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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03662126




Registration number
NCT03662126
Ethics application status
Date submitted
5/09/2018
Date registered
7/09/2018
Date last updated
28/04/2023

Titles & IDs
Public title
KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment
Scientific title
A Phase 2/3 Randomized, Controlled, Open-Label Study of KRT 232 in Subjects With Primary Myelofibrosis (PMF), Post Polycythemia Vera MF (Post-PV-MF), Or Post Essential Thrombocythemia MF (Post-ET-MF) Who Are Relapsed or Refractory to Janus Kinase (JAK) Inhibitor Treatment
Secondary ID [1] 0 0
KRT-232-101
Universal Trial Number (UTN)
Trial acronym
BOREAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis (PMF) 0 0
Post-Polycythemia Vera MF (Post-PV-MF) 0 0
Post-Essential Thrombocythemia MF (Post-ET-MF) 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 - Best Available Therapy (BAT)

Experimental: Part A Cohort 1 - KRT-232 120 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

Experimental: Part A Cohort 2 - KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)

Experimental: Part A Cohort 3 - KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Experimental: Part A Cohort 4b - KRT-232 240 mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)

Experimental: Part B Arm 1 KRT-232 - KRT-232 240 mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)

Active comparator: Part B Arm 2 Best Available Therapy - Best available therapy at the discretion of the investigator, on a 28-day cycle.


Treatment: Drugs: KRT-232
KRT-232, administered by mouth

Treatment: Drugs: Best Available Therapy (BAT)
Best available therapy options include:

1. hydroxyurea
2. chemotherapy or
3. supportive care (including but not limited to corticosteroids and androgens; JAK inhibitors not allowed).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
(Part A Only) Spleen Volume Reduction (SVR)
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
(Part B Only) Spleen Volume Reduction (SVR)
Timepoint [2] 0 0
24 Weeks
Secondary outcome [1] 0 0
(Part A only) Improvement in Total Symptom Score (TSS)
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
(Part B only) Improvement of Total Symptom Score (TSS)
Timepoint [2] 0 0
24 Weeks
Secondary outcome [3] 0 0
(Part B only) Overall Survival (OS)
Timepoint [3] 0 0
48 months
Secondary outcome [4] 0 0
(Part B only) Progression free survival (PFS)
Timepoint [4] 0 0
48 months
Secondary outcome [5] 0 0
(Part B Only) Overall Spleen Volume Reduction (SVR)
Timepoint [5] 0 0
48 months
Secondary outcome [6] 0 0
(Part B Only) Spleen Response Duration
Timepoint [6] 0 0
48 months
Secondary outcome [7] 0 0
(Part B Only) Rate of conversion from RBC transfusion dependent to independent
Timepoint [7] 0 0
24 weeks

Eligibility
Key inclusion criteria
* Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
* High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
* Failure of prior treatment with JAK inhibitor
* ECOG = 2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior splenectomy
* Splenic irradiation within 3 months prior to randomization
* History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization
* History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization
* Prior MDM2 inhibitor therapy or p53-directed therapy
* Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant
* History of major organ transplant
* Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
385
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
Fiona Stanley Hosital - Murdoch
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
South Eastern Private Hospital - Noble Park
Recruitment hospital [6] 0 0
Icon Cancer Center - South Brisbane
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
6150 - Murdoch
Recruitment postcode(s) [3] 0 0
- Adelaide
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- Melbourne
Recruitment postcode(s) [5] 0 0
3174 - Noble Park
Recruitment postcode(s) [6] 0 0
- South Brisbane
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kartos Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with a JAK inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.

This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT (Arm 2). The BAT administered will be determined by the treating physician, with the option to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any time.
Trial website
https://clinicaltrials.gov/study/NCT03662126
Trial related presentations / publications
Al-Ali, H.K.; Delgado, R.G.; Lange, A.; Pluta, A.; McLornan, D.; Vachhani, P.; Damaj, G.L.; Jost, P.J.; Rejto, L.; Hus, M.; et al. KRT-232, A First-In-Class, Murine Double Minute 2 Inhibitor, for Myelofibrosis Relapsed or Refractory to Janus-Associated Kinase Inhibitor Treatment. Eha. Libr. 2020, 295035, S215
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/NCT03662126