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

Myelofibrosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04485260
• Other study ID #: KRT-232-109
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 28, 2021
• Est. completion date: October 2024

Study information

• Verified date: May 2022
• Source: Kartos Therapeutics, Inc.
• Contact: John Mei
• Phone: 650-542-0136
• Email: jmei[@]kartosthera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: October 2024
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Myelofibrosis
• Polycythemia
• Polycythemia Vera
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• KRT-232
administered by mouth
• Ruxolitinib
administered by mouth

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Bulgaria	Dr. Georgi Stranski	Pleven
Bulgaria	Saint Ivan Rilski Hospital	Sofia
Bulgaria	University Mutiprofile Hospital Alexandrovska	Sofia
France	Chu Angers	Angers
France	CHU de Caen	Caen	Cedex 9
France	Centre Hospitalier du Mans	Le Mans
France	Institut Paoli-Calmettes	Marseille
France	CHU Saint Eloi	Montpellier
France	Hopital Saint Louis	Paris
France	CHU Tours - Hôpital Bretonneau	Tours
Germany	Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation	Aachen
Germany	Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie	Halle
Germany	Universitaetsklinikum Jena	Jena
Germany	UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik	Mainz
Germany	Stauferklinikum Schwäbisch Gmünd	Mutlangen
Israel	Shamir Medical Center ( Assaf Harofeh)	Zerifin
Italy	Bologna University Hospital, Institute of Hematology	Bologna
Italy	Universita degli Studi di Catania	Catania
Italy	University of Florence	Firenze
Italy	Istituto Tumori della Romagna (IRST)	Meldola
Italy	Ospedale di Circolo e Fondazione MacchiASST Sette Laghi	Varese
Poland	Oddzial Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie	Kraków
Poland	Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii	Opole
Spain	d'Hebron University Hospital in Barcelona	Barcelona
Spain	Hospital Universitario Germans Trias i Pujol	Barcelona
Spain	Hospital Universitario de Gran Canaria Doctor Negrin	Las Palmas De Gran Canaria
Spain	Hospital Virgen de la Victoria	Málaga
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital de Dia Quiron Zaragoza	Zaragoza
United States	University of Michigan	Ann Arbor	Michigan
United States	John Hopkins University	Baltimore	Maryland
United States	Cleveland Clinic	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  France,  Germany,  Israel,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib	Dose limiting toxicities will be used to establish the MTD of KRT-232 in combination with ruxolitinib. Subsequently, RP2D will be based on safety and efficacy data of the combination.	15 months
Primary	For Phase 2:To determine the spleen volume reduction (SVR) at Week 24	The proportion of subjects achieving SVR of = 35% at Week 24 by MRI/CT scan	6 months after last patient enrolled
Secondary	To determine spleen response	The proportion of subjects achieving =35% SVR at any time point from Baseline while on study, as assessed by MRI (or by CT scan for applicable subjects)	43 months
Secondary	To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)	The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study	43 months