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

Sponsor
Kartos Therapeutics, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03669965
Collaborator
(none)
20
Enrollment
16
Locations
7
Arms
44.5
Anticipated Duration (Months)
1.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
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 :
Jan 15, 2019
Anticipated Primary Completion Date :
Apr 1, 2022
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. Proportion of patients with splenomegaly achieving a response at Week 32 [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

Secondary Outcome Measures

  1. Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly) [4 years]

  2. Duration of response after achieving phlebotomy independence [4 years]

  3. Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome [32 weeks]

  4. Change from baseline of EORTC-QLQ-C30 patient-reported outcome [32 weeks]

Other Outcome Measures

  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]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 The Kirklin Clinic of UAB Hospital Birmingham Alabama United States 35249
2 University of Southern California Norris Comprehensive Cancer Center Los Angeles California United States 90033
3 Washington University School of Medicine Saint Louis Missouri United States 63110
4 Gabrail Cancer Center Canton Ohio United States 44718
5 The Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
6 Center Hospitalier Universitaire d'Angers Angers France 49933 Cedex 09
7 Universitätsklinikum Aachen Aachen Nordrhein-westfalen Germany
8 Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle Dresden Sachsen Germany
9 Universitätsklinikum Carl Gustav Carus Dresden Sachsen Germany
10 Stauferklinikum Schwäbisch Gmünd Mutlangen Germany 73557
11 Békés Megyei Központi Kórház Pándy Kálmán Tagkórház Gyula Hungary 5700
12 Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku Wrocław Dolnoslaskie Poland
13 Szpital Wojewódzki w Opolu Opole Poland 45-061
14 Hospital Universitario de Gran Canaria Doctor Negrin Las Palmas de Gran Canaria LAS Palmas Spain
15 Hospital Universitario Virgen de la Victoria Málaga Spain 29010
16 Hospital Universitario de Salamanca Salamanca Spain 37007

Sponsors and Collaborators

  • Kartos Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT03669965
Other Study ID Numbers:
  • KRT-232-102
First Posted:
Sep 13, 2018
Last Update Posted:
Jul 31, 2020
Last Verified:
Jul 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Polycythemia Vera
Polycythemia

Study Results

No Results Posted as of Jul 31, 2020