Clinical trial NCT04485260: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib
Official title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Myelofibrosis
Keywords: navtemadlin
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-24
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in combination with ruxolitinib.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO)
* Treatment with ruxolitinib for ≥18 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to study entry
* Spleen ≥5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT
* Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0
* ECOG performance status of 0 to 2

Exclusion Criteria:

* Patients who are positive for TP53 mutations
* Documented disease progression or clinical deterioration any time while on ruxolitinib treatment
* Patients who have had a documented spleen response to ruxolitinib.
* Prior splenectomy
* Prior MDM2 inhibitor therapy or p53-directed therapy

Primary outcomes:
measure: For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
timeFrame: 15 months
measure: For Phase 2:To determine the spleen volume reduction (SVR) at Week 24
timeFrame: 6 months after last patient enrolled
Secondary outcomes:
measure: To determine spleen response
timeFrame: 43 months
measure: To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
timeFrame: 43 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Pleven
country: Bulgaria
facility: Dr. Georgi Stranski
city: Sofia
country: Bulgaria
facility: Saint Ivan Rilski Hospital
city: Sofia
country: Bulgaria
facility: University Mutiprofile Hospital Alexandrovska
city: Caen
country: France
facility: CHU de Caen
state: Cedex 9
city: Angers
country: France
facility: Chu Angers
city: Le Mans
country: France
facility: Centre Hospitalier du Mans
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Montpellier
country: France
facility: CHU Saint Eloi
city: Paris
country: France
facility: Hopital Saint Louis
city: Tours
country: France
facility: CHU Tours - Hôpital Bretonneau
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
city: Halle
country: Germany
facility: Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Mainz
country: Germany
facility: UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch Gmünd
city: Zerifin
country: Israel
facility: Shamir Medical Center ( Assaf Harofeh)
city: Bologna
country: Italy
facility: Bologna University Hospital, Institute of Hematology
city: Catania
country: Italy
facility: Universita degli Studi di Catania
city: Firenze
country: Italy
facility: University of Florence
city: Meldola
country: Italy
facility: Istituto Tumori della Romagna (IRST)
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione MacchiASST Sette Laghi
city: Kraków
country: Poland
facility: Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie
city: Opole
country: Poland
facility: Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii
city: Barcelona
country: Spain
facility: d'Hebron University Hospital in Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrin
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Zaragoza
country: Spain
facility: Hospital de Dia Quiron Zaragoza
Study officials:
References: