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

Primary Myelofibrosis (PMF) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04878003
• Other study ID #: KRT-232-114
• Status: Recruiting
• Phase: Phase 2
• Start date: April 13, 2021
• Est. completion date: October 2025

Study information

• Verified date: May 2022
• Source: Kartos Therapeutics, Inc.
• Contact: John Mei
• Phone: 650-542-0136
• Email: jmei[@]kartosthera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: October 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera
• Primary Myelofibrosis
• Primary Myelofibrosis (PMF)
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• KRT-232
KRT-232, administration by mouth
• TL-895
TL-895, administration by mouth

Locations

Country	Name	City	State
Belarus	Republican Scientific Practical Center of Radiation Medicine and Human Ecology	Belarus
Belarus	Minsk Scientific and Practice Center of Surgery, Transplantology and Hematology	Minsk
Bulgaria	UMHAT Georgi Stranski	Pleven
Bulgaria	Medical Centre Hipokrat N	Plovdiv
Bulgaria	Military Medical Academy	Sofia
Bulgaria	Specialized Hospital for Active Treatment of Hematologic Diseases	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski EAD	Sofia
Georgia	JSC EVEX Hospitals	Kutaisi
Georgia	K.Eristavi National Center of Experimental and Clinical Surgery	Tbilisi
Georgia	LTD M.Zodelava Hematology Centre	Tbilisi
Mexico	Centro de Investigacion Medica Aquascalientes (CIMA)	Aguascalientes
Mexico	Unidad de Investigacion CIMA SC	Chihuahua
Mexico	Centro de Investigacion Clinica de Oaxaca (CICLO)	Oaxaca
Mexico	Sociedad de Metabolismo Y Corazon - SOMECO	Veracruz
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespól 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.	Slupsk
Russian Federation	Botkin City Clinical Hospital	Moscow
Russian Federation	Republican Hospital n.a. V.A. Baranov	Petrozavodsk
Russian Federation	Almazov National Medical Research Center	Saint Petersburg
Russian Federation	Almazov National Medical Research Centre	Saint Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	Samara State Medical University	Samara
South Africa	Wits Baragwanath Clinical Hematology Department	Soweto
Ukraine	City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City Council	Dnipro
United States	Gabrail Cancer Center	Canton	Ohio
United States	Innovative Clinical Research Institute	Glendale	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Belarus,  Bulgaria,  Georgia,  Mexico,  Poland,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spleen Volume Reduction (SVR)	The proportion of subjects achieving =35% SVR at Week 24 by MRI/CT (central review)	24 weeks
Secondary	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	24 weeks
Secondary	Spleen Response Duration	Time from initial SVR of =35% by MRI/CT (central review) until progression	48 months
Secondary	Rate of conversion from RBC transfusion dependent to independent	The proportion of subjects who convert from transfusion dependent to transfusion independent at Week 24	24 weeks
Secondary	Overall Survival (OS)	Time from first dose to death from any cause	48 months
Secondary	Progression free survival (PFS)	Time from randomization to either first occurrence of disease progression or death due to any cause	48 months