KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera

Phase 2Active Not RecruitingNCT03669965

Kartos Therapeutics, Inc.20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Polycythemia Vera

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (16)

The Kirklin Clinic of UAB Hospital

Birmingham, Alabama, United States

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, United States

Washington University School of Medicine

St Louis, Missouri, United States

Gabrail Cancer Center

Canton, Ohio, United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Center Hospitalier Universitaire d'Angers

Angers, France

Universitätsklinikum Aachen

Aachen, North Rhine-Westphalia, Germany

Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle

Dresden, Saxony, Germany

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

Stauferklinikum Schwäbisch Gmünd

Mutlangen, Germany

...and 6 more locations

Outcomes

Primary Outcomes

Proportion of patients with splenomegaly achieving a response at Week 32

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

Time frame: 32 weeks

Secondary Outcomes

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