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

Phase 2

Recruiting

• Conditions: Primary Myelofibrosis (PMF); Post-Polycythemia Vera Myelofibrosis (Post-PV-MF); Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)
• Interventions: Drug: TL-895; Drug: KRT-232

• Registration Number: NCT04878003
• Lead Sponsor: Kartos Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-13
• Study First Submitted: 2021-05-04
• Study First Submitted QC: 2021-05-04
• Study First Posted: 2021-05-07
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-05
• Last Update Posted: 2022-05-09
• Primary Completion: 2024-05
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 52

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2	TL-895	TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles
Arm 1	KRT-232	KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Spleen Response Duration	48 months	Time from initial SVR of ≥35% by MRI/CT (central review) until progression
Rate of conversion from RBC transfusion dependent to independent	24 weeks	The proportion of subjects who convert from transfusion dependent to transfusion independent at Week 24
Progression free survival (PFS)	48 months	Time from randomization to either first occurrence of disease progression or death due to any cause
Improvement in Total Symptom Score (TSS)	24 weeks	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
Overall Survival (OS)	48 months	Time from first dose to death from any cause

Trial Locations

Locations (28)

Innovative Clinical Research Institute; 🇺🇸 Whittier, California, United States

City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City Council; 🇺🇦 Dnipro, Ukraine

Minsk Scientific and Practice Center of Surgery, Transplantology and Hematology; 🇧🇾 Minsk, Belarus

Republican Hospital n.a. V.A. Baranov; 🇷🇺 Petrozavodsk, Russian Federation

Almazov National Medical Research Centre; 🇷🇺 Saint Petersburg, Russian Federation

Pavlov First Saint Petersburg State Medical University; 🇷🇺 Saint Petersburg, Russian Federation

Botkin City Clinical Hospital; 🇷🇺 Moscow, Russian Federation

Samara State Medical University; 🇷🇺 Samara, Russian Federation

Almazov National Medical Research Center; 🇷🇺 Saint Petersburg, Russian Federation

Wits Baragwanath Clinical Hematology Department; 🇿🇦 Soweto, South Africa

Centro de Investigacion Medica Aquascalientes (CIMA); 🇲🇽 Aguascalientes, Mexico

Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich; 🇵🇱 Katowice, Poland

Szpital Wojewodzki w Opolu Sp. z o.o., Oddzial Hematologii i Onkologii Hematologicznej; 🇵🇱 Opole, Poland

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.; 🇵🇱 Słupsk, Poland

Military Medical Academy; 🇧🇬 Sofia, Bulgaria

Sociedad de Metabolismo Y Corazon - SOMECO; 🇲🇽 Veracruz, Mexico

UMHAT Sv. Ivan Rilski EAD; 🇧🇬 Sofia, Bulgaria

JSC EVEX Hospitals; 🇬🇪 Kutaisi, Georgia

LTD M.Zodelava Hematology Centre; 🇬🇪 Tbilisi, Georgia

UMHAT Georgi Stranski; 🇧🇬 Pleven, Bulgaria

Medical Centre Hipokrat N; 🇧🇬 Plovdiv, Bulgaria

Specialized Hospital for Active Treatment of Hematologic Diseases; 🇧🇬 Sofia, Bulgaria

Unidad de Investigacion CIMA SC; 🇲🇽 Chihuahua, Mexico

K.Eristavi National Center of Experimental and Clinical Surgery; 🇬🇪 Tbilisi, Georgia

Republican Scientific Practical Center of Radiation Medicine and Human Ecology; 🇧🇾 Belarus, Belarus

Gabrail Cancer Center; 🇺🇸 Canton, Ohio, United States

Centro de Investigacion Clinica de Oaxaca (CICLO); 🇲🇽 Oaxaca, Mexico

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States