Primary Myelofibrosis (PMF)Phase 2NCT04878003
Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
A Phase 2 study testing KRT-232 and TL-895 in people with Primary Myelofibrosis (PMF) and Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), run by Kartos Therapeutics, Inc. at 29 sites in 9 countries.
Trial summary
This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF) The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)
- What is being tested?
- KRT-232 and TL-895
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 29 sitesin 9 countries
- Study dates
- 13 Apr 2021to Oct 2025
- Phase
- Phase 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 years and older
- 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 (WHO)
- High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic System (DIPSS)
- ECOG of 0 or 1
Who cannot join
- Subjects who are positive for p53 mutation (Arm 1)
- Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1)
- Prior treatment with any JAK inhibitor
- Prior splenectomy
- Splenic irradiation within 24 weeks prior to randomization
- Prior allogeneic stem-cell transplantation or plans for allogeneic stem-cell transplant
Show all 9Show fewer
- History of major organ transplant
- Grade 2 or higher QTc prolongation
- Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization
Trial locations and contacts
29 sites in 9 countries.
29 sites in 9 countries
Russia6 sites, 6 recruiting
- Recruiting
Botkin City Clinical Hospital
Moscow, 125284
- Recruiting
Republican Hospital n.a. V.A. Baranov
Petrozavodsk, 185019
- Recruiting
Pavlov First Saint Petersburg State Medical University
Saint Petersburg, 197022
- Recruiting
Almazov National Medical Research Center
Saint Petersburg, 197341
- Recruiting
Almazov National Medical Research Centre
Saint Petersburg, 197341
- Recruiting
Samara State Medical University
Samara, 443099
Bulgaria5 sites, 5 recruiting
- Recruiting
UMHAT Georgi Stranski
Pleven, 5800
- Recruiting
Medical Centre Hipokrat N
Plovdiv, 4000
- Recruiting
UMHAT Sv. Ivan Rilski EAD
Sofia, 1431
- Recruiting
Military Medical Academy
Sofia, 1606
- Recruiting
Specialized Hospital for Active Treatment of Hematologic Diseases
Sofia, 1756
United States4 sites, 4 recruiting
- Recruiting
Gabrail Cancer Center
Canton, Ohio, 44718
- Recruiting
Innovative Clinical Research Institute
Glendale, California, 90603
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Innovative Clinical Research Institute
Whittier, California, 90603
Mexico4 sites, 4 recruiting
- Recruiting
Centro de Investigacion Medica Aquascalientes (CIMA)
Aguascalientes, 20116
- Recruiting
Unidad de Investigacion CIMA SC
Chihuahua City, 31200
- Recruiting
Centro de Investigacion Clinica de Oaxaca (CICLO)
Oaxaca City, 68020
- Recruiting
Sociedad de Metabolismo Y Corazon - SOMECO
Veracruz, 91900
Georgia3 sites, 3 recruiting
- Recruiting
JSC EVEX Hospitals
Kutaisi, 4600
- Recruiting
LTD M.Zodelava Hematology Centre
Tbilisi, 112
- Recruiting
K.Eristavi National Center of Experimental and Clinical Surgery
Tbilisi, 159
Poland3 sites, 3 recruiting
- Recruiting
Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
Katowice, 40-519
- Recruiting
Szpital Wojewodzki w Opolu Sp. z o.o., Oddzial Hematologii i Onkologii Hematologicznej
Opole, 45-061
- Recruiting
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
Słupsk, 76-200
Belarus2 sites, 2 recruiting
- Recruiting
Republican Scientific Practical Center of Radiation Medicine and Human Ecology
Belarus’, 246040
- Recruiting
Minsk Scientific and Practice Center of Surgery, Transplantology and Hematology
Minsk, 220045
South Africa1 site, 1 recruiting
- Recruiting
Wits Baragwanath Clinical Hematology Department
Soweto, 1519
Ukraine1 site, 1 recruiting
- Recruiting
City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City Council
Dnipro, 49102
About this study
Official title: An Open-Label, Multicenter, Phase 2 Study Assessing the Safety and Efficacy of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF)
The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.
- Conditions
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)
- Being tested
- KRT-232, TL-895
- 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
KRT-232, administration by mouth
TL-895Drug
TL-895, administration by mouth
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles Receives: Drug: KRT-232 |
| Arm 2 | Experimental | TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles Receives: Drug: TL-895 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spleen Volume Reduction (SVR)
The proportion of subjects achieving ≥35% SVR at Week 24 by MRI/CT (central review)
Measured: 24 weeks
Secondary outcomes (5)
Improvement in Total Symptom Score (TSS)
The proportion of subjects who have at least a 50% reduction from Baseline to Week 24 in the total symptom score as measured by the MF-SAF v4.0
Measured: 24 weeks
Spleen Response Duration
Time from initial SVR of ≥35% by MRI/CT (central review) until progression
Measured: 48 months
Rate of conversion from RBC transfusion dependent to independent
The proportion of subjects who convert from transfusion dependent to transfusion independent at Week 24
Measured: 24 weeks
Overall Survival (OS)
Time from first dose to death from any cause
Measured: 48 months
Progression free survival (PFS)
Time from randomization to either first occurrence of disease progression or death due to any cause
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2021
- Study start13 Apr 2021
- Primary completionMay 2024 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Myelofibrosis (PMF)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 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
- NCT04878003
- Sponsor's protocol ID
- KRT-232-114
- Status last verified
- May 2022
- First submitted
- 4 May 2021
- Last updated
- 9 May 2022
- Results posted
- No
- Data monitoring committee
- 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 2 Study Assessing the Safety and Efficacy of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
- ClinicalTrials.gov ID
- NCT04878003
- Acronym / sponsor ID
- KRT-232-114
- Conditions
- Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)
- Keywords
- navtemadlin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Apr 2021 (actual)
- Primary completion
- May 2024 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 7 May 2021 (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 study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF)
The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: KRT-232KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles |
| Arm 2 | Experimental | Drug: TL-895TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
- High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic System (DIPSS)
- ECOG of 0 or 1
Key exclusion criteria (9 listed)
- Subjects who are positive for p53 mutation (Arm 1)
- Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1)
- Prior treatment with any JAK inhibitor
- Prior splenectomy
- Splenic irradiation within 24 weeks prior to randomization
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-232KRT-232, administration by mouth | Drug | Arm 1 |
| TL-895TL-895, administration by mouth | Drug | Arm 2 |
Primary outcome
Spleen Volume Reduction (SVR)
Time frame: 24 weeks
The proportion of subjects achieving ≥35% SVR at Week 24 by MRI/CT (central review)
5 secondary outcomes
Improvement in Total Symptom Score (TSS)
Time frame: 24 weeks
Spleen Response Duration
Time frame: 48 months
Rate of conversion from RBC transfusion dependent to independent
Time frame: 24 weeks
Overall Survival (OS)
Time frame: 48 months
Progression free survival (PFS)
Time frame: 48 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.
29 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KRT-232 and TL-895 in people with Primary Myelofibrosis (PMF) and Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), run by Kartos Therapeutics, Inc. at 29 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 3 inclusion and 9 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 29 sites in Russia, Bulgaria, United States, Mexico, Georgia 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 phase mean?
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?
Spleen Volume Reduction (SVR) (time frame: 24 weeks). 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.