Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06456463




Registration number
NCT06456463
Ethics application status
Date submitted
31/05/2024
Date registered
13/06/2024
Date last updated
19/11/2024

Titles & IDs
Public title
A Study of Tagraxofusp in Combination with Venetoclax and Azacitidine in Adults with Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy
Scientific title
A Phase II Multicenter Open-label Trial of Tagraxofusp (Tag) in Combination with Venetoclax and Azacitidine (Ven/Aza) in Adults with Previously Untreated CD123+ Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy
Secondary ID [1] 0 0
2024-514660-48-00
Secondary ID [2] 0 0
STML-401-0423
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tagraxofusp
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine

Experimental: Part 1 - Tagraxofusp (9 µg/kg/day) - Participants will receive tagraxofusp in combination with venetoclax and azacitidine.

Experimental: Part 1 - Tagraxofusp (12 µg/kg/day) - Participants will receive tagraxofusp in combination with venetoclax and azacitidine.

Experimental: Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type - Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.

Experimental: Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated - Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.


Treatment: Drugs: Tagraxofusp
Tagraxofusp will be administered by intravenous infusion on days 4, 5, and 6 of each 28-day cycle.

Treatment: Drugs: Venetoclax
Venetoclax will be administered as an oral tablet (400 milligrams) daily of each 28-day cycle.

Treatment: Drugs: Azacitidine
Azacitidine will be administered subcutaneously or by intravenous infusion (75 milligrams/square meter) over 7 days of each 28-day cycle, per institutional guidelines/physician choice.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Determination of Part 2 Selected Dose of Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine
Timepoint [1] 0 0
Cycles 1-4 (up to 112 days; 28 days/cycle)
Primary outcome [2] 0 0
Part 2: Number of Participants Achieving a Best Overall Response (BOR) of Complete Remission (CR)
Timepoint [2] 0 0
Cycles 1-4 (up to 112 days; 28 days/cycle)
Secondary outcome [1] 0 0
Parts 1 and 2: Number of Participants Achieving a BOR of CR
Timepoint [1] 0 0
Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary outcome [2] 0 0
Parts 1 and 2: Time to First CR
Timepoint [2] 0 0
Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary outcome [3] 0 0
Parts 1 and 2: Duration of Response
Timepoint [3] 0 0
Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary outcome [4] 0 0
Parts 1 and 2: Number of Participants Achieving a BOR of CR, CR with Incomplete Hematologic Recovery (CRi), or CR with Partial Hematologic Recovery (CRh)
Timepoint [4] 0 0
Cycles 1-4 (up to 112 days; 28 days/cycle)
Secondary outcome [5] 0 0
Parts 1 and 2: Time to First Composite CR
Timepoint [5] 0 0
Cycles 1-4 (up to 112 days; 28 days/cycle)
Secondary outcome [6] 0 0
Parts 1 and 2: Number of Participants Achieving a BOR of CR or CRi
Timepoint [6] 0 0
Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary outcome [7] 0 0
Parts 1 and 2: Time to first CR/CRi
Timepoint [7] 0 0
Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary outcome [8] 0 0
Parts 1 and 2: Event-free Survival (EFS)
Timepoint [8] 0 0
Up to approximately 6 years
Secondary outcome [9] 0 0
Parts 1 and 2: CR with Minimal Residual Disease (MRD) Negative
Timepoint [9] 0 0
Cycles 1-6 (up to 168 days; 28 days/cycle)
Secondary outcome [10] 0 0
Parts 1 and 2: Number of Participants Who Bridged to Stem Cell Transplant (SCT) Through Study Treatment
Timepoint [10] 0 0
Up to approximately 6 years
Secondary outcome [11] 0 0
Parts 1 and 2: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine
Timepoint [11] 0 0
Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-6; 28 days/cycle)
Secondary outcome [12] 0 0
Parts 1 and 2: Number of Participants With Serum Anti-drug Antibodies for Tagraxofusp, Venetoclax, and Azacitidine
Timepoint [12] 0 0
Day 4 of each cycle (each cycle is 28 days) up to the end of study (approximately 6 years)
Secondary outcome [13] 0 0
Parts 1 and 2: Exposure-response of Free Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine
Timepoint [13] 0 0
Up to approximately 6 years

Eligibility
Key inclusion criteria
Key

* Previously untreated with histological confirmation of AML by World Health Organization criteria and are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity.
* Participant has any level of CD123 expression on blasts determined centrally by flow cytometry.
* Must be considered ineligible for intensive chemotherapy, defined by the following:

* =75 years of age; or
* =18 to 74 years of age with at least 1 of the following comorbidities:

* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3.
* Diffusing capacity of the lung for carbon monoxide of =65% or forced expiratory volume in 1 second =65%.
* Left ventricular ejection fraction =50%.
* Baseline creatinine clearance =30 to <45 milliliters/minute calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
* Hepatic disorder with total bilirubin >1.5 x upper limit of normal.
* Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Sponsor and Medical Monitor prior to enrollment.
* ECOG performance status:

* Of 0 to 2 for participants if =75 years of age, or
* Of 0 to 3 for participants =18 to 74 years of age.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has received prior therapy for AML.
* Willing and able to receive standard induction therapy.
* Treatment for an antecedent hematologic disease with any of the following:

* A hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine, intensive chemotherapy.
* Chimeric antigen receptor-T therapy or other experimental therapies.
* AML with central nervous system involvement.

Note: Other inclusion/exclusion criteria may apply.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
30/11/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
11/02/2030
Actual
Sample size
Target
76
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Townsville Hospital - Townsville
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [6] 0 0
St. Vincents Hospital - Fitzroy
Recruitment hospital [7] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [8] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4814 - Townsville
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
6000 - Perth
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Gyeonggi

Funding & Sponsors
Primary sponsor type
Other
Name
Stemline Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses of tagraxofusp (9 and 12 micrograms/kilogram/day \[µg/kg/day\]), used in combination with venetoclax and azacitidine, to determine the dose for Part 2. This determined dose, in combination with venetoclax and azacitidine, will then be further evaluated in Part 2 in 2 cohorts (TP53 mutated and TP53 wild type). Both parts will be conducted in participants with previously untreated CD123+ AML who are ineligible for intensive chemotherapy.
Trial website
https://clinicaltrials.gov/study/NCT06456463
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
Stemline Trials
Address 0 0
Country 0 0
Phone 0 0
1-877-332-7961
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/NCT06456463