Study of KRT-232 Combined with Ruxolitinib for Myelofibrosis Patients

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    What is this study about?

    This here clinical trial is looking at a new drug called KRT-232 that’s taken by mouth. The study aims to see if combining KRT-232 with the existing drug ruxolitinib can help folks with myelofibrosis who ain’t responding well enough to just taking ruxolitinib alone.

    The main goal in the first part of the study is to find the right dose of KRT-232 to use when combined with ruxolitinib. They’ll be looking closely at any side effects to make sure the dose is safe. In the second part, they’ll check if the combination of the two drugs can shrink the size of the spleen by at least 35% after 6 months of treatment.

    Learn more about this Trial

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      Locations

      Where does the clinical trial take place?

      Pleven , Bulgaria

      Sofia , Bulgaria

      Sofia , Bulgaria

      Caen , France

      Angers , France

      Le Mans , France

      Marseille , France

      Montpellier , France

      Paris , France

      Tours , France

      Aachen , Germany

      Halle , Germany

      Jena , Germany

      Mainz , Germany

      Mutlangen , Germany

      Bologna , Italy

      Catania , Italy

      Firenze , Italy

      Meldola , Italy

      Varese , Italy

      Kraku00f3w , Poland

      Opole , Poland

      Barcelona , Spain

      Barcelona , Spain

      Las Palmas De Gran Canaria , Spain

      Mu00e1laga , Spain

      Salamanca , Spain

      Zaragoza , Spain

      You can join this study in:

      Study Steps

      How Complex Will My Study Be and What Phases Will I Go Through?

      Based on the information provided about this clinical trial, here are the key steps a patient would need to take:

      1. Patients will receive the study drug KRT-232 by mouth once daily on Days 1-7 of each 28-day cycle. They will be off treatment on Days 8-28 of each cycle.
      2. Patients will also continue to take Ruxolitinib (Jakafi/Jakavi) by mouth during the study period. They need to have been on a stable dose of Ruxolitinib for at least 8 weeks prior to starting the study.
      3. The study plans to enroll patients for approximately 15 months for the Phase 1 portion to determine the recommended Phase 2 dose of KRT-232 in combination with Ruxolitinib.
      4. The Phase 2 portion will evaluate spleen volume reduction after 24 weeks, with final study completion planned approximately 43 months after enrolling the last patient.

      So in summary, eligible patients will take KRT-232 for 7 days on and 21 days off in 28-day cycles, along with continuing their current stable dose of Ruxolitinib, over a period that could last up to around 3.5 years depending on when they enroll in the study. The exact number of treatment cycles would depend on each individual patient’s response and tolerability.


      Diseases Under Investigation

      What Conditions Qualify Me for This Study?

      Based on the eligibility criteria, you need to have one of the following diseases to join the study:

      1. Primary Myelofibrosis (PMF): A rare bone marrow disorder that disrupts your body’s normal production of blood cells. The result is extensive scarring in your bone marrow, leading to severe anemia, weakness, fatigue, and often, an enlarged spleen and liver.
      2. Post-Polycythemia Vera Myelofibrosis (Post-PV MF): A condition that may occur in some patients previously diagnosed with polycythemia vera (PV), a blood cancer where the bone marrow makes too many red blood cells. Over time, PV can evolve into a more serious form of myelofibrosis.
      3. Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF): A condition that may develop in some patients previously diagnosed with essential thrombocythemia (ET), a disorder where the body produces too many platelets. In some cases, ET can progress to myelofibrosis.

      The diagnosis must be confirmed by the treating physician according to the World Health Organization (WHO) criteria. Other eligibility criteria related to your medical condition, treatment history, and overall health status also apply.


      Terms and conditions

      What Requirements I Have to Meet To Join This Study?

      When Am I Eligible to Join the Study?

