This clinical trial is focused on studying a condition called myelofibrosis, which is a type of blood cancer that affects the bone marrow. The study is specifically looking at patients who have not responded well to a treatment called ruxolitinib. The trial will test the effectiveness and safety of adding a new medication called navtemadlin to the existing treatment with ruxolitinib. Navtemadlin is also known by its code name KRT-232. The study will compare the effects of navtemadlin plus ruxolitinib against a placebo plus ruxolitinib.
The purpose of the study is to see if adding navtemadlin can help reduce the size of the spleen and improve symptoms in patients with myelofibrosis. The trial will involve taking tablets of navtemadlin or a placebo along with ruxolitinib. Participants will be randomly assigned to one of the two groups, and neither the participants nor the researchers will know who is receiving the actual medication or the placebo. This is known as a double-blind study, which helps ensure the results are unbiased.
Throughout the study, participants will have regular check-ups, including physical exams and tests like MRI or CT scans, to monitor changes in spleen size and symptoms. The study will also track any side effects or adverse events that occur. The trial is expected to last several years, with the aim of providing valuable information on whether navtemadlin can offer additional benefits to patients with myelofibrosis who have a suboptimal response to ruxolitinib.
1ruxolitinib run-in period
Begin taking ruxolitinib tablets orally. The dosage will be determined by the healthcare provider based on individual needs.
This period is designed to establish a stable dose of ruxolitinib and assess the initial response to the medication.
2randomized period
Participants will be randomly assigned to one of two groups: one group will receive navtemadlin plus ruxolitinib, and the other group will receive a placebo plus ruxolitinib.
Continue taking ruxolitinib as previously prescribed. If assigned to the navtemadlin group, take navtemadlin tablets orally. The dosage will be determined by the healthcare provider.
3monitoring and assessments
Regular monitoring will occur to assess the reduction in spleen volume and symptom score. This may involve MRI or CT scans and completing the Myelofibrosis Symptom Assessment Form.
Safety assessments will include physical examinations, laboratory tests, and monitoring for any adverse events.
4end of trial
The trial is expected to conclude by May 31, 2029. At the end of the trial, final assessments will be conducted to evaluate the overall effectiveness and safety of the treatment.
Who Can Join the Study?
Must be an adult aged 18 years or older and able to give consent to participate.
Must have a confirmed diagnosis of Primary Myelofibrosis (PMF), post-Polycythemia Vera Myelofibrosis (post-PV MF), or post-Essential Thrombocythemia Myelofibrosis (post-ET MF). These are specific types of blood disorders.
Must be classified as high, intermediate-1, or intermediate-2 risk according to the International Prognosis System Score (IPSS), which is a way to assess the severity of the condition.
Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. This is a scale used to determine how well a patient can perform daily activities, with 0 being fully active and 2 being able to do some activities but not work.
Must not have been treated with a JAK-inhibitor before. JAK-inhibitors are a type of medication used to treat certain blood disorders.
For the randomized period, the condition (PMF, post-PV MF, or post-ET MF) must be TP53WT, which means a specific gene is not mutated, as confirmed by testing.
Must be on a stable dose of ruxolitinib, a medication used to treat these blood disorders.
Must have had a suboptimal response to the initial ruxolitinib therapy, meaning the treatment did not work as well as expected.
Who Cannot Join the Study?
Patients with other serious health conditions that could interfere with the study.
Patients who are pregnant or breastfeeding.
Patients who have participated in another clinical trial recently.
Patients with a history of allergic reactions to similar treatments.
Patients who are unable to follow the study procedures.
Patients with certain types of infections that are not well controlled.
Patients with severe liver or kidney problems.
Patients who have had a recent heart attack or stroke.
Patients with uncontrolled high blood pressure.
Patients with a history of certain types of cancer.
Patients who are taking medications that could interfere with the study treatment.
Patients with a history of substance abuse.
Patients with mental health conditions that could affect their ability to participate.
Patients who have had a major surgery recently.
Patients with a history of blood clotting disorders.
Navtemadlin is a medication being studied for its potential to help patients with myelofibrosis, a type of bone marrow cancer. It is being tested to see if it can reduce the size of the spleen and improve symptoms when added to another treatment.
Ruxolitinib is a medication already used to treat myelofibrosis. It works by blocking certain enzymes that contribute to the disease. In this study, it is used as a standard treatment to which other therapies are added to see if they improve patient outcomes.
Secondary Myelofibrosis – This condition occurs when scar tissue forms in the bone marrow, disrupting the production of blood cells. It can develop as a progression from other blood disorders like Polycythemia Vera or Essential Thrombocythemia. Patients may experience symptoms such as fatigue, anemia, and an enlarged spleen. Over time, the bone marrow becomes increasingly fibrotic, leading to more severe blood cell production issues. The disease can cause significant discomfort and impact daily life due to its symptoms. Monitoring and managing symptoms are crucial as the condition progresses.
Primary Myelofibrosis – This is a chronic disorder where the bone marrow is gradually replaced by fibrous tissue, leading to a decrease in blood cell production. It is characterized by symptoms such as fatigue, weakness, and an enlarged spleen. As the disease progresses, patients may experience more severe anemia and other blood-related issues. The condition can lead to significant discomfort and affect quality of life. It is a progressive disease, meaning symptoms and complications can worsen over time. Regular monitoring is important to manage the symptoms effectively.
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