Clinical trial NCT03669965: KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Polycythemia Vera
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-13
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with splenomegaly achieving a response at Week 32
timeFrame: 32 weeks
Secondary outcomes:
measure: Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly)
timeFrame: 4 years
measure: Duration of response after achieving phlebotomy independence
timeFrame: 4 years
measure: Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome
timeFrame: 32 weeks
measure: Change from baseline of EORTC-QLQ-C30 patient-reported outcome
timeFrame: 32 weeks
Other outcomes:
measure: 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
timeFrame: 28 weeks
Locations:
city: Birmingham
country: United States
facility: The Kirklin Clinic of UAB Hospital
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer Center
state: California
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Angers
country: France
facility: Center Hospitalier Universitaire d'Angers
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
state: Nordrhein-westfalen
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
state: Sachsen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch Gmünd
city: Gyula
country: Hungary
facility: Békés Megyei Központi Kórház Pándy Kálmán Tagkórház
city: Wrocław
country: Poland
facility: Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
state: Dolnoslaskie
city: Opole
country: Poland
facility: Szpital Wojewódzki w Opolu
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrin
state: LAS Palmas
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
Study officials:
References: