Dordrecht

Researchers are evaluating the combination of baxdrostat and dapagliflozin in people with chronic kidney disease CKD and high blood pressure hypertension. This Phase III, double-blind, placebo-controlled study aims to assess whether this combination reduces the risk of serious kidney damage, heart failure events, or cardiovascular death compared to dapagliflozin alone. The study includes participants with CKD and hypertension who meet specific kidney function and blood pressure criteria. Participants who are not already taking SGLT2 inhibitors will first complete a 4-week dapagliflozin run-in period. Then, they will be randomly assigned to receive either baxdrostat plus dapagliflozin or a placebo plus dapagliflozin. Baxdrostat dosing may start low and be increased if needed. Study visits will occur at 2, 4, 8, 16, 34, and 52 weeks after randomization, and then approximately every four months until the study ends, which is based on the number of key kidney or heart-related events. Throughout the study, participants will have regular assessments including blood tests to monitor kidney function and potassium levels, blood pressure measurements, and evaluations of heart and kidney health. If participants stop the blinded study drug early, they will continue dapagliflozin if possible and remain in the study for ongoing visits and monitoring. The main outcome is whether the combination treatment reduces the risk of a 50% sustained decline in kidney function, kidney failure, heart failure events, or cardiovascular death over up to 37 months.

Researchers are evaluating elacestrant compared to standard endocrine therapies in adults with node-positive, Estrogen Receptor-positive ER, HER2-negative early breast cancer who are at high risk of cancer returning. The study focuses on those who have had prior endocrine therapy and aims to measure how well elacestrant may prevent invasive breast cancer recurrence over five years. Participants are randomly assigned to receive either 345 mg of elacestrant daily for five years or continue their prior standard endocrine therapy, which may include an aromatase inhibitor anastrozole, letrozole, or exemestane or tamoxifen. The trial is open-label, meaning both participants and researchers know which treatment is given. During the study, participants will have regular assessments to monitor cancer recurrence, survival, side effects, and quality of life. Evaluations include questionnaires on health status and physical functioning at baseline, six months, and annually for up to five years. Safety is tracked through adverse event reporting up to five years plus 28 days. The total participation duration can last up to five years with ongoing monitoring and data collection.

Researchers are evaluating orforglipron to measure its effects on cardiovascular outcomes in adults aged 50 and older who have atherosclerotic cardiovascular disease ASCVD andor chronic kidney disease CKD. This phase 3 study aims to compare orforglipron with a placebo to better understand its impact on major cardiovascular events over about five years. Participants will be randomly assigned to receive either orforglipron orally along with standard care or a placebo orally along with standard care. The study is double-blinded, meaning neither participants nor researchers will know who receives the active drug or placebo during the trial period. During the study, participants will be followed for around five years, with researchers monitoring the time to the first major cardiovascular event and additional outcomes such as cardiovascular and kidney events, changes in kidney function measured by eGFR, and the onset of type 2 diabetes. The study includes regular assessments to track these outcomes and ensure participant safety throughout the long-term follow-up.

This trial focuses on people with relapsed or refractory multiple myeloma who have previously received specific treatments including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies. It aims to study preventive treatments to reduce the occurrence, severity, and duration of taste changes caused by talquetamab, and to better understand the symptoms related to both talquetamab and ramantamig therapies. The study is a Phase 2 trial designed to improve management of oral side effects during treatment. Participants receive talquetamab or ramantamig drugs administered subcutaneously. Some groups receive talquetamab alone, while others receive talquetamab combined with different preventive treatments prophylaxes A, B, C, or D starting before talquetamab therapy. Prophylaxes A, B, and C are given orally, while prophylaxis D is applied topically. Treatment continues until disease progression, unacceptable side effects, withdrawal, or end of study, with prophylaxis lasting up to 12 months but possibly longer based on clinical benefit and doctor decision. During the study, participants will undergo various assessments including taste tests and questionnaires about oral symptoms, quality of life, and body measurements. Researchers will monitor the occurrence and severity of taste changes and other oral toxicities over time, dose adjustments, treatment responses, and safety events. This comprehensive monitoring may last up to 36 months, helping to better characterize the side effects and treatment outcomes for multiple myeloma patients receiving these therapies.

Researchers are evaluating the safety and effectiveness of BGB-16673 compared to pirtobrutinib in adults with relapsed or refractory chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL who have previously been treated with a covalent Bruton tyrosine kinase inhibitor cBTKi. The study is a phase 3, open-label, randomized trial sponsored by BeOne Medicines, aiming to assess treatment options for these patients. Participants are randomly assigned to receive either BGB-16673 or pirtobrutinib, both taken orally. This parallel assignment design compares these two drugs directly. The treatments continue with monitoring up to approximately three years to observe progression-free survival and other outcomes. The study began in September 2025 and is expected to complete in April 2028. During the trial, participants will undergo regular assessments including imaging scans to measure disease status, quality of life questionnaires, and monitoring for adverse events. Outcomes such as overall survival, response rates, duration of response, and time to next treatment are tracked. Safety and quality of life will be evaluated throughout the study period, which may last up to about three years for each participant.

