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

Phase 1

Recruiting

• Conditions: Myelofibrosis
• Interventions: Drug: KRT-232; Drug: Ruxolitinib

• Registration Number: NCT04485260
• Lead Sponsor: Kartos Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-21
• Study First Submitted QC: 2020-07-21
• Study First Posted: 2020-07-24
• Study Start: 2021-01-28
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-05
• Last Update Posted: 2022-05-09
• Primary Completion: 2022-10
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part A, Arm 1, Cohort 1	KRT-232	KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
Part A, Arm 1, Cohort 1	Ruxolitinib	KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)

Primary Outcome Measures

Name	Time	Method
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib	15 months	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.
For Phase 2:To determine the spleen volume reduction (SVR) at Week 24	6 months after last patient enrolled	The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan

Secondary Outcome Measures

Name	Time	Method
To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)	43 months	The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study
To determine spleen response	43 months	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)

Trial Locations

Locations (38)

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie; 🇵🇱 Kraków, Poland

Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii; 🇵🇱 Opole, Poland

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, Spain

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

City of Hope; 🇺🇸 Duarte, California, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

John Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Saint Ivan Rilski Hospital; 🇧🇬 Sofia, Bulgaria

CHU de Caen; 🇫🇷 Caen, Cedex 9, France

Chu Angers; 🇫🇷 Angers, France

Centre Hospitalier du Mans; 🇫🇷 Le Mans, France

CHU Saint Eloi; 🇫🇷 Montpellier, France

Hopital Saint Louis; 🇫🇷 Paris, France

CHU Tours - Hôpital Bretonneau; 🇫🇷 Tours, France

Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation; 🇩🇪 Aachen, Germany

Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie; 🇩🇪 Halle, Germany

UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik; 🇩🇪 Mainz, Germany

Universitaetsklinikum Jena; 🇩🇪 Jena, Germany

Universita degli Studi di Catania; 🇮🇹 Catania, Italy

Bologna University Hospital, Institute of Hematology; 🇮🇹 Bologna, Italy

Stauferklinikum Schwäbisch Gmünd; 🇩🇪 Mutlangen, Germany

University of Florence; 🇮🇹 Firenze, Italy

Istituto Tumori della Romagna (IRST); 🇮🇹 Meldola, Italy

Ospedale di Circolo e Fondazione MacchiASST Sette Laghi; 🇮🇹 Varese, Italy

Shamir Medical Center ( Assaf Harofeh); 🇮🇱 Zerifin, Israel

Dr. Georgi Stranski; 🇧🇬 Pleven, Bulgaria

University Mutiprofile Hospital Alexandrovska; 🇧🇬 Sofia, Bulgaria