Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001656123p
Ethics application status
Submitted, not yet approved
Date submitted
15/10/2019
Date registered
27/11/2019
Date last updated
19/09/2025
Date data sharing statement initially provided
27/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
NHL34: An ALLG National Platform Study for Identification and Early Intervention in Ultra-High-Risk Large B Cell Lymphoma (CLARIFY)
Scientific title
NHL34: An ALLG National Platform Study (Master Protocol) for Identification and Early Intervention in Ultra-High-Risk Large B Cell Lymphoma (CLARIFY)
Secondary ID [1] 298640 0
NHL34 CLARIFY PROGNOSTIC
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Large B cell Lymphoma 313522 0
Condition category
Condition code
Cancer 311959 311959 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The NHL34 CLARIFY study is a multi-domain platform trial. This master protocol aims to offer real-time, centralized risk assessment for patients with Large B Cell Lymphoma (LBCL) who are treated with standard of care (SOC) immunotherapy. Patients will receive SOC regardless of the registration of this centralised and risk assessment platform trial.

Patients will have a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan and a Measurable Residual Disease (MRD) assay at baseline, cycle 4, cycle 6, and 3 months after treatment ends. Disease risk assessment will be determined based on centralised baseline tumour sequencing, centralised delta standardized uptake value (SUV) quantification / Deauville score and Measurable Residual Disease (MRD) by phased-variant ctDNA sequencing (PVSeq) at the specified serial time points. The PVSeq limit of detection (LOD) is approximately 1 part per 1,000,000. Outcomes of the dynamic biomarker assessment will be provided to the treating clinician in real-time by a standardised report from the coordinating central laboratory to inform of disease risk assessment and guide subsequent management.

This platform study will form the basis for patient screening and identify an ultra-high-risk (UHR) population. A weekly centralised review by the CLARIFY Prognostic Reference Committee (CPRC) meeting will occur to assess patient's eligibility to therapeutic treatment domains based on PVSeq assay and FDG-PET delta SUV / Deauville score. Patients who do not meet the criteria for a specific domain will be referred back to the master protocol.

Patients suitable for a therapeutic intervention from the NHL34 platform study must fulfill the eligibility criteria for the specific intervention.
Futility/failure of a treatment arm will be considered by the trial management committee and the ALLG safety and data monitoring committee in the event of any of the following:
1. Inadequate recruitment
2. Unacceptable toxicity
3. Evidence becoming available during the accrual phase of the trial, which clearly demonstrates that it is unethical to allocate patients to trial arms. The trial management committee will meet quarterly and the Safety and Data Monitoring Committee will review the patients registered to this platform annually.

The pharmacological investigational products for therapeutic arms will be selected based on a multi-tiered evaluation process designed to ensure scientific validity, participant safety, and regulatory compliance. The selection criteria includes scientific rationale, preclinical evidence, regulatory and ethical review. A CLARIFY working group, that consists of haematologists and research specialists, will meet quarterly to discuss potential therapeutic arms.

Interventions may include:
-CAR-T cell therapy (e.g. Axicabtagene Ciloleucel),
-Bispecific antibodies

Overall Study Duration.
Recruitment period: 2 years.
Participant follow-up: 24 months post end-of-induction (EoI).
Total study duration: Approximately 5 years.
Intervention code [1] 314904 0
Diagnosis / Prognosis
Intervention code [2] 314905 0
Treatment: Other
Comparator / control treatment
No control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 342833 0
To assess the feasibility of meeting the defined benchmarks for centralised MRD and FDG-PET review in real time. One of the defined benchmarks being: 21-days from the time of sample collection for MRD analysis and review to the date of report turnaround for MRD (all time-points excluding C2D15). The outcome will be assessed from the PET scan collection point and the MRD collection point to the time of return of results by the review committee. The time of return of results will be determined with an outcome notification letter by the CPRC committee that performs a weekly centralised review on the FDG-PET scans to SUV/Deauville scores.
Timepoint [1] 342833 0
At baseline, cycle 2 day 15, cycle 4 day 15, cycle 6 day 15, 3 months post EoT and 24 months post-EoT.
Primary outcome [2] 342834 0
To assess the feasibility of meeting the defined benchmarks for centralised MRD and FDG-PET review in real time. One of the defined benchmarks being: 7-days from the date of the FDG-PET scan to change in SUV / Deauville score FDG-PET report (only at C4D15, C6D15 and 3-months EoT timepoints). The outcome will be assessed from 7 day from the FDG-PET scan to SUV/Deauville score report. The time of return of results will be determined with an outcome notification letter by the CPRC committee that performs a weekly centralised review on the FDG-PET scans to SUV/Deauville scores.
Timepoint [2] 342834 0
At baseline, cycle 4 day 15, cycle 6 day 15 and 24 months post-EoT
Secondary outcome [1] 452301 0
The positive-predictive value (PPV) and negative-predictive value (NPV) will be determined as a measure of PVSeq performance, measured through peripheral blood (PB) MRD from circulating tumor DNA (ctDNA) samples
Timepoint [1] 452301 0
Within 24 months post end of induction (EOI) treatment.

