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Trial record 2 of 2 for:    krt-232

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

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ClinicalTrials.gov Identifier: NCT03669965
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

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 3 arms with 2 different doses and 2 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 295 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
Estimated Study Start Date : October 31, 2018
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : October 2023


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




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 ]


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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

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


Contacts
Contact: John Mei 6505420136 jmei@kartosthera.com

Locations
United States, California
Innovative Clinical Research Institute Recruiting
Whittier, California, United States, 90603
Contact: Kirsten Bettino    562-693-4477    kbettino@airesearch.us   
United States, Florida
University Cancer Institute Recruiting
Boynton Beach, Florida, United States, 33426
Contact: Paula Ortiz    561-737-6556    portiz@universitycancerinstitute.com   
United States, New Jersey
Summit Medical Group Recruiting
Florham Park, New Jersey, United States, 07932
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Carrie Smith    330-492-3345 ext 208    csmith@gabrailcancercenter.com   
Sponsors and Collaborators
Kartos Therapeutics, Inc.
Investigators
Study Director: Thomas Jahn, MD, PhD Kartos Therapeutics, Inc.

Responsible Party: Kartos Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03669965     History of Changes
Other Study ID Numbers: KRT-232-102
First Posted: September 13, 2018    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders