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

NCT04485260 | Unknown Phase 1 FDA Drug

• 1 other identifier: KRT-232-109
• Study Type: interventional
• Target: 36
• Locations: 9 countries
• Sites: 38

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.

Conditions

Myelofibrosis

Keywords

navtemadlin

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• To determine spleen response

  43 months

• To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)

  43 months

Study Arms (1)

Part A, Arm 1, Cohort 1

EXPERIMENTAL

KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)

Drug: KRT-232; Drug: Ruxolitinib

Interventions

KRT-232 DRUG

administered by mouth

Part A, Arm 1, Cohort 1

Ruxolitinib DRUG

administered by mouth

Also known as: Jakafi, Jakavi

Part A, Arm 1, Cohort 1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kartos Therapeutics, Inc.: lead

Study Sites (38)

City of Hope

Duarte, California, 91010, United States

RECRUITING

John Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44106, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

Royal Adelaide Hospital

Adelaide, Australia

RECRUITING

Dr. Georgi Stranski

Pleven, Bulgaria

RECRUITING

Saint Ivan Rilski Hospital

Sofia, 1431, Bulgaria

RECRUITING

University Mutiprofile Hospital Alexandrovska

Sofia, 1431, Bulgaria

RECRUITING

CHU de Caen

Caen, Cedex 9, 14033, France

RECRUITING

Chu Angers

Angers, 49933, France

RECRUITING

Centre Hospitalier du Mans

Le Mans, 72000, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

RECRUITING

CHU Saint Eloi

Montpellier, 34295, France

RECRUITING

Hopital Saint Louis

Paris, France

RECRUITING

CHU Tours - Hôpital Bretonneau

Tours, France

RECRUITING

Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation

Aachen, 52074, Germany

RECRUITING

Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie

Halle, 6120, Germany

RECRUITING

Universitaetsklinikum Jena

Jena, Germany

RECRUITING

UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik

Mainz, 55131, Germany

RECRUITING

Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

RECRUITING

Shamir Medical Center ( Assaf Harofeh)

Ẕerifin, 7033001, Israel

RECRUITING

Bologna University Hospital, Institute of Hematology

Bologna, 340136, Italy

RECRUITING

Universita degli Studi di Catania

Catania, 95124, Italy

RECRUITING

University of Florence

Florence, 50134, Italy

RECRUITING

Istituto Tumori della Romagna (IRST)

Meldola, 47014, Italy

RECRUITING

Ospedale di Circolo e Fondazione MacchiASST Sette Laghi

Varese, 21100, Italy

RECRUITING

Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie

Krakow, Poland

RECRUITING

Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii

Opole, Poland

RECRUITING

d'Hebron University Hospital in Barcelona

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Germans Trias i Pujol

Barcelona, 08916, Spain

RECRUITING

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, Spain

RECRUITING

Hospital Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, Spain

RECRUITING

Hospital de Dia Quiron Zaragoza

Zaragoza, 50012, Spain

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid; ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

John Mei

CONTACT

650-542-0136; jmei@kartosthera.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: July 24, 2020
• Study Start: January 28, 2021
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2024
• Last Updated: May 9, 2022

Record last verified: 2022-05

Locations

PL (2); DE (5); FR (7); US (8); ES (6); BU (3); AU (1); IT (5); IL (1)