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Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis

Primary Purpose

Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KRT-232
TL-895
Sponsored by
Kartos Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Myelofibrosis (PMF) focused on measuring navtemadlin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • History of major organ transplant
  • Grade 2 or higher QTc prolongation
  • Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization

Sites / Locations

  • Innovative Clinical Research InstituteRecruiting
  • Innovative Clinical Research InstituteRecruiting
  • Gabrail Cancer CenterRecruiting
  • MD Anderson Cancer CenterRecruiting
  • Republican Scientific Practical Center of Radiation Medicine and Human EcologyRecruiting
  • Minsk Scientific and Practice Center of Surgery, Transplantology and HematologyRecruiting
  • UMHAT Georgi StranskiRecruiting
  • Medical Centre Hipokrat NRecruiting
  • UMHAT Sv. Ivan Rilski EADRecruiting
  • Military Medical AcademyRecruiting
  • Specialized Hospital for Active Treatment of Hematologic DiseasesRecruiting
  • JSC EVEX HospitalsRecruiting
  • LTD M.Zodelava Hematology CentreRecruiting
  • K.Eristavi National Center of Experimental and Clinical SurgeryRecruiting
  • Centro de Investigacion Medica Aquascalientes (CIMA)Recruiting
  • Unidad de Investigacion CIMA SCRecruiting
  • Centro de Investigacion Clinica de Oaxaca (CICLO)Recruiting
  • Sociedad de Metabolismo Y Corazon - SOMECORecruiting
  • Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali MiejskichRecruiting
  • Szpital Wojewodzki w Opolu Sp. z o.o., Oddzial Hematologii i Onkologii HematologicznejRecruiting
  • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.Recruiting
  • Botkin City Clinical HospitalRecruiting
  • Republican Hospital n.a. V.A. BaranovRecruiting
  • Pavlov First Saint Petersburg State Medical UniversityRecruiting
  • Almazov National Medical Research CenterRecruiting
  • Almazov National Medical Research CentreRecruiting
  • Samara State Medical UniversityRecruiting
  • Wits Baragwanath Clinical Hematology DepartmentRecruiting
  • City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City CouncilRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles

TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles

Outcomes

Primary Outcome Measures

Spleen Volume Reduction (SVR)
The proportion of subjects achieving ≥35% SVR at Week 24 by MRI/CT (central review)

Secondary Outcome Measures

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
Spleen Response Duration
Time from initial SVR of ≥35% by MRI/CT (central review) until progression
Rate of conversion from RBC transfusion dependent to independent
The proportion of subjects who convert from transfusion dependent to transfusion independent at Week 24
Overall Survival (OS)
Time from first dose to death from any cause
Progression free survival (PFS)
Time from randomization to either first occurrence of disease progression or death due to any cause

