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Study of the Safety and Efficacy of KRT-232 Combined with Ruxolitinib in Patients with Primary Myelofibrosis (PMF), Post–Polycythemia Vera MF (Post–PV-MF), Or Post–Essential Thrombocythemia MF (Post-ET-MF) Who Have a Suboptimal Response to Ruxolitinib
EU CTIS ID: 2024-514468-26-00
What this study is testing
- To determine the navtemadlin RP2D in combination with ruxolitinib - To determine the spleen volume reduction (SVR) at Week 24
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Adults >18 years of age.
- For full list please refer to the Protocol
- Confirmed diagnosis of PMF, post–PV-MF, or post–ET-MF, as assessed by treating physician according to the World Health Organization (WHO) criteria.
- Treatment with ruxolitinib for ≥ 18 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to Sponsor approval of the enrollment form.
- Spleen ≥ 5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT
- Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0
You likely can't join if
- Patients who are positive for TP53 mutations.
- Women who are pregnant or breastfeeding
- History of major organ transplant
- Subjects must be negative for HIV-1 antibody, negative for HbsAg, negative for Hepatitis B core antibody, and negative for viral RNA if HCV antibody is positive. Subjects must be negative for Hepatitis B DNA, if either HbsAg or Hepatitis B core antibody is positive.
- Active serious viral, mycobacterial, parasitic, fungal, and bacterial infections, including acute hepatitis A, herpes zoster, and progressive multifocal leukoencephalopathy (PML). Active serious infections must be resolved before screening/enrollment. Subjects with acute infections requiring systemic antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
- Patients with uncontrolled intercurrent illness including, but not limited to; clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; ventricular arrhythmia; or patients with psychiatric illness/social situations that would limit compliance with study requirements; or patients who have been committed to an institution by judicial or administrative authority.
See the full eligibility criteria
Who can join
- Adults >18 years of age.
- For full list please refer to the Protocol
- Confirmed diagnosis of PMF, post–PV-MF, or post–ET-MF, as assessed by treating physician according to the World Health Organization (WHO) criteria.
- Treatment with ruxolitinib for ≥ 18 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to Sponsor approval of the enrollment form.
- Spleen ≥ 5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT
- Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0
- An MRI or CT scan for spleen volume must be performed no more than 14 days prior to the first dose of navtemadlin.
- ECOG performance status of 0 to 2.
- Adequate hematological, hepatic, and renal organ function (as per protocol definition and within 28 days prior to the first dose of navtemadlin).
- Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential must both use an effective contraception method during the study. In addition, after the last dose of study drug, female subjects must continue to use contraception for 1 month and 1 week and male subjects must continue to use contraception for 3 months and 1 week.
What rules you out
- Patients who are positive for TP53 mutations.
- Women who are pregnant or breastfeeding
- History of major organ transplant
- Subjects must be negative for HIV-1 antibody, negative for HbsAg, negative for Hepatitis B core antibody, and negative for viral RNA if HCV antibody is positive. Subjects must be negative for Hepatitis B DNA, if either HbsAg or Hepatitis B core antibody is positive.
- Active serious viral, mycobacterial, parasitic, fungal, and bacterial infections, including acute hepatitis A, herpes zoster, and progressive multifocal leukoencephalopathy (PML). Active serious infections must be resolved before screening/enrollment. Subjects with acute infections requiring systemic antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
- Patients with uncontrolled intercurrent illness including, but not limited to; clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; ventricular arrhythmia; or patients with psychiatric illness/social situations that would limit compliance with study requirements; or patients who have been committed to an institution by judicial or administrative authority.
- Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma.
- Grade 2 or higher QTc prolongation (>480 milliseconds per NCICTCAE criteria, version 5.0).
- Active or chronic bleeding within 4 weeks prior to the first dose of navtemadlin.
- For full list please refer to the Protocol.
- Documented disease progression or clinical deterioration any time while on ruxolitinib treatment.
- Patients who have had a documented spleen response to ruxolitinib.
- Participation in another interventional clinical trial within the past 4 weeks of the first dose of navtemadlin (participation in observational studies is permitted).
- Other JAK inhibitors, except for ruxolitinib treatment; other recent/concurrent treatment such as a major surgery, chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or investigational therapy within 4 weeks or approximately 5 half-lives before the first dose of navtemadlin, whichever is shorter. Hydroxyurea is permitted up until the day prior to study Day 1 of study treatment with navtemadlin.
- Prior splenectomy.
- Splenic irradiation within 3 months prior to the first dose of navtemadlin.
- Prior allogeneic stem-cell transplantation or eligible for allogeneic stem cell transplantation
- Prior MDM2 inhibitor therapy or p53-directed therapy
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Israel
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Israel. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.