Clinical trial NCT06479135: Study of Navtemadlin Add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Myelofibrosis
Post-PV MF
Post-ET Myelofibrosis
Primary Myelofibrosis
MF
Keywords: Navtemadlin
KRT-232
Ruxolitinib
POIESIS
TP53
Suboptimal response
Sub-optimal response
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-28
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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

Primary outcomes:
measure: To compare spleen volume reduction (SVR35) between Arm 1 and Arm 2
timeFrame: 24 weeks
measure: To compare total symptom score reduction (TSS50) between Arm 1 and Arm 2
timeFrame: 24 weeks
Secondary outcomes:
measure: To compare time to progression between Arm 1 and Arm 2
timeFrame: Up to 8 years
measure: To compare overall survival (OS) between Arm 1 and Arm 2
timeFrame: Up to 8 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants, PA
state: Delaware
city: Des Moines
country: United States
facility: Mission Cancer + Blood
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Lincoln
country: United States
facility: Nebraska Hematology - Oncology, P.C.
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Einstein Comprehensive Cancer Center
state: New York
city: Brooklyn
country: United States
facility: Brookdale University Hospital and Medical Center
state: New York
city: Ithaca
country: United States
facility: Cayuga Cancer Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center at Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Independence
country: United States
facility: Independence Family Health Center - Cleveland Clinic
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital - Cleveland Clinic
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: U.T. MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Oncology Associates - Virginia Beach
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC - Tacoma
state: Washington
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Clayton
country: Australia
facility: Monash Medical Center Clayton
city: Douglas
country: Australia
facility: Townsville University Hospital
city: Gosford
country: Australia
facility: Gosford Hospital
city: Kogarah
country: Australia
facility: St George Hospital
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital - Peter MacCallum Cancer Center
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Campus Gasthuisberg
city: Roeselare
country: Belgium
facility: General Hospital Delta
city: Yvoir
country: Belgium
facility: UCL Mont-Godinne University Hospitals
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre Rijeka
city: Sibenik
country: Croatia
facility: General Hospital of Sibenik-Knin County
city: Split
country: Croatia
facility: University Hospital of Split
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
city: Zagreb
country: Croatia
facility: Clinical Hospital Merkur
city: Zagreb
country: Croatia
facility: Solmed Clinic
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Kutaisi
country: Georgia
facility: JSC Vian
city: Tbilisi
country: Georgia
facility: JSC German Hospital
city: Tbilisi
country: Georgia
facility: LEPL The First University Clinic of Tbilisi State Medical University
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic LLC
city: Tbilisi
country: Georgia
facility: JSC K. Eristavi National Center of Experimental and Clinical Surgery
city: Tbilisi
country: Georgia
facility: Caucasus Medical Centre LLC
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University - Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
city: Cáceres
country: Spain
facility: Caceres Hospital Complex - San Pedro de Alcantara General Hospital
city: Las Palmas De Gran Canaria
country: Spain
facility: Gran Canaria Dr Negrin University Hospital
city: Madrid
country: Spain
facility: University Hospital 12 de Octubre
city: Madrid
country: Spain
facility: University Hospital Ramon y Cajal
city: Malaga
country: Spain
facility: University Hospital Virgen de la Victoria
city: Valencia
country: Spain
facility: University and Polytechnic Hospital La Fe
city: Zaragoza
country: Spain
facility: Quironsalud Zaragoza Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Center NHS Foundation Trust
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: Oxford
country: United Kingdom
facility: Genesis Care, Oxford
city: Windsor
country: United Kingdom
facility: Genesis Care, Windsor
Study officials:
References: