Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Placebo-controlled

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm 1
Navtemadlin administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.
  • Drug: Navtemadlin
    Navtemadlin is an investigational MDM2 inhibitor
    Other names:
    • KRT-232
  • Drug: Ruxolitinib
    Ruxolitinib is a janus kinase 1/2 inhibitor
    Other names:
    • Jakafi
    • Jakavi
Active Comparator
Arm 2
Navtemadlin placebo administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.
  • Drug: Navtemadlin placebo
    Navtemadlin placebo
    Other names:
    • KRT-232
  • Drug: Ruxolitinib
    Ruxolitinib is a janus kinase 1/2 inhibitor
    Other names:
    • Jakafi
    • Jakavi

Recruiting Locations

UAB Hospital
Birmingham 4049979, Alabama 4829764 35233

More Details

Status
Recruiting
Sponsor
Kartos Therapeutics, Inc.

Study Contact

John Mei
650-542-0136
jmei@kartosthera.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.