AzTrials
AzTrials

MyelofibrosisPhase 1/2NCT04640532

KRT-232 in Combination With TL-895 for the Treatment of R/R MF and KRT-232 for the Treatment of JAKi Intolerant MF

A Phase 1/2 study testing KRT-232 and TL-895 in people with Myelofibrosis and Post-PV MF, run by Kartos Therapeutics, Inc. at 37 sites in 10 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This study evaluates KRT-232 in Combination With TL-895 for the Treatment of Relapsed or Refractory Myelofibrosis and KRT-232 for the Treatment of JAK Inhibitor Intolerant Myelofibrosis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis
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
116 participants
Where
37 sitesin 10 countries
Study dates
17 Nov 2020to 24 Jul 2025
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of primary MF, post-PV MF, or post-ET MF, (WHO 2016)
  • ECOG ≤ 2
  • Cohort 1 and Cohort 2: R/R following JAK inhibitor treatment
  • Cohort 3: patients who are intolerant to JAK inhibitor treatment

Who cannot join

  • Prior treatment with MDM2 inhibitors or p53-directed therapies
  • Prior treatment with a BCR-ABL, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR), bromodomain and extraterminal domain (BET), histone deacetylase (HDAC), or spleen tyrosine kinase (Syk) inhibitor
  • Prior splenectomy
  • Splenic irradiation within 3 months prior to the first dose of study treatment
  • Clinically significant thrombosis within 3 months of screening
  • Grade 2 or higher QTc prolongation

Trial locations and contacts

37 sites in 10 countries.

John Mei contact

650-542-0136

jmei@kartosthera.com

Irene Dea contact

(650) 839-7341

idea@kartosthera.com

37 sites in 10 countries

United States6 sites, 6 recruiting

  • University of Alabama at Birmingham School of Medicine, Division of Hematology and Oncology

    Birmingham, Alabama, 35233

    Recruiting

  • Columbia University Medical Center

    Fort Lee, New Jersey, 07024

    Recruiting

  • Lake City Cancer Center

    Lake City, Florida, 32024

    Recruiting

  • Memorial Sloan Kettering Cancer Center (MSKCC)

    New York, New York, 10065

    Recruiting

  • Carle Cancer Center

    Urbana, Illinois, 61801

    Recruiting

  • The Oncology Institute of Hope

    Whittier, California, 90603

    Recruiting

Other trials in United States

France6 sites, 6 recruiting

  • Chu Amiens Picardie Site Sud

    Amiens, 80054

    Recruiting

  • CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire

    Limoges, 87042

    Recruiting

  • CHU Nantes - Hôtel Dieu

    Nantes, 44093

    Recruiting

  • CHU de Nice Hospital

    Nice, 06200

    Recruiting

  • Hôpital Saint Louis

    Paris, 75475

    Recruiting

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 63310

    Recruiting

Other trials in France

Italy5 sites, 5 recruiting

  • Polyclinic S. Orsola-Malpighi

    Bologna, 40138

    Recruiting

  • ASST Spedali Civili di Brescia

    Brescia, 25123

    Recruiting

  • Careggi University Hospital

    Florence, 50134

    Recruiting

  • Hospital Casa Sollievo della Sofferenza, Department of Oncology and Hematology, Division of Hematology

    Foggia, 71013

    Recruiting

  • Hospital of Ravenna, Operative Unit of Hematology

    Ravenna, 48121

    Recruiting

Other trials in Italy

Poland5 sites, 5 recruiting

  • Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology

    Bydgoszcz, 85-168

    Recruiting

  • Pratia Onkologia Katowice

    Katowice, 40-519

    Recruiting

  • Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology

    Rzeszów, 35-055

    Recruiting

  • Slupsk Provincial Specialist Hospital n.a. Janusz Korczak, Department of Hematology

    Słupsk, 76-200

    Recruiting

  • Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka

    Torun, 87-100

    Recruiting

Other trials in Poland

Hungary4 sites, 4 recruiting

  • Moritz Kaposi General Hospital, Department of Hematology

    Kaposvár, H-7400

    Recruiting

  • Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology

    Nyíregyháza, H-4400

    Recruiting

  • Medical Center of the University of Pecs, 1st Department of Internal Medicine, Division of Hematology

    Pécs, H-7624

    Recruiting

  • Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine III, Hematology

    Székesfehérvár, H-8000

    Recruiting

Other trials in Hungary

Bulgaria3 sites, 3 recruiting

  • University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven

    Pleven, 5800

    Recruiting

  • University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv

    Plovdiv, 4002

    Recruiting

  • Hematology Clinic Specialized Hospital for Active Treatment of Hematological Diseases, Sofia