Eligibility
Key inclusion criteria
1. Histologically confirmed diagnosis of CD20 positive large B cell lymphoma including diagnosis by 2022 WHO classification:
• DLBCL, not otherwise specified (NOS) including transformation from indolent lymphoproliferative disease
• T-cell/histiocyte-rich large B-cell lymphoma
• Epstein-Barr virus-positive DLBCL, NOS
• DLBCL/HGBCL with MYC and BCL2 rearrangements
• High-Grade B-Cell Lymphoma (HGBCL), NOS
• Follicular Large B Cell Lymphoma (FLBCL) (previously Grade 3B Follicular Lymphoma)
• High-risk pretreatment clinical prognostication by either
• Patients greater than 60-years: IPI Score greater than 3
• Patients less than 60-years: aaIPI Score 2-3
• Planned for frontline treatment with minimum 6 cycles of a combined immunochemotherapy regimen containing rituximab and anthracycline. These include: R-CHOP, DA-R-EPOCH, R-CHEOP, R-CHEP, R-Hyper-CVAD, Pola-R-CHP. Additional regimens may be approved on discussion with Co-PI
3. Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2
4. Ability to provide tumour tissue; archival or freshly collected
5. Aged greater than 18 years old at the time of screening
6. Life expectancy (due to non-lymphoma related reasons) of at least 6-months
7. Available for follow-up for 2-years post EoT
8. Can provide written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Histological subtypes of LBCL including mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; primary large B-cell lymphoma of immune-privileged sites; primary effusion DLBCL; primary cutaneous DLBCL, leg type; Post-Transplant Lymphoproliferative Disease
2. Primary or secondary CNS lymphoma at the time of recruitment to the study
3. Prior therapy for lymphoproliferative disease, with the exception of:
a. Corticosteroids (100mg or equivalent for less than 14 days)
b. Radiotherapy to target lesions as consolidation is allowed provided intent and anatomical location of consolidative radiotherapy is prespecified prior to or at enrolment. Radiation prior to enrolment is not permitted.
c. Central Nervous System (CNS) Prophylaxis (intrathecal or high-dose methotrexate) may be provided at treating clinician discretion as per local guidelines.
4. Pregnancy or lactation
5. Active synchronous solid tumour malignancy (excluding non-melanoma skin cancers and localised renal cell carcinoma)
6. Severe active infection.
7. Has any other clinically important abnormalities as determined by the recruiting investigator that may interfere with participation in or compliance with the study.
8. 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 to the 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This platform study will form the basis for patient screening and identify an ultra-high-risk (UHR) population. This platform aims to offer real-time, centralized risk assessment for patients and direct patients to therapeutic treatment domains they are eligible for.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/10/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 303180 0
Government body
Name [1] 303180 0
Medical Research Future Fund
Country [1] 303180 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
ALLG
34 Elizabeth St
Richmond
Vic 3121
Country
Australia
Secondary sponsor category [1] 303193 0
None
Name [1] 303193 0
Address [1] 303193 0
Country [1] 303193 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 303743 0
The Metro South Hospital and Health Service Human Reasearch Ethics Committee
Ethics committee address [1] 303743 0
Ethics committee country [1] 303743 0
Australia
Date submitted for ethics approval [1] 303743 0
01/03/2025
Approval date [1] 303743 0
Ethics approval number [1] 303743 0

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

Contacts
Principal investigator
Name 94642 0
Prof Maher Gandhi
Address 94642 0
Princess Alexandra Hospital Raymond Terrace, Mater Research Aubigny Place Level 3 South Brisbane Qld 4101
Country 94642 0
Australia
Phone 94642 0
+61 3 83739701
Fax 94642 0
Email 94642 0
[email protected]
Contact person for public queries
Name 94643 0
Delaine Smith
Address 94643 0
ALLG 35 Elizabeth St Richmond Vic 3121
Country 94643 0
Australia
Phone 94643 0
+61 03 83739701
Fax 94643 0
Email 94643 0
[email protected]
Contact person for scientific queries
Name 94644 0
Delaine Smith
Address 94644 0
ALLG 35 Elizabeth St Richmond Vic 3121
Country 94644 0
Australia
Phone 94644 0
+61 03 83739701
Fax 94644 0
Email 94644 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply that the requester must agree to before access is granted.


Conditions for requesting access:
• -

What individual participant data might be shared?
• De-identified IPD data for all data collected during the trial


What types of analyses could be done with individual participant data?
• Any type of analysis
Assessed on a case-by-case basis

When can requests for individual participant data be made (start and end dates)?
From:
Data available 3 months following publication, for an indefinite period


To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• Data sharing request system: Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol  [email protected] Access can be requested via the Health Data Austra... [More Details]


Results publications and other study-related documents

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

Documents added automatically
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