Rijmenam, Belgium

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.

Iberdomide Vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial for a maintenance therapy, for patients who underwent an induction therapy and autologous stem cell transplantation in the GMMG-HD8/DSMM XIX trial. Investigational Medicinal Product: Iberdomid (oral), isatuximab (subcutaneous administration via a wearable injector system). Randomisation will be performed centrally by GMMG/DSMM offices after verification of the eligibility of the patient. At the time of study inclusion, randomization will be performed into arm A (iberdomide) or arm B (iberdomide + isatuximab). Randomization will be stratified by centrally assessed MRD negativity status (yes vs. no vs. unknown); assessed by NGF from BMA; sensitivity of 10^-5; independent of standard IMWG response) and number of HDM/ASCT (single vs. tandem). Patients randomized in arm A will receive 39 cycles of the drug iberdomide, a Cereblon E3 Ubiquitin Ligase Modulating Drug (CELMoD®) that shares structural similarities to the immunomodulatory compounds (IMiDs) such as thalidomide and lenalidomide. Each cycle will last for 29 days. Patients in arm B will receive the same the 39 cycles of iberdomide plus monoclonal anti-CD38 antibody isatuximab subcutaneously. In both arms, patients will receive 20 mg dexamethasone in cycle 1, on the same days as the isatuximab administration in Arm B. End of study will be after 36 months of the maintenance therapy. There is one primary objective: - Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates (sensitivity 2x10^-6 via next-generation flow cytometry [NGF]) after two years of maintenance therapy. There is one key secondary objective: - PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first. Further secondary objectives are: - Rates of sustained MRD negativity (at sensitivity levels of 10-5 and 2x10^-6 via NGF from BMA) after 1, 2 and 3 years of maintenance therapy. - Conversion from MRD positive to negative (at sensitivity levels of 10^-5 and 2x10^-6 via NGF from BMA). - Rates of best overall response to treatment (BOR). - Rates of partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR). - Time-to-next-treatment (TTNT). - PFS on subsequent line of therapy. - Overall survival (OS). - Improvement of IMWG response categories (PR, VGPR, CR, sCR). - Proportions of patients in both treatment arms maintaining BOR and CR from baseline. - Assessment of quality-of-life (QoL) via the EORTC-QLQC30, EORTC-QLQMY20, and EQ-5D-5L questionnaires.

Randomized Trial in Adult de Novo Ph Positive ALL With Chemotherapy, Imatinib or Ponatinib, Blinatumomab and SCT

Complete Revascularization Versus Culprit Lesion Only PCI in NSTEMI

The complete revascularization versus culprit lesion only PCI in NSTEMI (COMPLETE-NSTEMI) trial aims to investigate whether multivessel complete PCI is superior over culprit-lesion only PCI in patients with NSTEMI and multivessel coronary artery disease.

Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis

A Non-interventional Implementation Study to Evaluate Treatment With Inclisiran (Leqvio®) and Other Lipid Lowering Treatments in a Real-world Setting

German Cardiac Arrest Registry

ITP Registry and Accompanying Biospecimen Collection

Immune thrombocytopenia (ITP) is a rare hematologic disorder that can lead to a greater risk of bleeding or a prolonged bleeding time due to an autoimmune-mediated deficiency of platelets. In recent years, new treatment options for patients with immune thrombocytopenia have emerged. The results of published clinical studies on ITP can only be used for broad patient care to a limited extent, as they are designed for a patient population with clearly defined inclusion and exclusion criteria. Real world data collected from this registry will help to better understand the diagnosis and therapy of ITP patients in everyday treatment and to more effectively direct individual patients to optimal therapy, thus improving their outcomes. By collecting biospecimens, this project will contribute new knowledge to the study of ITP through standardized, systematic, and high-quality collection and storage of patient samples and associated data. The registry collects clinical data from patients diagnosed with ITP at defined points in the course of the disease. The Data collection includes a range of clinical measures, disease-related factors, treatment/treatment course and outcomes, complications during treatment and Qol, fatigue scoring and survival data (up to 5 years). The data are collected prospectively. In addition, patients can be included retrospectively up to 12 months after the initial diagnosis if continuous documentation can be provided at the treatment centre. In both cases, a written declaration of consent is obligatory.

Non-interventional Study to Collect Real-world Clinical and Patient-reported Outcomes in Ovarian Cancer

The "Global Paradise System" Registry