Rive, Ukraine

Adjusted High-dose Chemotherapy with Autologous Stem Cell Transplant Vs. Conventional Immunochemotherapy in Elderly PCNSL Patients

Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. However, there are alternative treatment approaches to consider with the potential to improve medical outcomes for this patient population. The current standard of care in Germany and many international centres for patients 65 and older is treatment with R-MP, comprising rituximab, high-dose methotrexate (HD-MTX) and procarbazine followed by maintenance therapy with procarbazine. An alternative approach comprised of a shorter induction treatment with rituximab, HD-MTX and cytarabine (MARTA) followed by age-adjusted high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) was recently shown to be feasible and effective in elderly PCNSL patients considered eligible for high-dose chemotherapy requiring autologous stem cell transplantation. Nevertheless, data evaluating this short duration treatment approach remains scarce, and randomized trials have not yet been published. The objective of the PRIMA-CNS trial is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with R-MP followed by maintenance with procarbazine in elderly patients with newly diagnosed PCNSL; not only regarding survival and remission after treatment but also regarding standards like quality of life (QOL) and treatment related morbidities. Results of this randomized trial will either change the standard of care to an intense and shorter treatment approach or re-define R-MP as a proven treatment standard. In addition, a geriatric assessement is implemented in this trial with the goal to better define transplant eligibility. If this trial shows the superiority of HCT-ASCT, the investigators will establish an improved treatment standard with increased chances for long-term remission and cure and reduced frequency and length of chemotherapy treatment. Considering the poor prognosis of this patient population, this randomized phase III trial is of great clinical importance to provide patients, the patients' families and care takers with optimal treatment.

A Multicentric Cohort and Biomarker Study for Improved Care of Patients with Extrapulmonary Tuberculosis

