UPCC 43424 A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib (POIESIS)

Investigating the Addition of an Investigational Medication to Ruxolitinib for Myelofibrosis

Enrolling By Invitation
18 years or above
All
Phase 3
600 participants needed
1 Location

Brief description of study

This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone.

Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis, MF
  • Age: 18 years or above
  • Gender: All

Inclusion Criteria for Ruxolitinib Alone Period:

  • Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
  • High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • JAK-inhibitor treatment naive

Exclusion Criteria for Ruxolitinib Alone Period:

  • Prior Splenectomy
  • Splenic irradiation within 3 months prior to the first dose
  • Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
  • Eligible for Bone Marrow Transplant
  • Peripheral blood or bone marrow blast count ≥ 10 percent

Inclusion Criteria for Randomized Period:

  • PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
  • ECOG performance status of 0 to 2
  • Treatment with a stable dose of ruxolitinib
  • Suboptimal response to run-in ruxolitinib treatment

Exclusion Criteria for Randomized Period:

  • Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10^9/L
  • Peripheral blood or bone marrow blast count ≥ 10 percent

This study investigates the effects of adding an investigational medication to an existing treatment with ruxolitinib for patients with myelofibrosis. The purpose of this study is to determine if the investigational medication can provide more benefits than ruxolitinib alone for patients who have not responded well to ruxolitinib by itself.

Participants will initially receive ruxolitinib alone. Those who do not respond adequately will be randomly assigned to one of two study arms: one receiving the investigational medication in addition to ruxolitinib, and the other receiving a placebo with ruxolitinib. A placebo is an inactive substance that looks like the investigational medicine but does not contain any medicine. The study is double-blind, meaning neither the participants nor the researchers will know who is receiving the investigational medication or placebo.

  • Who can participate: Adults with confirmed myelofibrosis who have not been treated with JAK-inhibitors before and have an ECOG performance status of 0 to 2 can participate, provided they have a suboptimal response to ruxolitinib and meet specific health criteria.
  • Study details: Participants will take ruxolitinib alone at first. If they do not respond well, they will be randomized to receive either an investigational medication or a placebo alongside ruxolitinib. Randomization ensures that each participant has an equal chance of receiving the investigational medication or placebo.
Updated on 25 Sep 2025. Study ID: 24-1576
If you need assistance finding a non-cancer clinical research study or if you have any questions, please email psom-ocr@pobox.upenn.edu For Cancer trials contact Penn Medicine's Cancer Trial Navigator at: PMCancerResearch@pennmedicine.upenn.edu or 215-349-8245

Study is selecting its participants from a population, or group of people, decided on by the researchers in advance.

Contact Abramson Cancer Center Navigator