An Open-Label, Multicenter, Phase 1b/2 Study of the Safet... | NCT04485260

Studies
An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib

NCT04485260

Sponsor

Kartos Therapeutics, Inc.

Status

Unknown status

Last Update Posted

May 9, 2022Actual

Enrollment

36Estimated

Phase

Phase 1Phase 2

Conditions

Myelofibrosis

Interventions

KRT-232
Ruxolitinib

Countries

United States
Australia
Bulgaria
France
Germany
Israel
Italy
Poland
Spain

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Brief Title

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib

Official Title

Status Module

Record Verification Date

May 2022

Overall Recruitment Status or Expanded Access Status

Unknown status

Last Known Status

Recruiting

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Jan 28, 2021Actual

Primary Completion Date

Oct 2022Estimated

Completion Date

Oct 2024Estimated

First Submitted Date

Jul 21, 2020

First Submission Date that Met QC Criteria

Jul 21, 2020

First Posted Date

Jul 24, 2020Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

May 5, 2022

Last Update Posted Date

May 9, 2022Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Not provided

Is FDA Regulated Drug

Yes

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief Summary

This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in combination with ruxolitinib.

Detailed Description

Not provided

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

36Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part A, Arm 1, Cohort 1	Experimental	KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)	Drug: KRT-232 Drug: Ruxolitinib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
KRT-232	Drug	administered by mouth	Part A, Arm 1, Cohort 1
Ruxolitinib

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib	Dose limiting toxicities will be used to establish the MTD of KRT-232 in combination with ruxolitinib. Subsequently, RP2D will be based on safety and efficacy data of the combination.	15 months
For Phase 2:To determine the spleen volume reduction (SVR) at Week 24	The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan	6 months after last patient enrolled

Secondary Outcomes

Measure	Description	Time Frame
To determine spleen response	The proportion of subjects achieving ≥35% SVR at any time point from Baseline while on study, as assessed by MRI (or by CT scan for applicable subjects)	43 months
To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO)
Treatment with ruxolitinib for ≥18 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to study entry
Spleen ≥5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT
Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0
ECOG performance status of 0 to 2

Exclusion Criteria:

Patients who are positive for TP53 mutations
Documented disease progression or clinical deterioration any time while on ruxolitinib treatment
Patients who have had a documented spleen response to ruxolitinib.
Prior splenectomy
Prior MDM2 inhibitor therapy or p53-directed therapy

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

99 Years

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Name	Role	Phone	Extension	Email
John Mei	Contact	650-542-0136		jmei@kartosthera.com

Overall Officials

Not provided

Locations

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope	Recruiting	Duarte	California	91010	United States
John Hopkins University

Derived Section

Miscellaneous Info Module

Version Holder

Jul 10, 2026

Removed Countries

Not provided

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

MeSH Terms

Intervention Browse Module

MeSH Terms

ID	Term
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
C000723723	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
C540383	ruxolitinib