Study on the Safety and Effectiveness of Navtemadlin and Ruxolitinib for Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

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What is this study about?

This clinical trial is focused on studying the safety and effectiveness of a new treatment combination for patients with certain types of blood disorders. The diseases being studied are Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, and Post-Essential Thrombocythemia Myelofibrosis. These are conditions where the bone marrow, which is responsible for producing blood cells, does not function properly. The treatment being tested combines two medications: Navtemadlin (also known by its code name KRT-232 or AMG 232) and Ruxolitinib. Both medications are taken orally in tablet form.

The purpose of the study is to determine the best dose of KRT-232 when used with Ruxolitinib and to see if this combination can reduce the size of the spleen, an organ that can become enlarged in these conditions. The study will involve regular check-ups and assessments to monitor the safety and effectiveness of the treatment. Participants will take the medications and have their spleen size measured at various points during the study, including at the 24-week mark. The study will also look at other factors, such as changes in symptoms and the need for blood transfusions.

This trial is open-label, meaning both the researchers and participants know which treatment is being administered. The study is expected to continue until 2025, allowing researchers to gather comprehensive data on the treatment’s impact over time. Participants will be closely monitored for any side effects or changes in their condition throughout the study period.

1 initial assessment

Upon joining the study, an initial assessment is conducted to confirm eligibility. This includes a review of medical history and a physical examination.

An MRI or CT scan is performed to measure spleen volume, which must be done no more than 14 days before the first dose of KRT-232.

2 medication administration

The study involves the administration of two medications: navtemadlin (also known as KRT-232) and ruxolitinib. Both are taken orally in tablet form.

The dosage of navtemadlin varies between 10-60 mg or 25-60 mg, depending on the specific requirements of the study phase.

The dosage of ruxolitinib is determined based on prior treatment and is taken consistently throughout the study.

3 ongoing monitoring

Regular monitoring is conducted to assess the safety and effectiveness of the treatment. This includes physical examinations, laboratory tests, and imaging studies.

The primary goal is to determine the optimal dose of KRT-232 in combination with ruxolitinib and to evaluate the reduction in spleen volume at Week 24.

4 evaluation of treatment response

The response to treatment is evaluated by measuring changes in spleen size and symptom scores.

The study aims to achieve a reduction in spleen volume of at least 35% from baseline, as assessed by MRI or CT scan.

5 completion of study

The study is expected to conclude by April 2025. Upon completion, a final assessment is conducted to evaluate overall health and treatment outcomes.

Participants are advised to continue using effective contraception for a specified period after the last dose of the study drug.

Who Can Join the Study?

Adults over 18 years of age.
Must have a confirmed diagnosis of one of the following conditions: 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 have been treated with a medication called ruxolitinib for at least 18 weeks before joining the study and should be on a stable dose for 8 weeks before approval to join.
The spleen, an organ in the body, must be enlarged to at least 5 cm below a certain point in the abdomen or have a volume of at least 450 cm³ as measured by an MRI or CT scan.
Must have at least 2 symptoms related to the condition, with a score of at least 1 on a specific symptom assessment form called MFSAF v4.0.
An MRI or CT scan to measure the spleen’s size must be done no more than 14 days before the first dose of the study medication, KRT-232.
Must have an ECOG performance status of 0 to 2, which is a scale used to assess how well a person can perform daily activities.
Must have adequate function of blood, liver, and kidney organs, as defined by the study protocol, within 28 days before the first dose of KRT-232.
If female and able to have children, or if male with a female partner who can have children, must use effective birth control during the study. Females must continue using birth control for 1 month and 1 week after the last dose, and males for 3 months and 1 week after the last dose.

Who Cannot Join the Study?

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Azienda Ospedaliero Universitaria Careggi	Florence	Italy

Other Sites

Site Name	City	Country
Azienda Ospedaliera S Maria Di Terni	Terni	Italy
Centre Hospitalier Le Mans	Le Mans	France
Centre Hospitalier Universitaire De Montpellier	Montpellier	France
Azienda Socio Sanitaria Territoriale Dei Sette Laghi	Varese	Italy
Isdtpeaz Rrutnnfgs Pad La Smxewb Djm Twdkby Dbav Akohoql Irgk Slgffw	Meldola	Italy
Csqnvv Hzvjufhiwra Rbjerwml Ukriapevupolp Da Tbwbg	Tours	France
Aapwcnu Ohqepugtowe Uanbgegkfzqcq Cdsqjkgbscds Dztni Smlpdd E Djhbt Suwcebu Dc Thxnvx	Turin	Italy
Cayjfq Higsdnmbubz Rzoblykn Dnzctudivqqnuq	Angers	France

Trial status

Country	Status	Recruitment Start
France	Not recruiting	01.09.2020
Italy	Not recruiting	01.09.2020

Trial locations

Investigated drugs:

KRT-232 is an investigational medication being studied for its potential to help patients with certain types of myelofibrosis, a condition where scar tissue forms in the bone marrow and affects blood cell production. It is being tested to see if it can improve the effectiveness of another medication, ruxolitinib, in patients who have not had a sufficient response to ruxolitinib alone.

Ruxolitinib is a medication that is already used to treat myelofibrosis. It works by blocking certain enzymes in the body that are involved in the overproduction of blood cells. This can help reduce symptoms and improve quality of life for patients with myelofibrosis. In this study, ruxolitinib is being combined with KRT-232 to see if the combination can provide better results for patients.

Primary Myelofibrosis – This is a disorder where the bone marrow is replaced by fibrous tissue, leading to a decrease in blood cell production. Over time, this can cause symptoms like fatigue, weakness, and an enlarged spleen. The disease progresses as the bone marrow becomes increasingly fibrotic, reducing its ability to produce blood cells. This can lead to anemia, increased risk of bleeding, and infections due to low blood cell counts. The spleen may enlarge as it tries to compensate for the lack of blood cell production in the bone marrow.

Post-Polycythemia Vera Myelofibrosis – This condition occurs in some individuals who have had polycythemia vera, a disease where the body produces too many red blood cells. Over time, the bone marrow becomes scarred, leading to a decrease in blood cell production. Symptoms may include fatigue, weight loss, and an enlarged spleen. As the disease progresses, the bone marrow’s ability to produce blood cells diminishes, causing anemia and other blood-related issues. The spleen may enlarge further as it attempts to produce blood cells.

Post-Essential Thrombocythemia Myelofibrosis – This disease develops in some individuals who have had essential thrombocythemia, a condition characterized by an overproduction of platelets. Over time, the bone marrow becomes fibrotic, reducing its ability to produce blood cells. Symptoms can include fatigue, night sweats, and an enlarged spleen. As the disease progresses, blood cell production decreases, leading to anemia and other complications. The spleen may become significantly enlarged as it tries to compensate for the reduced blood cell production.

Trial ID:

2024-514468-26-00

Protocol code:

KRT-232-109

Trial Phase:

Human Pharmacology (Phase I) – Other

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Study on the Safety and Effectiveness of Navtemadlin and Ruxolitinib for Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

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