Recruiting NCT06479135

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

Phase III Interventional Myelofibrosis Post-PV MF Post-ET Myelofibrosis Primary Myelofibrosis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Navtemadlin, Navtemadlin placebo, Ruxolitinib.
Who it may be relevant to: Registry conditions: Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Austria, Belgium, Croatia +14
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

Overview

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.

Interventions

Drug Navtemadlin
Navtemadlin is an investigational MDM2 inhibitor
Drug Navtemadlin placebo
Navtemadlin placebo
Drug Ruxolitinib
Ruxolitinib is a janus kinase 1/2 inhibitor

Primary outcome measures

To compare spleen volume reduction (SVR35) between Arm 1 and Arm 2 [Time frame: 24 weeks]
To compare total symptom score reduction (TSS50) between Arm 1 and Arm 2 [Time frame: 24 weeks]

Secondary outcome measures (2)

To compare time to progression between Arm 1 and Arm 2 [Time frame: Up to 8 years]
To compare overall survival (OS) between Arm 1 and Arm 2 [Time frame: Up to 8 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment