NCT04640532

Brief 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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
116

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2020

Longer than P75 for phase_1

Geographic Reach
10 countries

37 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 17, 2020

Completed
Same day until next milestone

Study Start

First participant enrolled

November 17, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

November 23, 2020

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 11, 2022

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 24, 2025

Completed
Last Updated

May 9, 2022

Status Verified

May 1, 2022

Enrollment Period

1.5 years

First QC Date

November 17, 2020

Last Update Submit

May 5, 2022

Conditions

MyelofibrosisPost-PV MFPost-ET MyelofibrosisPrimary Myelofibrosis

Keywords

Relapsed/Refractory MyelofibrosisJanus associated Kinase Inhibitor-Intolerant MyelofibrosisMDM2navtemadlin

Outcome Measures

Primary Outcomes (2)

  • 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.

    56 Days

  • 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

    24 Weeks

Secondary Outcomes (1)

  • Total Symptom Score (TSS)

    24 Weeks

Study Arms (5)

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

EXPERIMENTAL

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.

Drug: KRT-232Drug: TL-895

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

EXPERIMENTAL

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.

Drug: KRT-232Drug: TL-895

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

EXPERIMENTAL

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.

Drug: KRT-232Drug: TL-895

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

EXPERIMENTAL

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.

Drug: KRT-232Drug: TL-895

Cohort 3 (JAKi Intolerant MF)

EXPERIMENTAL

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

Drug: KRT-232

Interventions

KRT-232DRUG

KRT-232, administered by mouth

Cohort 1 (R/R MF), Dose Level 1Cohort 1 (R/R MF), Dose Level 2Cohort 2 (R/R MF), Dose Level 1Cohort 2 (R/R MF), Dose Level 2Cohort 3 (JAKi Intolerant MF)
TL-895DRUG

TL-895, administered by mouth

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

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (37)

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

Birmingham, Alabama, 35233, United States

RECRUITING

The Oncology Institute of Hope

Whittier, California, 90603, United States

RECRUITING

Lake City Cancer Center

Lake City, Florida, 32024, United States

RECRUITING

Carle Cancer Center

Urbana, Illinois, 61801, United States

RECRUITING

Columbia University Medical Center

Fort Lee, New Jersey, 07024, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10065, United States

RECRUITING

LKH Hochsteiermark

Leoben, 8700, Austria

RECRUITING

Meduni Wien, Univ. Klinik für Innere Medizin I

Vienna, 1090, Austria

RECRUITING

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

Pleven, 5800, Bulgaria

RECRUITING

University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv

Plovdiv, 4002, Bulgaria

RECRUITING

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

Sofia, 1756, Bulgaria

RECRUITING

Chu Amiens Picardie Site Sud

Amiens, 80054, France

RECRUITING

CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire

Limoges, 87042, France

RECRUITING

CHU Nantes - Hôtel Dieu

Nantes, 44093, France

RECRUITING

CHU de Nice Hospital

Nice, 06200, France

RECRUITING

Hôpital Saint Louis

Paris, 75475, France

RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, 63310, France

RECRUITING

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

Halle, 06120, Germany

RECRUITING

University Hospital Marburg, Department of Hematology, Oncology and Immunology

Marburg, 35043, Germany

RECRUITING

Moritz Kaposi General Hospital, Department of Hematology

Kaposvár, H-7400, Hungary

RECRUITING

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

Nyíregyháza, H-4400, Hungary

RECRUITING

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

Pécs, H-7624, Hungary

RECRUITING

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

Székesfehérvár, H-8000, Hungary

RECRUITING

Polyclinic S. Orsola-Malpighi

Bologna, 40138, Italy

RECRUITING

ASST Spedali Civili di Brescia

Brescia, 25123, Italy

RECRUITING

Careggi University Hospital

Florence, 50134, Italy

RECRUITING

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

Foggia, 71013, Italy

RECRUITING

Hospital of Ravenna, Operative Unit of Hematology

Ravenna, 48121, Italy

RECRUITING

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

Bydgoszcz, 85-168, Poland

RECRUITING

Pratia Onkologia Katowice

Katowice, 40-519, Poland

RECRUITING

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

Rzeszów, 35-055, Poland

RECRUITING

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

Słupsk, 76-200, Poland

RECRUITING

Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka

Torun, 87-100, Poland

RECRUITING

Clinical Center of Serbia

Belgrade, 11000, Serbia

RECRUITING

Clinical Center of Vojvodina

Novi Sad, 21000, Serbia

RECRUITING

Hematologia Clínica

Barcelona, 08003, Spain

RECRUITING

University Clinical Hospital of Salamanca, Department of Hematology

Salamanca, 37007, Spain

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Condition Hierarchy (Ancestors)

Myeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Central Study Contacts

John Mei

CONTACT

650-542-0136jmei@kartosthera.com

Irene Dea

CONTACT

(650) 839-7341idea@kartosthera.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 17, 2020

First Posted

November 23, 2020

Study Start

November 17, 2020

Primary Completion

May 11, 2022

Study Completion

July 24, 2025

Last Updated

May 9, 2022

Record last verified: 2022-05

Locations

DE(2)HU(4)BU(3)US(6)FR(6)IT(5)AU(2)PL(5)SE(2)ES(2)