Background: According to the World Health Organization (WHO), 10 million people fell ill with tuberculosis (TB) in 2019, and 1.4 million people died from this disease. Among infectious agents, Mycobacterium tuberculosis (Mtb) remains the major cause of mortality and morbidity worldwide. Control of the disease is increasingly complicated due to growing numbers of infections with multi-drug resistant strains. In Germany, we witnessed a sharp increase of new cases (7.3 cases per 100,000) in 2015. From 2016 to 2017 the incidence decreased, while the numbers in 2018 (5,429 reported TB cases; 6.5 cases per 100,000) kept almost unchanged. Migrants from high incidence areas account for the majority of all TB patients (67,1% in 2019). While pulmonary TB (PTB) is the most common manifestation, any other organ can be involved. Extrapulmonary TB (EPTB) constitutes for 27,8% (1,321) of all cases in Germany. While the overall incidence of TB is decreasing in industrialized countries, the proportion of EPTB has been constantly increasing in Germany and other European countries. The reasons for this are not fully understood. An extensive retrospective study performed in China showed a significantly higher proportion of multi-drug resistant TB among patients with EPTB than among patients with PTB. This clearly highlights the need for improved EPTB control measures in order to avoid the development of drug resistance and to achieve the goal of TB eradication on a national and international level (e.g. WHO End-TB-strategy) which is further challenged by the SARS-CoV-2 pandemic. The mEX-TB project focuses on EPTB with the main goal of optimizing clinical management of EPTB patients. A prospective clinical cohort of EPTB will be established, involving multiple researchers and clinical sites (Frankfurt, Heidelberg, Borstel, Hamburg, Bonn, Cologne), which will enable us to conduct detailed clinical and translational studies addressing this disease entity. Description: Study population, research design and research methods Adult patients newly diagnosed with EPTB (N=150) will prospectively be enrolled into the study. PTB patients (N=30) will also be included and serve as a control group to test the technical feasibility. In addition, a healthy control group (N=30) will be added, mainly to address aim 1. Clinical data will be collected using standardized questionnaires over the whole treatment period for each individual. Additionally, body fluids (blood, urine) will be collected and stored in a central biobank (Cologne). However, not all contributing centers will be able to provide high quality peripheral blood mononuclear cells (PBMCs) for storage. In order not to lose patients with incomplete sample collections, the cohort study will have several strata: 1. EPTB patients (N=100) with clinical data (e.g. weight gain, imaging results etc.) and a full collection of bio samples (routine laboratory parameters, peripheral blood mononuclear cells (PBMCs), PAXgene RNA/DNA tubes for gene signatures, absolute and relative CD4/CD8 cell count, Vitamin D (25(OH)D), urine, plasma) 2. EPTB patients (N=50) with clinical data (e.g. weight gain, imaging results, microbiology results etc.) plus/minus a partial collection of bio samples (e.g. routine laboratory results, Vitamin D (25(OH)D), PAXgene, plasma) 3. Healthy controls (N=30) and a full collection of bio samples as described for stratum 1 at one timepoint. Data collection Pseudonymized clinical and laboratory data will be recorded at the following time points: diagnosis/ treatment initiation (day 0 / +/- 7 days); 4 weeks post treatment initiation (+/- 7 days); 3 months post treatment initiation (+/- 7 days); 6 months post treatment initiation (+/- 7 days); 3 months post end of treatment (+/- 7 days). In patients requiring treatment of more than 6 months (i.e. multi-drug resistant TB, disseminated TB etc.) data will be collected regularly until end of treatment. Pseudonymization of patient data and acquisition of biomaterial is performed through a patient ID-generator. A paper case report form (CRF) will be used to collect patient data. The CRF data will be then transferred to an electronic database. Outcome: Laboratory based biomarkers for assessing treatment responses similar to sputum conversion used for PTB are not available in most cases of EPTB. Unspecific inflammation markers such as C-reactive protein (CRP) can be utilized to assess early treatment response. We will systematically and longitudinally assess radiologic parameters (lesion size in CT, ultrasonography or MRI), laboratory findings and clinical signs (e.g. weight gain, less pain, absence of fever etc.). We will then exploit response algorithms specifically evaluated for EPTB patients initiating anti-TB treatment. A combination of three clinical parameters will be used 1) improvement in reported symptoms 2) weight gain (any weight gain or ≥ 5% weight gain) 3) regression of lymph node swelling, pleural or peritoneal effusion or other local findings, during and after treatment. A combination of these parameters predicts favorable or unfavorable outcome early during the treatment process. Aims: Our aim is to assess the treatment response using these parameters, supported by two independent clinicians and experts in the field (blind review). Data will be correlated with blood based biomarker findings described below. The main objectives of this study are the development of EPTB specific biomarkers for improved EPTB diagnostics and assessment of treatment responses by correlating immunological and blood based parameters and signatures with clinical features at baseline and longitudinally. For this purpose, our biomarker study will focus on two major aims: Study aim I: Evaluation of blood biomarkers as diagnostic tools for EPTB Sputum or lung fluid based laboratory diagnostics as performed with PTB is not possible in most cases of EPTB. Blood based biomarkers are required. - We will focus on two approaches: 1) blood derived gene expression signatures associated with tuberculosis; 2) T-cell based assays (e.g. TAM-TB assay). - For this aim, we will first investigate markers that have already been analyzed in PTB patients. We will also be able to investigate EPTB specific markers in an unbiased fashion if necessary. Study aim II: Evaluation of blood biomarkers predicting treatment response or failure and cure in EPTB - Predicting cure or the risk of treatment failure is crucial for the management of EPTB. Various outcome definitions for PTB are based on culture and smear results which is not applicable in EPTB. Our aim is to correlate blood based biomarkers with the treatment response which we will assess with well-defined clinical parameters. - For this aim we will continue with our evaluation of plasma IP-10 as a simple and cost-effective treatment response marker. Additional plasma-based markers have been described in our proposal. More complex markers/signatures (gene expression via RNA-seq and T-cell response based) will be applied using technical approaches similar to the ones exploited in Aim 1. We will primarily focus on signatures that have already been evaluated for PTB. The overarching goal of this unique multicenter cohort of patients with EPTB is the development.

Pharmacokinetic Comparison of Efanesoctocog Alfa vs Other EHL-rFVIII Products in Participants With Severe Haemophilia A

Effect of Partially Hydrolyzed Formula With Synbiotics on Skin Barrier Function

Abbott Medical - VERITAS Study

Bemarituzumab in FGFR2b+ Patients with Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed At Least One Prior Line of Palliative Chemotherapy

A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)

Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML

Expected and Actual Preterm-Birth and Parental Distress: Impact on Children's Mental Health

A follow-up survey is conducted based on a previous study on psychological distress in parents with preterm infants (NCT01974531). Medical records and previous questionnaire data will be used for grouping the children based on threat of preterm birth, actual preterm birth and term birth as well as to assess the risk and protective factors in the peripartum period. Parents have been informed within the first study part that a second study part, including their children, would have been followed. Parents were recontacted and asked for participation via telephone or email. Those who agreed, will be contacted via questionnaires in a first step and then in a second step interviewed regarding their own and their children's mental health. The investigators use the following questionnaires to assess children's mental health: Child Behaviour Checklist 6-18R (CBCL 6-18R), Conners 3rd Edition, Social Communication Questionnaire (SCQ), Revised Children's Anxiety and Depression Scale (RCADS). In addition, the investigators conduct clinical interviews with parents on their children's mental health and assess children's cognitive competencies using the Wechsler Intelligence Scale for Children (WISC-V). The following questionnaires are used to assess parental risk and protective factors: State-Trait Anxiety-Depression Inventory (STADI), Parental Stress Scale (PSS), Parenting Scale Short Form (PS), Big Five Inventory Short Form (BFI).

A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS)