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Researchers are evaluating the safety and tolerability of an investigational drug called elritercept, both alone and in combination with the JAK inhibitor ruxolitinib, in adults with myelofibrosis MF. The study also aims to understand how elritercept affects the signs and symptoms of MF, how the body processes the drug, and its effects on anemia when used with or without ruxolitinib. This is a Phase 2 open-label study focusing on participants with anemia related to MF.

Researchers are evaluating momelotinib in adults with low-risk myelodysplastic syndromes LR-MDS who have anemia requiring red blood cell transfusions. The study aims to find out if momelotinib is safe and effective by testing different doses and observing how the body processes the drug. This is a Phase 2, randomized, open-label trial sponsored by GlaxoSmithKline focusing on patients with specific risk classifications of MDS and transfusion needs. Participants will receive momelotinib at one of two dose levels to determine the optimal dose. The study involves monitoring drug levels in the blood and assessing changes in red blood cell transfusion requirements. The treatment period lasts up to 24 weeks for primary outcomes, with extended safety and response monitoring continuing for up to approximately 133 weeks. Throughout the trial, participants will have regular evaluations including blood tests, assessments of anemia improvement, and monitoring for any side effects or adverse events. The main outcomes measured include the percentage of participants achieving transfusion independence for at least 12 weeks and safety events related to treatment. Participants will be followed for up to about 2.5 years to evaluate long-term effects and drug processing in the body.

Researchers are investigating how the drug roginolisib works when combined with the standard treatment ruxolitinib in adults with myelofibrosis MF who have not responded well to JAK inhibitors. This Phase III study focuses on evaluating the safety and tolerability of this combination therapy in patients who have been on ruxolitinib for at least three months without significant reduction of spleen size, aiming to better understand the benefit and risk profile. Participants will receive roginolisib at a dose of 80 mg along with ruxolitinib up to 25 mg twice daily. The study is conducted in two parts the first part enrolls 13 patients to assess initial safety, and the second part enrolls an additional 13 patients to further evaluate the treatment combination. Treatment cycles last 28 days, and participants are expected to remain on treatment for up to 52 weeks. During the study, participants will undergo regular safety assessments including monitoring for adverse events, ECG recordings, laboratory tests, and blood pressure measurements at specific points in each treatment cycle. Researchers will also evaluate biomarker responses, spleen size reduction, symptom improvement using the Myelofibrosis Symptom Assessment Form, and pharmacokinetics of roginolisib. Follow-up for overall survival continues every 12 weeks for up to 96 weeks after the last patient is enrolled.

Researchers are evaluating elritercept for its ability to reduce the need for red blood cell RBC transfusions and its safety compared to epoetin alfa in adults with very low, low, or intermediate risk myelodysplastic syndromes MDS who require regular blood transfusions. The study aims to understand if elritercept improves tiredness, lowers transfusion burden, enhances quality of life, and elicits an immune response. Participants receive either elritercept or epoetin alfa injections. Elritercept is given as a subcutaneous injection starting at 3.75 mgkg every 4 weeks, with possible dose increases to 5.0 mgkg. Epoetin alfa is administered as a subcutaneous injection starting at 450 IUkg once weekly, with possible dose escalation up to 1050 IUkg. The study follows participants for approximately 5 years to monitor treatment effects and safety. During the trial, participants are regularly assessed for transfusion independence, hemoglobin levels, fatigue, quality of life, and hematological improvements. Researchers monitor blood samples for drug concentration and immune response. Safety is evaluated through medical history, lab tests, and adverse event tracking. The main outcome is the proportion of participants achieving RBC transfusion independence for at least 12 weeks during the first 24 weeks. The study uses questionnaires and clinical assessments to measure fatigue and quality of life.

This research aims to collect long-term safety and efficacy data for participants who have been using bomedemstat and are benefiting from it, or have achieved blood count remission in certain conditions. The study includes individuals with essential thrombocythemia ET, polycythemia vera PV, and myelofibrosis MF who have previously been in earlier bomedemstat trials. It does not involve hypothesis testing but focuses on extended monitoring. Participants will take oral bomedemstat capsules once daily for up to 10 years. The dose they start with will be the same as they used in their previous study before transitioning into this extension. This allows continuous assessment of the effects and safety of the medication over a long period. During the study, participants will be closely monitored for adverse events and any reasons for stopping treatment due to side effects. For those with ET or PV, the duration of their clinical response and remission will be tracked, as well as any progression to more severe conditions. Other outcomes include the frequency of blood clots and bleeding events. Participant involvement may last up to about 10 years, with regular assessments and safety checks throughout.

Researchers are evaluating treatments for community-acquired pneumonia CAP, especially in patients admitted to intensive care units ICUs. This trial also adapts to study treatments for respiratory pandemics like COVID-19. The goal is to determine which treatment strategies improve outcomes for patients with severe pneumonia, using a flexible, ongoing approach that can test multiple therapies simultaneously and update as new information becomes available. Participants receive different treatment strategies based on random assignment to study groups. Treatments include various antibiotics, steroids, antivirals, immune modulators, anticoagulation methods, and ventilation strategies. Some treatment options have been closed to recruitment, reflecting the trials adaptive nature. The trial includes several domains targeting specific infections such as influenza and COVID-19, with dosing and duration guided by clinical practice and local guidelines. During the study, participants are monitored closely with assessments including survival up to 90 days, days alive without organ support in ICU, ICU and hospital length of stay, ventilator-free days, organ failure-free days, and quality of life up to 6 months. Researchers collect detailed data on patient outcomes, organ support needs, and hospital discharge status. The study runs until February 2028, with ongoing evaluation to improve pneumonia treatment strategies in ICU settings and during respiratory pandemics.

