Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

NCT06479135 · tracked via the Priya Life Science UK tracker

Sponsor

Kartos Therapeutics, Inc.

Phase

Phase 3

Started

2024-06-03

Last updated

2025-09-25

Condition(s) studied

MyelofibrosisPost-PV MFPost-ET MyelofibrosisPrimary MyelofibrosisMF

Investigational drug(s) / intervention(s)

NavtemadlinNavtemadlin placeboRuxolitinib

Navtemadlin: Navtemadlin is an investigational MDM2 inhibitor

Navtemadlin placebo: Navtemadlin placebo

Ruxolitinib: Ruxolitinib is a janus kinase 1/2 inhibitor

Study summary

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

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

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

Primary outcome measure(s)

To compare spleen volume reduction (SVR35) between Arm 1 and Arm 2 — 24 weeks
The proportion of subjects in each arm with SVR35 by MRI/CT scan (central review) 24 weeks after start of the randomized period
To compare total symptom score reduction (TSS50) between Arm 1 and Arm 2 — 24 weeks
The proportion of subjects in each arm with a TSS50 by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 24 weeks after start of the randomized period

Trial sites (215)

Facility	City	Region	Status
UAB Hospital	Birmingham	Alabama	Recruiting
Banner MD Anderson Cancer Center	Gilbert	Arizona	Recruiting
Mayo Clinic - Phoenix	Phoenix	Arizona	Recruiting
UC San Diego Moores Cancer Center	La Jolla	California	Recruiting
UCLA Hematology/Oncology Clinic - Los Angeles	Los Angeles	California	Recruiting
Scripps Health, Prebys Cancer Center	San Diego	California	Recruiting
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California	Recruiting
Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado	Recruiting
Medical Oncology Hematology Consultants, PA	Newark	Delaware	Recruiting
MedStar Georgetown University Hospital, Lombardi Comprehensive Cancer Center	Washington D.C.	District of Columbia	Recruiting
Mayo Clinic - Jacksonville	Jacksonville	Florida	Recruiting
University of Miami	Miami	Florida	Recruiting
AdventHealth Cancer Institute	Orlando	Florida	Recruiting
Moffitt Cancer Center	Tampa	Florida	Recruiting
Mission Cancer + Blood	Des Moines	Iowa	Recruiting
University of Kansas Cancer Center - Westwood	Westwood	Kansas	Recruiting
Norton Cancer Institute	Louisville	Kentucky	Recruiting
Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	Recruiting
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	Recruiting
The Center for Cancer and Blood Disorders	Bethesda	Maryland	Recruiting
Dana Farber Cancer Institute	Boston	Massachusetts	Recruiting
University of Michigan Hospital	Ann Arbor	Michigan	Recruiting
Henry Ford Cancer Institute - Brigitte Harris Cancer Pavilion	Detroit	Michigan	Recruiting
Nebraska Hematology - Oncology, P.C.	Lincoln	Nebraska	Recruiting
Mohtaseb Cancer Center and Blood Disorders	Henderson	Nevada	Recruiting
Hackensack University Medical Center	Hackensack	New Jersey	Recruiting
Brookdale University Hospital and Medical Center	Brooklyn	New York	Recruiting
Cayuga Cancer Center	Ithaca	New York	Recruiting
Northwell Health, R.J. Zuckerberg Cancer Center	Lake Success	New York	Recruiting
ICAHN School of Medicine at Mount Sinai	New York	New York	Recruiting
Montefiore Einstein Comprehensive Cancer Center	The Bronx	New York	Recruiting
Medical University of South Carolina (MUSC)	Charleston	North Carolina	Recruiting
Atrium Health Levine Cancer Institute	Charlotte	North Carolina	Recruiting
Duke University Medical Center	Durham	North Carolina	Recruiting
Regional Medical Oncology Center	Wilson	North Carolina	Recruiting
Atrium Health Wake Forest Baptist	Winston-Salem	North Carolina	Recruiting
Gabrail Cancer Center	Canton	Ohio	Recruiting
University of Cincinnati Medical Center	Cincinnati	Ohio	Recruiting
Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio	Recruiting
Cleveland Clinic	Cleveland	Ohio	Recruiting

+ 175 more sites — see the full list on the official registry below.

On this site

📄 Jakafi (ruxolitinib) drug profile →

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Other trials for the same condition

A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib Recruiting

A Phase 1 Study of AJ1-11095 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i) Recruiting

Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis Active, not recruiting

A Study of Elritercept Alone or Together With Ruxolitinib in Adults With Myelofibrosis Recruiting

A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis Active, not recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06479135 on ClinicalTrials.gov ↗ ← All trials in the UK