Full Information

First Posted
May 4, 2021
Last Updated
May 5, 2022
Sponsor
Kartos Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04878003
Brief Title
Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 13, 2021 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kartos Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV-MF), Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)
Keywords
navtemadlin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles
Intervention Type
Drug
Intervention Name(s)
KRT-232
Intervention Description
KRT-232, administration by mouth
Intervention Type
Drug
Intervention Name(s)
TL-895
Intervention Description
TL-895, administration by mouth
Primary Outcome Measure Information:
Title
Spleen Volume Reduction (SVR)
Description
The proportion of subjects achieving ≥35% SVR at Week 24 by MRI/CT (central review)
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Improvement in Total Symptom Score (TSS)
Description
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
Time Frame
24 weeks
Title
Spleen Response Duration
Description
Time from initial SVR of ≥35% by MRI/CT (central review) until progression
Time Frame
48 months
Title
Rate of conversion from RBC transfusion dependent to independent
Description
The proportion of subjects who convert from transfusion dependent to transfusion independent at Week 24
Time Frame
24 weeks
Title
Overall Survival (OS)
Description
Time from first dose to death from any cause
Time Frame
48 months
Title
Progression free survival (PFS)
Description
Time from randomization to either first occurrence of disease progression or death due to any cause
Time Frame
48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 History of major organ transplant Grade 2 or higher QTc prolongation Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Mei
Phone
650-542-0136
Email
jmei@kartosthera.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jordan Blevins
Phone
650-542-0136
Email
jblevins@kartosthera.com
Facility Information:
Facility Name
Innovative Clinical Research Institute
City
Glendale
State/Province
California
ZIP/Postal Code
90603
Country
United States
Individual Site Status
Recruiting
Facility Name
Innovative Clinical Research Institute
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Individual Site Status
Recruiting
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Republican Scientific Practical Center of Radiation Medicine and Human Ecology
City
Belarus
ZIP/Postal Code
246040
Country
Belarus
Individual Site Status
Recruiting
Facility Name
Minsk Scientific and Practice Center of Surgery, Transplantology and Hematology
City
Minsk
ZIP/Postal Code
220045
Country
Belarus
Individual Site Status
Recruiting
Facility Name
UMHAT Georgi Stranski
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Medical Centre Hipokrat N
City
Plovdiv
ZIP/Postal Code
4000
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
UMHAT Sv. Ivan Rilski EAD
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Military Medical Academy
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
Specialized Hospital for Active Treatment of Hematologic Diseases
City
Sofia
ZIP/Postal Code
1756
Country
Bulgaria
Individual Site Status
Recruiting
Facility Name
JSC EVEX Hospitals
City
Kutaisi
ZIP/Postal Code
4600
Country
Georgia
Individual Site Status
Recruiting
Facility Name
LTD M.Zodelava Hematology Centre
City
Tbilisi
ZIP/Postal Code
112
Country
Georgia
Individual Site Status
Recruiting
Facility Name
K.Eristavi National Center of Experimental and Clinical Surgery
City
Tbilisi
ZIP/Postal Code
159
Country
Georgia
Individual Site Status
Recruiting
Facility Name
Centro de Investigacion Medica Aquascalientes (CIMA)
City
Aguascalientes
ZIP/Postal Code
20116
Country
Mexico
Individual Site Status
Recruiting
Facility Name
Unidad de Investigacion CIMA SC
City
Chihuahua
ZIP/Postal Code
31200
Country
Mexico
Individual Site Status
Recruiting
Facility Name
Centro de Investigacion Clinica de Oaxaca (CICLO)
City
Oaxaca
ZIP/Postal Code
68020
Country
Mexico
Individual Site Status
Recruiting
Facility Name
Sociedad de Metabolismo Y Corazon - SOMECO
City
Veracruz
ZIP/Postal Code
91900
Country
Mexico
Individual Site Status
Recruiting
Facility Name
Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
City
Katowice
ZIP/Postal Code
40-519
Country
Poland
Individual Site Status
Recruiting
Facility Name
Szpital Wojewodzki w Opolu Sp. z o.o., Oddzial Hematologii i Onkologii Hematologicznej
City
Opole
ZIP/Postal Code
45-061
Country
Poland
Individual Site Status
Recruiting
Facility Name
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
City
Słupsk
ZIP/Postal Code
76-200
Country
Poland
Individual Site Status
Recruiting
Facility Name
Botkin City Clinical Hospital
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Republican Hospital n.a. V.A. Baranov
City
Petrozavodsk
ZIP/Postal Code
185019
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Pavlov First Saint Petersburg State Medical University
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Almazov National Medical Research Center
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Almazov National Medical Research Centre
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Samara State Medical University
City
Samara
ZIP/Postal Code
443099
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Wits Baragwanath Clinical Hematology Department
City
Soweto
ZIP/Postal Code
1519
Country
South Africa
Individual Site Status
Recruiting
Facility Name
City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City Council
City
Dnipro
ZIP/Postal Code
49102
Country
Ukraine
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis

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