    Sofia, 1756

    Recruiting

Other trials in Bulgaria

Austria2 sites, 2 recruiting

  • LKH Hochsteiermark

    Leoben, 8700

    Recruiting

  • Meduni Wien, Univ. Klinik für Innere Medizin I

    Vienna, 1090

    Recruiting

Other trials in Austria

Germany2 sites, 2 recruiting

  • University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology

    Halle, 06120

    Recruiting

  • University Hospital Marburg, Department of Hematology, Oncology and Immunology

    Marburg, 35043

    Recruiting

Other trials in Germany

Serbia2 sites, 2 recruiting

  • Clinical Center of Serbia

    Belgrade, 11000

    Recruiting

  • Clinical Center of Vojvodina

    Novi Sad, 21000

    Recruiting

Other trials in Serbia

Spain2 sites, 2 recruiting

  • Hematologia Clínica

    Barcelona, 08003

    Recruiting

  • University Clinical Hospital of Salamanca, Department of Hematology

    Salamanca, 37007

    Recruiting

Other trials in Spain

About this study

Official title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With TL-895 for the Treatment of Relapsed or Refractory Myelofibrosis and KRT-232 for the Treatment of JAK Inhibitor Intolerant Myelofibrosis.

This study evaluates KRT-232 in Combination With TL-895 for the Treatment of Relapsed or Refractory Myelofibrosis and KRT-232 for the Treatment of JAK Inhibitor Intolerant Myelofibrosis.

Read the detailed description

Cohorts 1 and 2 will undergo dose finding and dose expansion. Eligible patients will be randomly assigned to an open cohort, either Cohort 1 or Cohort 2. Cohort 3 will be conducted as a dose expansion, independent of Cohorts 1 and 2.

Cohort 1 will follow a 3+3 dose escalation design to determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) of TL-895 administered QD in combination with KRT-232. A Safety Review Committee (SRC) will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.

Cohort 2 will follow a 3+3 dose escalation design to determine the MTD/MAD and recommended RP2D of TL-895 administered BID in combination with KRT-232. An SRC will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.

Cohort 3 will be conducted a 2-stage design. In stage 1, enrollment will continue until 15 evaluable patients have been enrolled. An SRC will review the data during the study and if there are ≥4 responders based on the futility criteria and safety data from Stage 1, Cohort 3 expansion will commence. If there are ≤3 patients responding to therapy, Cohort 3 will be terminated. Once expansion criteria have been met, Cohort 3 will be expanded to a total of 46 evaluable patients for Stage 2 analyses.

Being tested
KRT-232, TL-895
Keywords
Relapsed/Refractory Myelofibrosis, Janus associated Kinase Inhibitor-Intolerant Myelofibrosis, MDM2, 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, administered by mouth

  • TL-895Drug

    TL-895, administered by mouth

Study groups in NCT04640532
Study groupRoleWhat they receive
Cohort 1 (R/R MF), Dose Level 1ExperimentalTL-895 at 200 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
Receives: Drug: KRT-232; Drug: TL-895
Cohort 1 (R/R MF), Dose Level 2ExperimentalTL-895 at 300 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
Receives: Drug: KRT-232; Drug: TL-895
Cohort 2 (R/R MF), Dose Level 1ExperimentalTL-895 at 100 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
Receives: Drug: KRT-232; Drug: TL-895
Cohort 2 (R/R MF), Dose Level 2ExperimentalTL-895 at 150 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
Receives: Drug: KRT-232; Drug: TL-895
Cohort 3 (JAKi Intolerant MF)ExperimentalKRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Receives: Drug: KRT-232

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b - The MTD/MAD and RP2D of TL-895 in combination with KRT-232 in patients with R/R MF (Cohort 1 and Cohort 2)

    DLTs will be used to establish the MTD. RP2D will be determined by the SRC based on safety data from the combination of TL-895 and KRT-232.

    Measured: 56 Days

  2. Phase 2 - Spleen response rate for each cohort

    A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 24

    Measured: 24 Weeks

Secondary outcomes (1)

  1. Total Symptom Score (TSS)

    The change in TSS based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)

    Measured: 24 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2020
  2. Study start17 Nov 2020
  3. Primary completion11 May 2022 (estimated)
  4. Study completion24 Jul 2025 (estimated)

Resources

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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
116 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04640532
Sponsor's protocol ID
KRT-232-113
Status last verified
May 2022
First submitted
17 Nov 2020
Last updated
9 May 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing KRT-232 and TL-895 in people with Myelofibrosis and Post-PV MF, run by Kartos Therapeutics, Inc. at 37 sites in 10 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 4 inclusion and 6 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 37 sites in United States, France, Italy, Poland, Hungary and 5 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?

Phase 1b - The MTD/MAD and RP2D of TL-895 in combination with KRT-232 in patients with R/R MF (Cohort 1 and Cohort 2) (time frame: 56 Days). 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?

On the ClinicalTrials.gov record for NCT04640532.

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; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in