Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
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 |
---|---|---|
Phase 2 |
Study Design
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
|
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
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 |
Sponsors and Collaborators
- Kartos Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KRT-232-114