UAB - Center for Clinical and Translational Science

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

Purpose

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

Polycythemia Vera

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: 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

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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)	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)	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)	Drug: KRT-232 KRT-232, administered by mouth
Experimental Part B KRT-232 Arm	Recommended KRT-232 dose and schedule from Part A	Drug: KRT-232 KRT-232, administered by mouth
Active Comparator Part B Ruxolitinib Arm	Ruxolitinib per approved prescribing label	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)	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)	Drug: KRT-232 KRT-232, administered by mouth

More Details

Status: Unknown status
Sponsor: Kartos Therapeutics, Inc.

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.