KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera
- Registration Number
- NCT03669965
- Lead Sponsor
- Kartos Therapeutics, Inc.
- Brief Summary
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with phlebotomy-dependent polycythemia vera (PV). Inhibition of MDM2 in PV is a new mechanism of action in PV. In Part A, patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon. In Part B, patients must be resistant or intolerant to hydroxyurea.
This study is a global, open-label Phase 2a/2b study to determine the efficacy and safety of KRT-232. In Part A of the study, patients will be randomly assigned to 5 arms with 2 different doses and 3 different dosing schedules of KRT 232. In Part B of the study, patients will be randomized either to treatment with KRT-232 administered at the recommended dose and schedule from Part A or to treatment with ruxolitinib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 20
- Confirmed diagnosis of PV (WHO 2016)
- ECOG ≤ 2
- Part A: patients with and without splenomegaly are eligible
- Part A: patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon
- Part B: only patients with splenomegaly are eligible
- Part B: patients must be resistant or intolerant to hydroxyurea
- Diagnosis of post-PV myelofibrosis (IWG-MRT)
- Prior treatment with MDM2 inhibitors, p53-directed therapies, HDAC, BCL 2 inhibitors
- Splenic irradiation within 3 months prior to the first dose of study treatment
- Clinically significant thrombosis within 3 months of screening
- Grade 2 or higher QTc prolongation
- Part B: prior treatment with a JAK inhibitor
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A Arm 2 KRT-232 KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) Part A Arm 4b KRT-232 KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles) Part A Arm 2b KRT-232 KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) Part B KRT-232 Arm KRT-232 Recommended KRT-232 dose and schedule from Part A Part A Arm 3 KRT-232 KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles) Part A Arm 1 KRT-232 KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles) Part B Ruxolitinib Arm Ruxolitinib Ruxolitinib per approved prescribing label
- Primary Outcome Measures
Name Time Method Proportion of patients with splenomegaly achieving a response at Week 32 32 weeks Response defined as having achieved both of the following:
* The absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32, with no more than one phlebotomy eligibility occurring post-randomization and prior to the Week 8 visit
* A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 32
- Secondary Outcome Measures
Name Time Method Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly) 4 years Duration of response after achieving phlebotomy independence 4 years Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome 32 weeks Change from baseline of EORTC-QLQ-C30 patient-reported outcome 32 weeks
Trial Locations
- Locations (16)
Békés Megyei Központi Kórház Pándy Kálmán Tagkórház
🇭🇺Gyula, Hungary
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Stauferklinikum Schwäbisch Gmünd
🇩🇪Mutlangen, Germany
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Southern California Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
The Kirklin Clinic of UAB Hospital
🇺🇸Birmingham, Alabama, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hospital Universitario de Gran Canaria Doctor Negrin
🇪🇸Las Palmas de Gran Canaria, LAS Palmas, Spain
Szpital Wojewódzki w Opolu
🇵🇱Opole, Poland
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
🇩🇪Dresden, Sachsen, Germany
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
🇵🇱Wrocław, Dolnoslaskie, Poland
Center Hospitalier Universitaire d'Angers
🇫🇷Angers, France
Universitätsklinikum Aachen
🇩🇪Aachen, Nordrhein-westfalen, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States