      To join this study, you must meet the following inclusion criteria:

      1. Confirmed diagnosis of myelofibrosis, which includes:
        • Primary myelofibrosis (PMF)
        • Post-polycythemia vera myelofibrosis (post-PV MF): myelofibrosis that develops after having polycythemia vera, a condition where the body makes too many red blood cells
        • Post-essential thrombocythemia myelofibrosis (post-ET MF): myelofibrosis that develops after having essential thrombocythemia, a condition where the body makes too many platelets

        The diagnosis must be assessed by the treating physician according to World Health Organization (WHO) criteria.

      2. Prior treatment with ruxolitinib (a medication used to treat myelofibrosis) for at least 18 weeks before entering the study, and on a stable dose of ruxolitinib for 8 weeks prior to study entry
      3. Enlarged spleen, defined as a spleen measuring at least 5 cm below the left lower costal margin (the lower edge of the rib cage on the left side) or a spleen volume of at least 450 cm3 as measured by MRI or CT scan
      4. Presence of myelofibrosis symptoms: Patients must have at least 2 symptoms with a score of at least 1 on the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0), a questionnaire used to assess symptom severity in myelofibrosis
      5. ECOG performance status of 0 to 2: The ECOG (Eastern Cooperative Oncology Group) performance status is a scale used to assess how a patient’s disease is progressing and how the disease affects the patient’s daily living abilities. It ranges from 0 (fully active, able to carry on all pre-disease activities without restriction) to 5 (dead).

      What Reasons Could Exclude Me from the Study?

      Here is a list of the main exclusion criteria for this study, with explanations of medical terms:

      1. Patients who are positive for TP53 mutations
        • TP53 is a gene that helps control cell growth and division. Mutations in this gene are associated with some cancers. Patients with these mutations are excluded.
      2. Documented disease progression or clinical deterioration any time while on ruxolitinib treatment
        • Disease progression means the myelofibrosis has gotten worse while taking ruxolitinib. Clinical deterioration means the patient’s symptoms and overall health have worsened on the medication. Patients with either are excluded.
      3. Patients who have had a documented spleen response to ruxolitinib
        • A spleen response means ruxolitinib has reduced the size of the patient’s enlarged spleen. This study is for patients who have not had an adequate spleen response to ruxolitinib alone.
      4. Prior splenectomy
        • A splenectomy is surgical removal of the spleen. Patients who have already had their spleen removed are excluded, as change in spleen size is a key outcome being measured.
      5. Prior MDM2 inhibitor therapy or p53-directed therapy
        • MDM2 inhibitors are a type of drug that activate the p53 gene to suppress tumor growth. p53-directed therapies work similarly. Prior use of these therapies excludes patients from the study, which is testing a new p53-activating drug.

      Investigational Medicinal Product

      What Products Are Being Used in This Study?

      Here is a list of the drugs involved in the study:

      1. KRT-232 (navtemadlin): An investigational drug being studied in combination with ruxolitinib. KRT-232 is administered orally (by mouth) once daily for 7 days, followed by 21 days off treatment in 28-day cycles. The study aims to determine the recommended phase 2 dose (RP2D) of KRT-232 when combined with ruxolitinib.
      2. Ruxolitinib (Jakafi, Jakavi): An approved medication for the treatment of myelofibrosis. Ruxolitinib is administered orally. Patients in the study must have been treated with ruxolitinib for at least 18 weeks prior to study entry and be on a stable dose for 8 weeks before joining the trial. The study is evaluating the safety and efficacy of combining KRT-232 with ruxolitinib in patients who have had a suboptimal response to ruxolitinib alone.

      Have the Medicinal Substances Used in the Trial Been Previously Studied in Medicine?

      1. KRT-232: as an investigational drug, it is likely not well established in medical literature yet.
      2. Ruxolitinib (Jakafi, Jakavi): Ruxolitinib is an already approved medication for myelofibrosis. It is a known and established treatment in medicine and the medical literature for this condition.

      Study ID

      CT-EU-00116279

      Recruitment status

      Recruting new patients

      Start of the trial

      3 years ago