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

NCT03669965 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: KRT-232-102
• Study Type: interventional
• Target: 20
• Locations: 6 countries
• Sites: 16

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.

Conditions

Polycythemia Vera

Outcome Measures

Primary Outcomes (1)

• 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

  32 weeks

Secondary Outcomes (4)

• 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

Other Outcomes (1)

• 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

  28 weeks

Study Arms (7)

Part A Arm 1

EXPERIMENTAL

KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

Drug: KRT-232

Part A Arm 2

EXPERIMENTAL

KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

Drug: KRT-232

Part A Arm 3

EXPERIMENTAL

KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Drug: KRT-232

Part B KRT-232 Arm

EXPERIMENTAL

Recommended KRT-232 dose and schedule from Part A

Drug: KRT-232

Part B Ruxolitinib Arm

ACTIVE COMPARATOR

Ruxolitinib per approved prescribing label

Drug: Ruxolitinib

Part A Arm 4b

EXPERIMENTAL

KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)

Drug: KRT-232

Part A Arm 2b

EXPERIMENTAL

KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Drug: KRT-232

Interventions

KRT-232 DRUG

KRT-232, administered by mouth

Part A Arm 1; Part A Arm 2; Part A Arm 2b; Part A Arm 3; Part A Arm 4b; Part B KRT-232 Arm

Ruxolitinib DRUG

Ruxolitinib per approved prescribing label

Part B Ruxolitinib Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kartos Therapeutics, Inc.: lead

Study Sites (16)

The Kirklin Clinic of UAB Hospital

Birmingham, Alabama, 35249, United States

Location

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Center Hospitalier Universitaire d'Angers

Angers, 49933 Cedex 09, France

Location

Universitätsklinikum Aachen

Aachen, North Rhine-Westphalia, Germany

Location

Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle

Dresden, Saxony, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

Location

Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Békés Megyei Központi Kórház Pándy Kálmán Tagkórház

Gyula, 5700, Hungary

Location

Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku

Wroclaw, Lower Silesian Voivodeship, Poland

Location

Szpital Wojewódzki w Opolu

Opole, 45-061, Poland

Location

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, LAS Palmas, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

MeSH Terms

Conditions

Polycythemia Vera

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid; ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2018
• First Posted: September 13, 2018
• Study Start: January 15, 2019
• Primary Completion: April 1, 2022
• Study Completion: October 1, 2022
• Last Updated: July 31, 2020

Record last verified: 2020-07

Locations

DE (4); US (5); FR (1); HU (1); PL (2); ES (3)