Researchers are evaluating whether adding zilovertamab vedotin to a standard treatment regimen can help people with previously untreated diffuse large B-cell lymphoma DLBCL live longer without the cancer growing or spreading. This phase 3 randomized study compares the combination of zilovertamab vedotin with rituximab plus cyclophosphamide, doxorubicin, and prednisone R-CHP against the standard regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP. The trial is sponsored by Merck Sharp & Dohme LLC and aims to improve treatment outcomes for people with this type of lymphoma. Participants receive treatment in cycles lasting 21 days, for up to 6 cycles approximately 4 months. One group receives zilovertamab vedotin plus rituximab or a rituximab biosimilar, cyclophosphamide, doxorubicin, and prednisone or prednisolone or methylprednisolone, while the comparison group receives rituximab or biosimilar, cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone or methylprednisolone. Both groups may receive 2 additional cycles of rituximab or biosimilar if they have high-risk DLBCL. All infusions are given intravenously on Day 1 of each cycle, with prednisone or similar drugs taken orally on Days 1-5 of each cycle. Throughout the study, participants are closely monitored for progression-free survival up to about 50 months, as well as other outcomes such as overall survival, response to treatment, adverse events, and quality of life changes. Assessments include clinical evaluations during treatment and follow-up periods, with safety monitoring continuing for up to 9 months. This comprehensive follow-up helps researchers understand the effects and tolerability of the treatments over time.

Researchers are evaluating the effectiveness and safety of combining sonrotoclax with either obinutuzumab or rituximab compared to venetoclax plus rituximab in adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma CLLSLL. This Phase 3 randomized study aims to understand which combination offers better progression-free survival and treatment outcomes in patients who have undergone prior therapies. The study has four treatment groups sonrotoclax combined with obinutuzumab, sonrotoclax combined with rituximab, sonrotoclax plus obinutuzumab with treatment guided by minimal residual disease evaluation, and venetoclax combined with rituximab. Sonrotoclax and venetoclax are given orally, while obinutuzumab and rituximab are administered intravenously. Participants receive these treatments according to their assigned group as part of this clinical research. Participants will be monitored for progression-free survival, overall survival, response rates, and minimal residual disease status over several months up to several years. Safety assessments include tracking treatment-emergent adverse events. Quality of life and symptom burden will be evaluated using questionnaires. The study involves regular visits for treatment administration and assessments, with follow-up extending up to 84 months to observe long-term outcomes.

Researchers are evaluating the effectiveness and safety of two fixed-duration treatment combinations for adults with previously untreated chronic lymphocytic leukemia CLL. The study compares sonrotoclax plus zanubrutinib with venetoclax plus acalabrutinib to determine which regimen may better manage this condition. This Phase 3 trial aims to provide insights into these oral therapies for CLL patients needing initial treatment. Participants will be randomly assigned to receive either sonrotoclax and zanubrutinib or venetoclax and acalabrutinib. Both treatment groups will follow a fixed duration of therapy, after which participants will be observed without active treatment. The study drugs are taken orally, and the treatment period is followed by a monitoring phase to evaluate ongoing health. During the study, participants will undergo evaluations including imaging tests to measure disease status and assessments of bone marrow and organ function. Researchers will track progression-free survival and minimal residual disease levels up to about 70 months. Other outcomes such as overall survival, response rates, adverse events, and quality of life will also be monitored. The total study duration extends until November 2031, offering long-term follow-up for participants.

Researchers are evaluating the combination of elranatamab, daratumumab, and lenalidomide compared with the combination of daratumumab, bortezomib, lenalidomide, and dexamethasone in adults with newly diagnosed multiple myeloma who are not candidates for transplant. This phase 3 study aims to determine whether the new combination offers better clinical benefits by assessing safety, tolerability, minimal residual disease negative complete response rates, and progression-free survival. The study has two parts. Part 1 focuses on characterizing the safety and tolerability of elranatamab combined with daratumumab and lenalidomide or with lenalidomide alone, and determining the best dose. Part 2 compares the effectiveness of elranatamab plus daratumumab and lenalidomide against the standard combination of daratumumab, bortezomib, lenalidomide, and dexamethasone in participants with newly diagnosed multiple myeloma. Participants receive study drugs according to their assigned group, and dosing and combinations vary by part and arm. Participants will undergo regular assessments including monitoring of disease status, progression, and response using criteria such as minimal residual disease and progression-free survival. Safety will be monitored through adverse event reporting and laboratory tests. Quality of life will also be evaluated using questionnaires. The study may last up to several years, with follow-up extending up to 97 months to assess long-term outcomes and survival.

Researchers are studying a treatment approach for older adults with acute myeloid leukemia AML who are not suitable for intensive chemotherapy. The study focuses on combining the drug venetoclax with azacitidine, and investigates whether adding cobicistat, a drug that increases venetoclax exposure, can allow for lower venetoclax doses to reduce treatment costs. This is a Phase II trial led by Stichting Hemato-Oncologie voor Volwassenen Nederland, addressing the challenge of treating older, unfit AML patients with fewer side effects and financial burden. Participants receive azacitidine and venetoclax from the first treatment cycle until relapse. Cobicistat is introduced during the run-in phase starting from cycle 2 and during the extension phase starting from cycle 1, aiming to boost venetoclax levels. The study includes a run-in phase with 20 patients and an extension phase, both following this treatment scheme. The trial is single-arm and non-randomized, designed to evaluate pharmacokinetic equivalence and overall survival among other outcomes. Throughout the study, participants will undergo regular monitoring to assess drug levels, treatment response, safety, and side effects for up to 48 months. Researchers will measure remission rates, survival rates, genetic changes, adverse events, and medication adherence. Data on cost savings and treatment effects will also be collected. Patients will be assessed for kidney and liver function, and their progress will be carefully followed to understand the impact of the cobicistat-boosted venetoclax treatment combined with azacitidine.