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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04485260




Registration number
NCT04485260
Ethics application status
Date submitted
21/07/2020
Date registered
24/07/2020
Date last updated
9/05/2022

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
KRT-232-109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KRT-232
Treatment: Drugs - Ruxolitinib

Experimental: Part A, Arm 1, Cohort 1 - KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)


Treatment: Drugs: KRT-232
administered by mouth

Treatment: Drugs: Ruxolitinib
administered by mouth
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
Timepoint [1] 0 0
15 months
Primary outcome [2] 0 0
For Phase 2:To determine the spleen volume reduction (SVR) at Week 24
Timepoint [2] 0 0
6 months after last patient enrolled
Secondary outcome [1] 0 0
To determine spleen response
Timepoint [1] 0 0
43 months
Secondary outcome [2] 0 0
To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
Timepoint [2] 0 0
43 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2024
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Bulgaria
State/province [9] 0 0
Pleven
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Sofia
Country [11] 0 0
France
State/province [11] 0 0
Cedex 9
Country [12] 0 0
France
State/province [12] 0 0
Angers
Country [13] 0 0
France
State/province [13] 0 0
Le Mans
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Montpellier
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Tours
Country [18] 0 0
Germany
State/province [18] 0 0
Aachen
Country [19] 0 0
Germany
State/province [19] 0 0
Halle
Country [20] 0 0
Germany
State/province [20] 0 0
Jena
Country [21] 0 0
Germany
State/province [21] 0 0
Mainz
Country [22] 0 0
Germany
State/province [22] 0 0
Mutlangen
Country [23] 0 0
Israel
State/province [23] 0 0
Zerifin
Country [24] 0 0
Italy
State/province [24] 0 0
Bologna
Country [25] 0 0
Italy
State/province [25] 0 0
Catania
Country [26] 0 0
Italy
State/province [26] 0 0
Firenze
Country [27] 0 0
Italy
State/province [27] 0 0
Meldola
Country [28] 0 0
Italy
State/province [28] 0 0
Varese
Country [29] 0 0
Poland
State/province [29] 0 0
Kraków
Country [30] 0 0
Poland
State/province [30] 0 0
Opole
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Las Palmas De Gran Canaria
Country [33] 0 0
Spain
State/province [33] 0 0
Málaga
Country [34] 0 0
Spain
State/province [34] 0 0
Salamanca
Country [35] 0 0
Spain
State/province [35] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kartos Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04485260
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
John Mei
Address 0 0
Country 0 0
Phone 0 0
650-542-0136
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04485260