Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000429459
Ethics application status
Approved
Date submitted
2/10/2024
Date registered
9/05/2025
Date last updated
22/06/2025
Date data sharing statement initially provided
9/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A Centralized Platform study for Functional High Risk Multiple Myeloma - Master Protocol
Scientific title
A Centralized Platform study for Functional High Risk Multiple Myeloma - Master Protocol
Secondary ID [1] 313088 0
AMaRC 24-01
Universal Trial Number (UTN)
Trial acronym
ZEPFHR-MM
Linked study record
Refer to ANZCTR records for each individual domain under ZEPFHR-MM Master Protocol:
Domain 1 - Talquetamab and Teclistamab: ACTRN12625000438459

Health condition
Health condition(s) or problem(s) studied:
Myeloma 335330 0
Relapsed refractory myeloma 335332 0
Multiple myeloma 335331 0
Condition category
Condition code
Cancer 331904 331904 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Indication: All participants across all domains will have the same primary indication/inclusion criteria: Participant has functional high-risk myeloma, which is defined has having relapsed within 18 months of initiating treatment for multiple myeloma.

Domain selection for partipicants: There will be multiple domains within this platform study. Each domain will be independent of each other. Domains will be activated based on site preference/clinical need for local population. Site investigators will choose which domain/intervention a participant will enrol into based on investigator’s assessment.

Duration of treatment/domain: Participants will be treated until progression, unless specified otherwise (e.g: Fixed duration treatment). All participants will be monitored per 28-day cycle unless specified otherwise (e.g: intervention required >28 day cycles) and will involve blood tests, bone marrow samples and imaging as needed.

Duration of platform study: It is predicted that the overall platform study will be at least 5 years.

Domains may be closed due to safety concerns, treatment futility or operational futility
Intervention code [1] 329645 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339518 0
To demonstrate the efficacy of a treatment regimen in FHR MM patients or, a specific subpopulation (or domain) of these patients.
Timepoint [1] 339518 0
Achievement of a partial response (PR) or better at any time within the first four cycles of treatment, assessed at Cycle 5 unless participant comes of treatment earlier.
Secondary outcome [1] 442883 0
To obtain an estimate of Event-free survival (PFS)
Timepoint [1] 442883 0
Measured from the date of first dose of study drug until the earliest of the dates of withdrawal for any reason, PD or death, whichever comes first. This will be assessed from Cycle 1 Day 1, at day 1 of each subsequent cycle until the disease progression. There is no time limit.
Secondary outcome [2] 440300 0
To obtain an estimate of the Duration of response (DoR)
Timepoint [2] 440300 0
Measured from the date that a response of PR or better is first achieved until the date that response is lost. Response will be measured day 1 of each cycle until the disease progression. There is no time limit.
Secondary outcome [3] 442881 0
To obtain an estimate of the Time to progression (TTP)
Timepoint [3] 442881 0
Measured from the date of first dose of study drug until the date that progressive disease is first observed. This will be assessed from Cycle 1 Day 1, at day 1 of each subsequent cycle until the disease progression. There is no time limit.
Secondary outcome [4] 442882 0
To obtain an estimate of Progression-free survival (PFS)
Timepoint [4] 442882 0
Measured from the date of first dose of study drug until the earlier of the date that progressive disease (PD) is first observed or the date of death. Response will be measured day 1 of each cycle until the disease progression. There is no time limit.

Eligibility
Key inclusion criteria
- Age >= 18 years of age.
- Able to provide written consent.
- Documented diagnosis of MM with measurable disease as define by any of the following
- Serum M-component greater than 5 g per L and/or
- Urine M-component greater than200 mg per 24 h, and/or
- Involved serum free light chain level greater than 100mg per L.
- Patients who do not meet these criteria but have biopsy proven extra-medullary disease (extra-osseous plasmacytoma that is not contiguous with an osseous plasmacytoma) that can undergo response evaluation with serial PET-CT are considered to have measurable disease.
- Documented evidence of progressive disease within 18 months of commencing front-line therapy for newly diagnosed MM according to IMWG response criteria
- Patients must have received only 1 prior therapy consisting of an IMID or PI-based induction regimen with or without high dose melphalan conditioned autologous stem cell transplant +/- lenalidomide maintenance.
- No contraindication to the use of any of the study drugs and able to comply with trial requirements.
Adequate liver function (total bilirubin less than 2.0x upper limit of normal (ULN), alanine aminotransferase less than 5.0x ULN) unless considered secondary to MM.
- Absolute neutrophil count greater than or equal to 1.0 x 109 per L. Granulocyte colony-stimulating factor (G-CSF) therapy is permitted on study.
Platelet count greater than or equal to 50 x 109/L (greater than or equal to 30 x 109 per L if MM involvement in the marrow is greater than 50 per cent), patients should not have received platelet transfusions within 7 days of the screening platelet count.
- Hb greater than or equal to 80g per L, red cell transfusions as per institutional protocol are allowed.
- Has provided written informed consent.
- Women of childbearing potential participants must not become pregnant while on study; male participants must not father children while on study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients who have had myocardial infarction within 6 months prior to enrolment, or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Any other serious or uncontrolled medical or psychiatric illness that could, in the investigators’ opinion, potentially interfere with the completion of treatment according to this protocol.
- Known ongoing or active systemic infection, active hepatitis B or C infection, or known human immunodeficiency virus positivity. Patients with latent TB can proceed on study provided adequate prophylaxis has been commenced.
- Known autoimmune disease requiring ongoing immunosuppression
- Women who are pregnant or lactating. Women of child-bearing potential must have a negative pregnancy test (minimum sensitivity of at least 25 mIU per mL) at Screening.
- Active malignancy with the exception of any of the following:
o Adequately treated basal cell carcinoma, squamous cell carcinoma or in situ cervical cancer.
o Adequately treated stage 1 cancer from which the subject is currently in remission from and has been in remission for greater than 2 years.
o Stage 1 prostate cancer that does not require treatment.
o Any other cancer from which the subject has been disease-free for greater than 2 years.
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
- Participation in other clinical trials for the treatment of MM, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Platform trial i.e multiple, individual platforms. Assignment based on availability and treating investigator decision
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
11/06/2025
Actual
11/06/2025
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 27852 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [2] 27175 0
The Alfred - Melbourne
Recruitment hospital [3] 27851 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 27176 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [5] 27853 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [6] 27177 0
Box Hill Hospital - Box Hill
Recruitment hospital [7] 27854 0
Concord Repatriation Hospital - Concord
Recruitment hospital [8] 27855 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 44046 0
2170 - Liverpool
Recruitment postcode(s) [2] 43257 0
3004 - Melbourne
Recruitment postcode(s) [3] 44048 0
2298 - Waratah
Recruitment postcode(s) [4] 44047 0
3220 - Geelong
Recruitment postcode(s) [5] 44050 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 43259 0
3128 - Box Hill
Recruitment postcode(s) [7] 44049 0
2139 - Concord
Recruitment postcode(s) [8] 43258 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 317532 0
Government body
Name [1] 317532 0
Australian Government Department of Health and Aged Care: Medical Research Future Fund
Country [1] 317532 0
Australia
Funding source category [2] 317533 0
Other Collaborative groups
Name [2] 317533 0
Australasian Myeloma Research Consortium
Country [2] 317533 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Myeloma Research Consortium
Address
Country
Australia
Secondary sponsor category [1] 319837 0
None
Name [1] 319837 0
Address [1] 319837 0
Country [1] 319837 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316244 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 316244 0
Ethics committee country [1] 316244 0
Australia
Date submitted for ethics approval [1] 316244 0
23/09/2024
Approval date [1] 316244 0
27/11/2024
Ethics approval number [1] 316244 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137266 0
Prof Andrew Spencer
Address 137266 0
Alfred Health, 55 Commercial Road, MELBOURNE VIC 3004
Country 137266 0
Australia
Phone 137266 0
+61 3 9076 3393
Fax 137266 0
Email 137266 0
[email protected]
Contact person for public queries
Name 137267 0
Khoa Le
Address 137267 0
Level 2, South Block, Alfred Health, 55 Commerical Road, Melbourne VIC 3004
Country 137267 0
Australia
Phone 137267 0
+61 3 9076 7851
Fax 137267 0
Email 137267 0
[email protected]
Contact person for scientific queries
Name 137268 0
Prof. Andrew Spencer
Address 137268 0
Level 2, South Block, Alfred Health, 55 Commerical Road, Melbourne VIC 3004
Country 137268 0
Australia
Phone 137268 0
+61 3 9076 7851
Fax 137268 0
Email 137268 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.