Lebach

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an aromatase inhibitor (AI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the current effective local summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the current effective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + AI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + AI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and Austrian breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + AI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

Objectives and Endpoints Primary Objective: To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A), R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance experimental arm A+I), and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance experimental arm I) as future standard based on the comparison of the investigator-assessed failure-free survival (FFS). Secondary Objectives: * To compare the efficacy of the three treatment arms in terms of secondary efficacy endpoints * To determine the safety and tolerability of ibrutinib during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints Primary Endpoint: FFS defined as time from start of treatment to stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause. Secondary Efficacy Endpoints: * Overall survival (OS) * Progression-free survival (PFS) from randomization, from end of induction immuno-chemotherapy in patients with CR or PR at end of induction immuno-chemotherapy, and from the staging 6 weeks after end of induction assessment (at month 6) * Overall response and complete remission rates at midterm, at end of induction, 3 months after end of induction immunochemotherapy (at month 6) * PR to CR conversion rate during follow-up after end of induction immuno-chemotherapy Secondary Toxicity Endpoints: * Rates of AEs, SAEs, and SUSARs by CTC grade (Version 4.03) during induction immuno-chemotherapy and during periods of follow-up after response to immune-chemotherapy * Cumulative incidence rates of SPMs Exploratory Objectives: * To compare feasibility of ASCT in arm A+I vs. arm A * To compare minimal residual disease status between the three treatment groups * To determine the impact of ibrutinib during induction immuno-chemotherapy and during maintenance therapy on the minimal residual disease status * To determine the prognostic value of minimal residual disease status * To determine the prognostic value of positron emission tomography with fluorine 18-fluorodeoxyglucose * To determine clinical and biological prognostic and predictive factors * To determine the role of total body irradiation (TBI) in ASCT conditioning Exploratory Endpoints: * Rate of successful stem cell mobilisations (success: separation of at least 2x2x10(6) CD34-positive cells, including a back-up) * Rate of molecular remissions (MRD-negative patients) at midterm, at end of induction immuno-chemotherapy, and at staging time-points during follow-up in patients with remission after end of induction immuno-chemotherapy * Time to molecular remission from start of therapy * Time to molecular relapse for patients in clinical and molecular remission after end of induction immunochemotherapy * RD in FDG-PET negative or positive patients after induction and ASCT Exploratory objectives may be evaluated only in a subset of patients according to local standards and resources.

The German-speaking Myeloma Multicenter Group (GMMG) registry is a national, observational, non-interventional, retro-and prospective clinical myeloma registry of multiple myeloma patients in Germany. The registry includes the study database of the prospective trials led by the GMMG, with basic data, diagnosis, therapy and longtime follow-up. The sample size is unlimited. The Myeloma Registry was activated on December 8, 2022. Currently 35 GMMG centers in Germany are participating. The first longtime follow-up data set included in the registry was the GMMG-HD 6 trial. The GMMG-HD6 trial is a phase 3 trial which investigated the efficacy of the addition of the anti-SLAMF7 monoclonal antibody, elotuzumab, to the standard induction and consolidation therapy consisting of lenalidomide, bortezomib and dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma. Target variables of interest are progression-free survival (PFS) from randomization, overall survival (OS), the follow-up time, the cause of death and the therapy free time after first relapse and its treatment. Further objectives will be defined and analyzed for each evaluation. Participations will be observed while the patient is being treated with standard of care until death, lost to follow-up or consent withdrawn. Follow-ups will be documented every six months until the 1st Progression Disease and then annually. The pseudonymized clinical data is stored in a separate database (eCRF) and is monitored centrally on a regular basis. The eCRF contain automated plausibility checks, so called queries.

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 (ASCT) in the GMMG-HD8/DSMM XIX trial or a similar quadruplet induction/consolidation therapy regimen followed by at least one ASCT. 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.

This is a registry study in adult patients with newly diagnosed or refractory/relapsed myeloid neoplasms Investigator's sites: 80-90 sites in Germany and Austria Estimated duration of observation of an individual patient: 10 years maximum Objectives * To register all patients with AML and related neoplasms, newly diagnosed or relapsed/refractory in all AMLSG participating centers (completeness) * To perform rapid analyses of disease-related genetic markers (incidences, treatment recommendations) * To assess patient and family history, as well as patient characteristics * To evaluate treatment response (CR, CRh, CRi) and outcome data (event-free survival \[EFS\], relapse-free survival \[RFS\], cumulative incidence of relapse \[CIR\], cumulative incidence of death \[CID\], overall survival \[OS\]) * To evaluate the impact of measurable residual disease (MRD) by different methods * To assess biological disease features and correlate with clinical outcome data (prognostic and predictive markers) * To store biosamples from all patients (e.g., bone marrow, blood, plasma, normal tissue; e.g., skin biopsy, finger nails, hairs, sputum, or urine)