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

Sponsor

Kartos Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04878003

Collaborator

(none)

Enrollment

Locations

Arms

53.6

Anticipated Duration (Months)

1.8

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis (PMF) Post-Polycythemia Vera Myelofibrosis (Post-PV-MF) Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)	Drug: KRT-232 Drug: TL-895	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 13, 2021

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 KRT-232 administered orally as 240 mg once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles	Drug: KRT-232 KRT-232, administration by mouth
Experimental: Arm 2 TL-895 administered orally as 150 mg twice daily continuously in 28-day cycles	Drug: TL-895 TL-895, administration by mouth

Arm

Intervention/Treatment

Experimental: Arm 1

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

Drug: KRT-232

KRT-232, administration by mouth

Experimental: Arm 2

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

Drug: TL-895

TL-895, administration by mouth

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
Overall Survival (OS) [48 months]
Time from first dose to death from any cause
Progression free survival (PFS) [48 months]
Time from randomization to either first occurrence of disease progression or death due to any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Innovative Clinical Research Institute	Glendale	California	United States	90603
2	Innovative Clinical Research Institute	Whittier	California	United States	90603
3	Gabrail Cancer Center	Canton	Ohio	United States	44718
4	MD Anderson Cancer Center	Houston	Texas	United States	77030
5	Republican Scientific Practical Center of Radiation Medicine and Human Ecology	Belarus		Belarus	246040
6	Minsk Scientific and Practice Center of Surgery, Transplantology and Hematology	Minsk		Belarus	220045
7	UMHAT Georgi Stranski	Pleven		Bulgaria	5800
8	Medical Centre Hipokrat N	Plovdiv		Bulgaria	4000
9	UMHAT Sv. Ivan Rilski EAD	Sofia		Bulgaria	1431
10	Military Medical Academy	Sofia		Bulgaria	1606
11	Specialized Hospital for Active Treatment of Hematologic Diseases	Sofia		Bulgaria	1756
12	JSC EVEX Hospitals	Kutaisi		Georgia	4600
13	LTD M.Zodelava Hematology Centre	Tbilisi		Georgia	112
14	K.Eristavi National Center of Experimental and Clinical Surgery	Tbilisi		Georgia	159
15	Centro de Investigacion Medica Aquascalientes (CIMA)	Aguascalientes		Mexico	20116
16	Unidad de Investigacion CIMA SC	Chihuahua		Mexico	31200
17	Centro de Investigacion Clinica de Oaxaca (CICLO)	Oaxaca		Mexico	68020
18	Sociedad de Metabolismo Y Corazon - SOMECO	Veracruz		Mexico	91900
19	Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich	Katowice		Poland	40-519
20	Szpital Wojewodzki w Opolu Sp. z o.o., Oddzial Hematologii i Onkologii Hematologicznej	Opole		Poland	45-061
21	Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.	Słupsk		Poland	76-200
22	Botkin City Clinical Hospital	Moscow		Russian Federation	125284
23	Republican Hospital n.a. V.A. Baranov	Petrozavodsk		Russian Federation	185019
24	Pavlov First Saint Petersburg State Medical University	Saint Petersburg		Russian Federation	197022
25	Almazov National Medical Research Center	Saint Petersburg		Russian Federation	197341
26	Almazov National Medical Research Centre	Saint Petersburg		Russian Federation	197341
27	Samara State Medical University	Samara		Russian Federation	443099
28	Wits Baragwanath Clinical Hematology Department	Soweto		South Africa	1519
29	City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City Council	Dnipro		Ukraine	49102