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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03669965
Recruitment Status : Active, not recruiting
First Posted : September 13, 2018
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Study Description
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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
Polycythemia Vera Drug: KRT-232 Drug: Ruxolitinib Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
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 : January 15, 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : October 2022

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Arms and Interventions
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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
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Primary Outcome Measures :
  1. Proportion of patients with splenomegaly achieving a response at Week 32 [ Time Frame: 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) [ Time Frame: 4 years ]
  2. Duration of response after achieving phlebotomy independence [ Time Frame: 4 years ]
  3. Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome [ Time Frame: 32 weeks ]
  4. Change from baseline of EORTC-QLQ-C30 patient-reported outcome [ Time Frame: 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 [ Time Frame: 28 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03669965


Locations
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United States, Alabama
The Kirklin Clinic of UAB Hospital
Birmingham, Alabama, United States, 35249
United States, California
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
France
Center Hospitalier Universitaire d'Angers
Angers, France, 49933 Cedex 09
Germany
Universitätsklinikum Aachen
Aachen, Nordrhein-westfalen, Germany
Gemeinschaftspraxis Haematologie - Onkologie - Hauptstelle
Dresden, Sachsen, Germany
Universitätsklinikum Carl Gustav Carus
Dresden, Sachsen, Germany
Stauferklinikum Schwäbisch Gmünd
Mutlangen, Germany, 73557
Hungary
Békés Megyei Központi Kórház Pándy Kálmán Tagkórház
Gyula, Hungary, 5700
Poland
Dolnośląskie Centrum Transplantacji Komórkowych z Krajowym Bankiem Dawców Szpiku
Wrocław, Dolnoslaskie, Poland
Szpital Wojewódzki w Opolu
Opole, Poland, 45-061
Spain
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, LAS Palmas, Spain
Hospital Universitario Virgen de la Victoria
Málaga, Spain, 29010
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Sponsors and Collaborators
Kartos Therapeutics, Inc.
More Information
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Responsible Party: Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03669965    
Other Study ID Numbers: KRT-232-102
First Posted: September 13, 2018    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polycythemia Vera
Polycythemia
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
 Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders