KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera
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ClinicalTrials.gov Identifier: NCT03669965 |
Recruitment Status :
Active, not recruiting
First Posted : September 13, 2018
Last Update Posted : July 31, 2020
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Polycythemia Vera | Drug: KRT-232 Drug: Ruxolitinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 20 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Two-Part, Randomized, Open-label, Multicenter, Phase 2a/2b Study of the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera |
Actual Study Start Date : | January 15, 2019 |
Estimated Primary Completion Date : | April 2022 |
Estimated Study Completion Date : | October 2022 |

Arm | Intervention/treatment |
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Experimental: Part A Arm 1
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
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Drug: KRT-232
KRT-232, administered by mouth |
Experimental: Part A Arm 2
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
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Drug: KRT-232
KRT-232, administered by mouth |
Experimental: Part A Arm 3
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
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Drug: KRT-232
KRT-232, administered by mouth |
Experimental: Part B KRT-232 Arm
Recommended KRT-232 dose and schedule from Part A
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Drug: KRT-232
KRT-232, administered by mouth |
Active Comparator: Part B Ruxolitinib Arm
Ruxolitinib per approved prescribing label
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Drug: Ruxolitinib
Ruxolitinib per approved prescribing label |
Experimental: Part A Arm 4b
KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
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Drug: KRT-232
KRT-232, administered by mouth |
Experimental: Part A Arm 2b
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
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Drug: KRT-232
KRT-232, administered by mouth |
- Proportion of patients with splenomegaly achieving a response at Week 32 [ Time Frame: 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
- Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly) [ Time Frame: 4 years ]
- Duration of response after achieving phlebotomy independence [ Time Frame: 4 years ]
- Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome [ Time Frame: 32 weeks ]
- Change from baseline of EORTC-QLQ-C30 patient-reported outcome [ Time Frame: 32 weeks ]
- Proportion of patients without splenomegaly achieving the absence of phlebotomy eligibility beginning at the Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post-randomization and prior to Week 8 [ Time Frame: 28 weeks ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03669965
United States, Alabama | |
The Kirklin Clinic of UAB Hospital | |
Birmingham, Alabama, United States, 35249 | |
United States, California | |
University of Southern California Norris Comprehensive Cancer Center | |
Los Angeles, California, United States, 90033 | |
United States, Missouri | |
Washington University School of Medicine | |
Saint Louis, Missouri, United States, 63110 | |
United States, Ohio | |
Gabrail Cancer Center | |
Canton, Ohio, United States, 44718 | |
The Ohio State University Comprehensive Cancer Center | |
Columbus, Ohio, United States, 43210 | |
France | |
Center Hospitalier Universitaire d'Angers | |
Angers, France, 49933 Cedex 09 | |
Germany | |
Universitätsklinikum Aachen | |
Aachen, Nordrhein-westfalen, Germany | |
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle | |
Dresden, Sachsen, Germany | |
Universitätsklinikum Carl Gustav Carus | |
Dresden, Sachsen, Germany | |
Stauferklinikum Schwäbisch Gmünd | |
Mutlangen, Germany, 73557 | |
Hungary | |
Békés Megyei Központi Kórház Pándy Kálmán Tagkórház | |
Gyula, Hungary, 5700 | |
Poland | |
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku | |
Wrocław, Dolnoslaskie, Poland | |
Szpital Wojewódzki w Opolu | |
Opole, Poland, 45-061 | |
Spain | |
Hospital Universitario de Gran Canaria Doctor Negrin | |
Las Palmas de Gran Canaria, LAS Palmas, Spain | |
Hospital Universitario Virgen de la Victoria | |
Málaga, Spain, 29010 | |
Hospital Universitario de Salamanca | |
Salamanca, Spain, 37007 |
Responsible Party: | Kartos Therapeutics, Inc. |
ClinicalTrials.gov Identifier: | NCT03669965 |
Other Study ID Numbers: |
KRT-232-102 |
First Posted: | September 13, 2018 Key Record Dates |
Last Update Posted: | July 31, 2020 |
Last Verified: | July 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Polycythemia Vera Polycythemia Hematologic Diseases Bone Marrow Neoplasms Hematologic Neoplasms |
Neoplasms by Site Neoplasms Bone Marrow Diseases Myeloproliferative Disorders |