MyelofibrosisPhase 1/2NCT04485260
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
A Phase 1/2 study testing KRT-232 and Ruxolitinib in people with Myelofibrosis, run by Kartos Therapeutics, Inc. at 38 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Myelofibrosis
- What is being tested?
- KRT-232 and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 38 sitesin 9 countries
- Study dates
- 28 Jan 2021to Oct 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
38 sites in 9 countries.
38 sites in 9 countries
United States8 sites, 8 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
- Recruiting
John Hopkins University
Baltimore, Maryland, 21205
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44106
- Recruiting
City of Hope
Duarte, California, 91010
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
- Recruiting
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
France7 sites, 7 recruiting
- Recruiting
Chu Angers
Angers, 49933
- Recruiting
CHU de Caen
Caen, Cedex 9, 14033
- Recruiting
Centre Hospitalier du Mans
Le Mans, 72000
- Recruiting
Institut Paoli-Calmettes
Marseille, 13009
- Recruiting
CHU Saint Eloi
Montpellier, 34295
- Recruiting
Hopital Saint Louis
Paris
- Recruiting
CHU Tours - Hôpital Bretonneau
Tours
Spain6 sites, 6 recruiting
- Recruiting
d'Hebron University Hospital in Barcelona
Barcelona, 08035
- Recruiting
Hospital Universitario Germans Trias i Pujol
Barcelona, 08916
- Recruiting
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria
- Recruiting
Hospital Virgen de la Victoria
Málaga, 29010
- Recruiting
Hospital Universitario de Salamanca
Salamanca
- Recruiting
Hospital de Dia Quiron Zaragoza
Zaragoza, 50012
Germany5 sites, 5 recruiting
- Recruiting
Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
Aachen, 52074
- Recruiting
Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie
Halle, 6120
- Recruiting
Universitaetsklinikum Jena
Jena
- Recruiting
UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik
Mainz, 55131
- Recruiting
Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557
Italy5 sites, 5 recruiting
- Recruiting
Bologna University Hospital, Institute of Hematology
Bologna, 340136
- Recruiting
Universita degli Studi di Catania
Catania, 95124
- Recruiting
University of Florence
Florence, 50134
- Recruiting
Istituto Tumori della Romagna (IRST)
Meldola, 47014
- Recruiting
Ospedale di Circolo e Fondazione MacchiASST Sette Laghi
Varese, 21100
Bulgaria3 sites, 3 recruiting
- Recruiting
Dr. Georgi Stranski
Pleven
- Recruiting
Saint Ivan Rilski Hospital
Sofia, 1431
- Recruiting
University Mutiprofile Hospital Alexandrovska
Sofia, 1431
Poland2 sites, 2 recruiting
- Recruiting
Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie
Krakow
- Recruiting
Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii
Opole
Israel1 site, 1 recruiting
- Recruiting
Shamir Medical Center ( Assaf Harofeh)
Tsrifin, 7033001
About this study
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
- Being tested
- KRT-232, Ruxolitinib
- Keywords
- navtemadlin
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRT-232Drug
administered by mouth
RuxolitinibDrug
Also called Jakafi, Jakavi
administered by mouth
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: KRT-232; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 6 months after last patient enrolled
Secondary outcomes (2)
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)
Measured: 43 months
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
Measured: 43 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start28 Jan 2021
- Primary completionOct 2022 (estimated)
- Study completionOct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04485260
- Sponsor's protocol ID
- KRT-232-109
- Status last verified
- May 2022
- First submitted
- 21 Jul 2020
- Last updated
- 9 May 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04485260
- Acronym / sponsor ID
- KRT-232-109
- Conditions
- Myelofibrosis
- Keywords
- navtemadlin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Jan 2021 (actual)
- Primary completion
- Oct 2022 (estimated)
- Study completion
- Oct 2024 (estimated)
- First posted
- 24 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Part A, Arm 1, Cohort 1 | Experimental | Drug: KRT-232, Drug: RuxolitinibKRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KRT-232administered by mouth | Drug | Part A, Arm 1, Cohort 1 |
| RuxolitinibAlso: Jakafi, Jakaviadministered by mouth | Drug | Part A, Arm 1, Cohort 1 |
Primary outcome
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
Time frame: 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
Time frame: 6 months after last patient enrolled
The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan
2 secondary outcomes
To determine spleen response
Time frame: 43 months
To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
Time frame: 43 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
38 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KRT-232 and Ruxolitinib in people with Myelofibrosis, run by Kartos Therapeutics, Inc. at 38 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, France, Spain, Germany, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact John Mei (650-542-0136, jmei@kartosthera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib (time frame: 15 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2022.