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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 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.

Exclusion Criteria:

  • - 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04640532
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Kartos Therapeutics, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Austria, Bulgaria, France, Germany, Hungary, Italy, Poland, Serbia, Spain, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis
Additional Details

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.

Arms & Interventions

Arms

Experimental: Cohort 1 (R/R MF), Dose Level 1

TL-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.

Experimental: Cohort 1 (R/R MF), Dose Level 2

TL-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.

Experimental: Cohort 2 (R/R MF), Dose Level 1

TL-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.

Experimental: Cohort 2 (R/R MF), Dose Level 2

TL-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.

Experimental: Cohort 3 (JAKi Intolerant MF)

KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.

Interventions

Drug: - KRT-232

KRT-232, administered by mouth

Drug: - TL-895

TL-895, administered by mouth

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Birmingham, Alabama

Status

Recruiting

Address

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

Birmingham, Alabama, 35233

The Oncology Institute of Hope, Whittier, California

Status

Recruiting

Address

The Oncology Institute of Hope

Whittier, California, 90603

Lake City Cancer Center, Lake City, Florida

Status

Recruiting

Address

Lake City Cancer Center

Lake City, Florida, 32024

Carle Cancer Center, Urbana, Illinois

Status

Recruiting

Address

Carle Cancer Center

Urbana, Illinois, 61801

Columbia University Medical Center, Fort Lee, New Jersey

Status

Recruiting

Address

Columbia University Medical Center

Fort Lee, New Jersey, 07024

New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10065

International Sites

LKH Hochsteiermark, Leoben, Austria

Status

Recruiting

Address

LKH Hochsteiermark

Leoben, , 8700

Wien, Austria

Status

Recruiting

Address

Meduni Wien, Univ. Klinik für Innere Medizin I

Wien, , 1090

Pleven, Bulgaria

Status

Recruiting

Address

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

Pleven, , 5800

Plovdiv, Bulgaria

Status

Recruiting

Address

University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv

Plovdiv, , 4002

Sofia, Bulgaria

Status

Recruiting

Address

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

Sofia, , 1756

Chu Amiens Picardie Site Sud, Amiens, France

Status

Recruiting

Address

Chu Amiens Picardie Site Sud

Amiens, , 80054

Limoges, France

Status

Recruiting

Address

CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire

Limoges, , 87042

CHU Nantes - Hôtel Dieu, Nantes, France

Status

Recruiting

Address

CHU Nantes - Hôtel Dieu

Nantes, , 44093

CHU de Nice Hospital, Nice, France

Status

Recruiting

Address

CHU de Nice Hospital

Nice, , 06200

Hôpital Saint Louis, Paris, France

Status

Recruiting

Address

Hôpital Saint Louis

Paris, , 75475

Centre Hospitalier Lyon Sud, Pierre-Bénite, France

Status

Recruiting

Address

Centre Hospitalier Lyon Sud

Pierre-Bénite, , 63310

Halle, Germany

Status

Recruiting

Address

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

Halle, , 06120

Marburg, Germany

Status

Recruiting

Address

University Hospital Marburg, Department of Hematology, Oncology and Immunology

Marburg, , 35043

Kaposvár, Hungary

Status

Recruiting

Address

Moritz Kaposi General Hospital, Department of Hematology

Kaposvár, , H-7400

Nyíregyháza, Hungary

Status

Recruiting

Address

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

Nyíregyháza, , H-4400

Pécs, Hungary

Status

Recruiting

Address

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

Pécs, , H-7624

Székesfehérvár, Hungary

Status

Recruiting

Address

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

Székesfehérvár, , H-8000

Polyclinic S. Orsola-Malpighi, Bologna, Italy

Status

Recruiting

Address

Polyclinic S. Orsola-Malpighi

Bologna, , 40138

ASST Spedali Civili di Brescia, Brescia, Italy

Status

Recruiting

Address

ASST Spedali Civili di Brescia

Brescia, , 25123

Careggi University Hospital, Florence, Italy

Status

Recruiting

Address

Careggi University Hospital

Florence, , 50134

Foggia, Italy

Status

Recruiting

Address

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

Foggia, , 71013

Ravenna, Italy

Status

Recruiting

Address

Hospital of Ravenna, Operative Unit of Hematology

Ravenna, , 48121

Bydgoszcz, Poland

Status

Recruiting

Address

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

Bydgoszcz, , 85-168

Pratia Onkologia Katowice, Katowice, Poland

Status

Recruiting

Address

Pratia Onkologia Katowice

Katowice, , 40-519

Rzeszów, Poland

Status

Recruiting

Address

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

Rzeszów, , 35-055

Słupsk, Poland

Status

Recruiting

Address

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

Słupsk, , 76-200

Toruń, Poland

Status

Recruiting

Address

Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka

Toruń, , 87-100

Clinical Center of Serbia, Belgrade, Serbia

Status

Recruiting

Address

Clinical Center of Serbia

Belgrade, , 11000

Clinical Center of Vojvodina, Novi Sad, Serbia

Status

Recruiting

Address

Clinical Center of Vojvodina

Novi Sad, , 21000

Hematologia Clínica, Barcelona, Spain

Status

Recruiting

Address

Hematologia Clínica

Barcelona, , 08003

Salamanca, Spain

Status

Recruiting

Address

University Clinical Hospital of Salamanca, Department of Hematology

Salamanca, , 37007