Antifungal Prophylaxis

Background: Invasive mold infections (IMI, grouping infections due to Aspergillus spp [IA] and non-Aspergillus mold) are a major concern in hematological patients, such as those with acute myeloid leukemia (AML) or myelodysplastic syndrome in transformation (MDSit), collectively named AML/MDSit in this protocol, or those undergoing hematopoietic cell transplantation (HCT), with incidence and mortality rates ranging between 3-15% and 25-45%, respectively. Primary antifungal prophylaxis has become the standard of care in such patients. Historically, fluconazole (inactive against IA) was used as prophylaxis and allowed for significant decrease in invasive candidiasis (IC). More recently, posaconazole (a broad-spectrum azole active against IA and other non-Aspergillus filamentous molds) was approved for primary antifungal prophylaxis in high-risk patient categories. However, universal prophylaxis with posaconazole has been challenged, based on the relatively low incidence of IMI and the large number of patients needed to treat. Moreover, administration of broad-spectrum azoles is costly and associated with a large number of complications. Hence, there is an urgent need to optimize antifungal prophylaxis by identifying those patients with the highest risk for IMI to receive a broad-spectrum azole. Pentraxin-3 (PTX3), a pattern recognition receptor, recognizes and binds to Aspergillus conidia, facilitates opsonization and subsequently leads to complement and phagocyte activation. Two single nucleotide polymorphisms (SNPs) in the gene encoding PTX3 have been identified as strong predictors for IA and/or IMI in human studies. What makes PTX3 SNPs different and important in clinical practice is: (i) the extent and reproducibility of basic science data with regards to PTX3 and IA, (ii) the validation of PTX3 SNPs associations with IA in many different patient populations, and (iii) the high frequency of minor allele in the general population. The investigators hypothesize that PTX3 SNPs could be used to identify patients at high risk for IMI, who will benefit the most from antifungal prophylaxis with broad-spectrum azoles. Overall objective: The overall aim of this project is to assess the effectiveness of the use of posaconazole-based antifungal prophylaxis in AML/MDSit patients in high risk group (single or double single homozygotes PTX-3 SNPs). Exploratory objectives are to assess the effectiveness of PTX3 SNPs testing to stratify the use of posaconazole-based antifungal prophylaxis in AML/MDSit patients according to low or high risk genotypes. Methods: Eligible patients will be tested by competitive allele-specific Polymerase Chain Reaction (PCR) from blood-extracted DNA samples for the presence of PTX3 SNPs rs230561 and rs3816527. Randomisation based on genetic testing will be performed at the latest 24h after the first neutropenia day (D0). Patients will be stratified based on genotyping results in two unbalanced strata: stratum A (high-risk PTX3 SNPs) to be randomized 1:1 posaconazole prophylaxis vs fluconazole and stratum-B (low-risk PTX3 SNPs) to be randomized 1:3 in favour of Fluconazole. Patients will be assessed for a diagnosis of possible, probable or proven Invasive Fungal Infections (IFI) based on consensus definition guidelines by the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) groups during 180 days after prophylaxis initiation. Impact: The results of this study may contribute to the optimization of primary antifungal prophylaxis, by preventing IMI while limiting the use of broad-spectrum azoles, thus decreasing complications and costs. This study is one of the first interventional clinical trials to use genetic factors for risk stratification in the field of hematology and infectious diseases, a concept frequently emphasized, however barely transcribed in practice, as precision medicine. Furthermore, the scope of the proposed study expands beyond the specific patient population. The results of this study could be used in the design and initiation of similar efforts in other high-risk patient categories, including allogeneic HCT and solid organ transplant (SOT) recipients.

Prospective Registry of Prosthodontic Rehabilitation in Oncology Patients Undergoing Jaw Reconstruction

The number of patients requiring major ablative surgery in the oral cavity, including partial/radical mandibular or maxillary resection, due to a head and neck carcinoma, osteoradionecrosis (ORN), or medication-related osteonecrosis of the jaw (MRONJ) has not been accurately reported. Surgical reconstruction to restore oral function and aesthetics forms a challenge to maxillofacial surgeons, and greatly impacts patient' quality of life (QOL). Recently, an active collaboration between the surgeons of the Oral and Maxillofacial Surgery Unit and the prosthodontist (LB) of the Department of Dentistry at the General Hospital Saint-John Bruges led to the development of the "Oncology-bridge (O-bridge)" protocol, which offers (immediate/delayed) fixed prosthetic rehabilitation in a minimum of sessions and a strongly reduced two-week treatment time, consequently accelerating patient' improved QOL at a considerably reduced cost. The investigators aim to develop a prospective database in which patient demographics, surgical, dental, prosthetic and QOL parameters collected during consecutive visits within the framework of routine practice, are being registered for each oncological patient eligible for (immediate/delayed) fixed prosthodontic rehabilitation at time of oral cavity reconstruction This could provide the investigators with more information about potential patient, surgical and prosthetic factors influencing short- and long-term biological and mechanical stability, as well as patient QOL. Moreover, registration of those results could function as a measurement of quality of care, and could be used for sample size calculation for future large prospective trials.

Prospective Registry of 3-dimensional Virtual Treatment Planning of Orthognathic Surgery

3D Volumetric Changes in the Upper Airway After MMA in OSAS Patients and the Implication on QOL: A Prospective Registry

Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

This is a multicenter, open label, Phase 2b study of the selective inhibitor of nuclear export (SINE) selinexor (40 or 60 milligrams [mg]) given orally (PO) to participants with R/R DLBCL). The study is being conducted in 2 parts (Part 1 and Part 2). For Part 1, a fixed 60 mg dose of selinexor is given orally to 130 participants with R/R DLBCL who have no therapeutic options of demonstrated clinical benefit and who meet eligibility criteria and have none of the exclusion criteria will be enrolled to receive selinexor until either disease progression or intolerance has occurred. For Part 2, approximately 110 participants (55 in each arm) are planned to be enrolled. Participants will be randomized (open label) in a 1:1 ratio to either Arm A (40 mg) or Arm B (60 mg) and will be stratified based on history of prior autologous stem cell transplantation (ASCT) versus no prior ASCT. All the participants will be followed until disease progression and/or death.