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
Primary Purpose
Myelofibrosis
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KRT-232
Ruxolitinib
Sponsored by
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring navtemadlin
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
Sites / Locations
- City of HopeRecruiting
- John Hopkins UniversityRecruiting
- University of MichiganRecruiting
- Icahn School of Medicine at Mount SinaiRecruiting
- Cleveland ClinicRecruiting
- Fox Chase Cancer CenterRecruiting
- MD Anderson Cancer CenterRecruiting
- Fred Hutchinson Cancer Research CenterRecruiting
- Royal Adelaide HospitalRecruiting
- Dr. Georgi StranskiRecruiting
- Saint Ivan Rilski HospitalRecruiting
- University Mutiprofile Hospital AlexandrovskaRecruiting
- CHU de CaenRecruiting
- Chu AngersRecruiting
- Centre Hospitalier du MansRecruiting
- Institut Paoli-CalmettesRecruiting
- CHU Saint EloiRecruiting
- Hopital Saint LouisRecruiting
- CHU Tours - Hôpital BretonneauRecruiting
- Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und StammzelltransplantationRecruiting
- Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/OnkologieRecruiting
- Universitaetsklinikum JenaRecruiting
- UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und PoliklinikRecruiting
- Stauferklinikum Schwäbisch GmündRecruiting
- Shamir Medical Center ( Assaf Harofeh)Recruiting
- Bologna University Hospital, Institute of HematologyRecruiting
- Universita degli Studi di CataniaRecruiting
- University of FlorenceRecruiting
- Istituto Tumori della Romagna (IRST)Recruiting
- Ospedale di Circolo e Fondazione MacchiASST Sette LaghiRecruiting
- Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w KrakowieRecruiting
- Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny HematologiiRecruiting
- d'Hebron University Hospital in BarcelonaRecruiting
- Hospital Universitario Germans Trias i PujolRecruiting
- Hospital Universitario de Gran Canaria Doctor NegrinRecruiting
- Hospital Virgen de la VictoriaRecruiting
- Hospital Universitario de SalamancaRecruiting
- Hospital de Dia Quiron ZaragozaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Part A, Arm 1, Cohort 1
Arm Description
KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
Outcomes
Primary Outcome Measures
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.
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
Secondary Outcome Measures
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)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04485260
Brief 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
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
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 28, 2021 (Actual)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kartos Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelofibrosis
Keywords
navtemadlin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A, Arm 1, Cohort 1
Arm Type
Experimental
Arm Description
KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
Intervention Type
Drug
Intervention Name(s)
KRT-232
Intervention Description
administered by mouth
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi, Jakavi
Intervention Description
administered by mouth
Primary Outcome Measure Information:
Title
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
Description
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.
Time Frame
15 months
Title
For Phase 2:To determine the spleen volume reduction (SVR) at Week 24
Description
The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan
Time Frame
6 months after last patient enrolled
Secondary Outcome Measure Information:
Title
To determine spleen response
Description
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)
Time Frame
43 months
Title
To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
Description
The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study
Time Frame
43 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Mei
Phone
650-542-0136
Email
jmei@kartosthera.com
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
John Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Name
Royal Adelaide Hospital
City
Adelaide
Country
Australia
Individual Site Status
Recruiting
Facility Name
Dr. Georgi Stranski
City
Pleven
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Saint Ivan Rilski Hospital
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
University Mutiprofile Hospital Alexandrovska
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
CHU de Caen
City
Caen
State/Province
Cedex 9
ZIP/Postal Code
14033
Country
France
Individual Site Status
Recruiting
Facility Name
Chu Angers
City
Angers
ZIP/Postal Code
49933
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier du Mans
City
Le Mans
ZIP/Postal Code
72000
Country
France
Individual Site Status
Recruiting
Facility Name
Institut Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Saint Eloi
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Saint Louis
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Tours - Hôpital Bretonneau
City
Tours
Country
France
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Individual Site Status
Recruiting
Facility Name
Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie
City
Halle
ZIP/Postal Code
6120
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Jena
City
Jena
Country
Germany
Individual Site Status
Recruiting
Facility Name
UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Recruiting
Facility Name
Stauferklinikum Schwäbisch Gmünd
City
Mutlangen
ZIP/Postal Code
73557
Country
Germany
Individual Site Status
Recruiting
Facility Name
Shamir Medical Center ( Assaf Harofeh)
City
Zerifin
ZIP/Postal Code
7033001
Country
Israel
Individual Site Status
Recruiting
Facility Name
Bologna University Hospital, Institute of Hematology
City
Bologna
ZIP/Postal Code
340136
Country
Italy
Individual Site Status
Recruiting
Facility Name
Universita degli Studi di Catania
City
Catania
ZIP/Postal Code
95124
Country
Italy
Individual Site Status
Recruiting
Facility Name
University of Florence
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Tumori della Romagna (IRST)
City
Meldola
ZIP/Postal Code
47014
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ospedale di Circolo e Fondazione MacchiASST Sette Laghi
City
Varese
ZIP/Postal Code
21100
Country
Italy
Individual Site Status
Recruiting
Facility Name
Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie
City
Kraków
Country
Poland
Individual Site Status
Recruiting
Facility Name
Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii
City
Opole
Country
Poland
Individual Site Status
Recruiting
Facility Name
d'Hebron University Hospital in Barcelona
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Germans Trias i Pujol
City
Barcelona
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario de Gran Canaria Doctor Negrin
City
Las Palmas De Gran Canaria
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Virgen de la Victoria
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital de Dia Quiron Zaragoza
City
Zaragoza
ZIP/Postal Code
50012
Country
Spain
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
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
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