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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06479135




Registration number
NCT06479135
Ethics application status
Date submitted
21/06/2024
Date registered
28/06/2024
Date last updated
30/10/2024

Titles & IDs
Public title
Study of Navtemadlin Add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
Scientific title
A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib Vs Placebo Plus Ruxolitinib in JAK Inhibitor-Naïve Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
Secondary ID [1] 0 0
KRT-232-115
Universal Trial Number (UTN)
Trial acronym
POIESIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Post-PV MF 0 0
Post-ET Myelofibrosis 0 0
Primary Myelofibrosis 0 0
MF 0 0
Condition category
Condition code
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 - Navtemadlin
Treatment: Drugs - Navtemadlin placebo
Treatment: Drugs - Ruxolitinib

Experimental: Arm 1 - Navtemadlin administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.

Active comparator: Arm 2 - Navtemadlin placebo administered orally once daily on Days 1-7, off treatment on Days 8-28, in 28-day treatment cycles. Ruxolitinib administered orally twice a day.


Treatment: Drugs: Navtemadlin
Navtemadlin is an investigational MDM2 inhibitor

Treatment: Drugs: Navtemadlin placebo
Navtemadlin placebo

Treatment: Drugs: Ruxolitinib
Ruxolitinib is a janus kinase 1/2 inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To compare spleen volume reduction (SVR35) between Arm 1 and Arm 2
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
To compare total symptom score reduction (TSS50) between Arm 1 and Arm 2
Timepoint [2] 0 0
24 weeks
Secondary outcome [1] 0 0
To compare time to progression between Arm 1 and Arm 2
Timepoint [1] 0 0
Up to 8 years
Secondary outcome [2] 0 0
To compare overall survival (OS) between Arm 1 and Arm 2
Timepoint [2] 0 0
Up to 8 years

Eligibility
Key inclusion criteria
Inclusion Criteria for Ruxolitinib Alone Period:

* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
* High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* JAK-inhibitor treatment naive
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for Ruxolitinib Alone Period:

* Prior Splenectomy
* Splenic irradiation within 3 months prior to the first dose
* Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
* Eligible for Bone Marrow Transplant
* Peripheral blood or bone marrow blast count = 10 percent

Inclusion Criteria for Randomized Period:

* PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
* ECOG performance status of 0 to 2
* Treatment with a stable dose of ruxolitinib
* Suboptimal response to run-in ruxolitinib treatment

Exclusion Criteria for Randomized Period:

* Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10^9/L
* Peripheral blood or bone marrow blast count = 10 percent

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 receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
3/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2028
Actual
Sample size
Target
600
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Iowa
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Georgia
State/province [11] 0 0
Kutaisi
Country [12] 0 0
Georgia
State/province [12] 0 0
Tbilisi
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Busan
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Serbia
State/province [15] 0 0
Kragujevac
Country [16] 0 0
Serbia
State/province [16] 0 0
Novi Sad
Country [17] 0 0
Spain
State/province [17] 0 0
Malaga
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Gloucester
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Liverpool

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
jmei@kartosthera.com
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06479135