Researchers are studying whether adding navtemadlin to ruxolitinib treatment can provide more benefit than ruxolitinib alone for adults with Myelofibrosis who have not responded well to ruxolitinib by itself. This Phase 3 trial includes patients who are new to JAK inhibitor treatment and have a confirmed diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia Myelofibrosis. The study aims to assess improvements in spleen size and symptom reduction over 24 weeks, as well as long-term outcomes like disease progression and overall survival. Participants first receive ruxolitinib alone during a run-in period to identify those with suboptimal response. Those qualifying are randomly assigned in a 21 ratio to receive either navtemadlin or a placebo as an add-on to their ongoing ruxolitinib. Navtemadlin or placebo is taken orally once daily for 7 days followed by 21 days off in 28-day cycles, while ruxolitinib is taken twice daily continuously. The study is double-blinded so neither participants nor researchers know which add-on treatment is given. During the trial, participants will undergo evaluations including spleen volume measurements and symptom assessments at 24 weeks. They will be monitored for disease progression and survival for up to 8 years. The study includes regular check-ups to track side effects, treatment adherence, and overall health status. These detailed assessments help researchers understand the potential benefits and safety of adding navtemadlin for patients with Myelofibrosis.

Researchers are evaluating the efficacy and safety of givinostat compared to hydroxyurea in patients with high-risk polycythemia vera PV who have the JAK2V617F mutation. PV is a chronic blood disorder that increases the risk of blood clots, progression to myelofibrosis, and transformation into acute leukemia. Patients aged 60 or older or those with a prior thrombotic event are considered high risk. Current treatments with hydroxyurea often do not fully control symptoms or long-term risks. Participants will be randomly assigned to receive either oral givinostat at 50 mg twice daily or hydroxyurea at 500 mg twice daily for 48 weeks. Dosages may be adjusted based on side effects or lack of effectiveness. After this core treatment phase, eligible patients can enter an extended treatment phase to receive long-term givinostat, allowing collection of additional safety and efficacy data. Throughout the study, participants will have regular visits to monitor blood counts, spleen size, and treatment responses. Researchers will assess the proportion of patients achieving a response at week 48, including complete hematological response and spleen size normalization. Safety and tolerability will be evaluated up to week 48. The study aims to collect comprehensive data on treatment effects and patient outcomes over time.

The trial investigates the role of ixazomib in patients with relapsed multiple myeloma who have previously undergone autologous stem cell transplant ASCT. It is a phase III, randomized, controlled, multi-center, open-label study aiming to assess whether adding a proteasome inhibitor to salvage ASCT conditioning improves depth of response and how consolidation and maintenance therapy influence the durability of response. The study also evaluates overall survival, progression-free survival, response rates, minimal residual disease, toxicity, and quality of life. Participants first receive re-induction therapy with 4 to 6 cycles of ixazomib, thalidomide, and dexamethasone ITD, each cycle lasting 28 days. Those achieving at least stable disease are randomly assigned to receive either conventional ASCT using melphalan alone or augmented ASCT combining melphalan with ixazomib. After ASCT, participants with minimal response or better are further randomized to either receive consolidation with 2 cycles of ITD followed by ixazomib maintenance until disease progression or no further treatment. During the study, participants undergo regular assessments including response evaluation 100 days post-ASCT, monitoring of progression-free survival for up to 120 months, and measurement of minimal residual disease at several time points. Safety and toxicity are closely monitored throughout re-induction, post-ASCT, consolidation, and maintenance phases. Quality of life questionnaires are completed at baseline, post-re-induction, post-ASCT, and during follow-up visits up to 24 months. The study plans to register 406 participants, with 284 randomized at the first stage and 248 at the second stage.

Researchers are studying patients with newly diagnosed stage I, II, and III colorectal cancer CRC to understand how circulating tumor DNA ctDNA in the blood can predict disease relapse. The study evaluates whether using ctDNA to guide adjuvant chemotherapy decisions after surgery is as effective as standard chemotherapy, aiming to reduce unnecessary treatments and side effects. This multi-center, prospective research includes both observational and randomized components to better manage early-stage CRC. The study has two parts Part B focuses on collecting tumor tissue, serial blood samples, and clinical data to detect minimal residual disease MRD using ctDNA after curative surgery. Part C is a randomized trial comparing ctDNA-guided adjuvant chemotherapy versus standard care in patients with high-risk stage II or III CRC. Patients are randomized post-surgery to either standard chemotherapy or a ctDNA-guided approach where those testing negative for ctDNA may receive less chemotherapy. Participants will undergo regular blood sampling and clinical assessments to monitor ctDNA levels and disease status. Researchers will measure outcomes such as 3-year disease-free survival and the relationship between ctDNA detection and treatment response over several years. The study includes follow-up periods of 4 to 8 years to evaluate long-term outcomes and safety. Participants need to consent, adhere to follow-up schedules, and be suitable for chemotherapy if randomized to Part C.