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Trial registered on ANZCTR
Registration number
ACTRN12624001105538p
Ethics application status
Not yet submitted
Date submitted
28/08/2024
Date registered
13/09/2024
Date last updated
13/09/2024
Date data sharing statement initially provided
13/09/2024
Type of registration
Prospectively registered
Titles & IDs
Public title
Understanding the Abscopal Effect of Low-Dose Localised Radiotherapy in Follicular Lymphoma: The AFL study
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Scientific title
Understanding the Abscopal Effect of Involved-Site Radiotherapy in Patients with Follicular Lymphoma Aged 40 years and over: The AFL study
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Secondary ID [1]
312830
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None
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Universal Trial Number (UTN)
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Trial acronym
The AFL Study
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma
334897
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Condition category
Condition code
Cancer
331478
331478
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0
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Consented patients with Follicular Lymphoma (either disease recurrence or slow growing/stable lymphoma) in more than one site of disease will receive low dose localised radiotherapy (involved-site radiotherapy or ISRT) to some (not all) of their known lymphoma disease sites at the discretion of the treating radiation oncologist.
Along with standard of care FDG-PET/CT scans prior to radiotherapy (within 60 days), a single 89Zr-durvalumab PET/CT and two (at 1-2 hours and 24 hours post 89Zr- IAB22M2C infusion) 89Zr- IAB22M2C PET/CT scans will be performed – all given over a 5-10 minute infusion and each scan will take 30-45 mins spent on the PET/CT scanner. Patients will be administered 3.0mCi/8ml of89Zr- IAB22M2C during the infusion using a syringe pump. 10 mg of unlabeled durvalumab will be infused over 30 min. After 60 min of observation, the patient will receive 89Zr-durvalumab (60 mBq/70 k up to no more than 74MBq with a concentration of 4 ug/MBq). All PET scans will be acquired according to current departmental guidelines on an integrated PET/CT. This will be reported by a qualified PET physician who will also administer these tracers. The delayed timing of PET image acquisition (4-5 days after tracer administration) is due to the long physical and physiological half-lives of the tracer, and timing.
20ml routine and study blood samples will also be taken at this timepoint. Then, ISRT will be delivered to lesions that are selected and will receive 4 Gy in 2 fractions, delivered on consecutive days. 2 weeks post ISRT, study and routine bloods will be collected along with another two 89Zr- IAB22M2C PET/CT scan’s (again 1-2 hrs and 24hrs post infusion). Lastly, at 6-8 weeks post ISRT, standard of care bloods will be collected along with standard management FDG-PET scans. Following completion of the imaging and pathology phase of the study participants will return to standard of care follow up with their radiation oncologist and/or haematologist approximately 3 months post involvement.
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Intervention code [1]
329356
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Diagnosis / Prognosis
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Comparator / control treatment
No control group
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Control group
Uncontrolled
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Outcomes
Primary outcome [1]
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Composite primary outcome: Local abscopal response per lesion or nodal station on FDG-PET and overall (whole body abscopal response on FDG PET)
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Assessment method [1]
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Local abscopal response per lesion or nodal station on FDG-PET:
Complete metabolic response (CMR). This is defined by a Deauville score of 1-3, for lesions with initial intensity > liver.
Partial metabolic response (PMR)
Stable metabolic disease (SMD).
Progressive metabolic disease PMD
Overall (whole body) abscopal response on FDG PET (CMR & PMR)
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Timepoint [1]
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Baseline (pre-treatment) and follow up FDG-PET imaging 6 weeks after ISRT
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Secondary outcome [1]
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Uptake of tracer in each known lymphoma site
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Assessment method [1]
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All CD8 and PD-L1 imaging will be assessed for biodistribution and tumour uptake of IAB22M2C based on qualitative and dosimetry (SUVmax) analysis. Blood counts, results of translational blood analyses and biopsy results will also be used as assessment methods.
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Timepoint [1]
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At baseline and 2-6 weeks post ISRT, translational bloods will be collected and CD8 and PD-L1 imaging will be assessed.
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Eligibility
Key inclusion criteria
1) Eligible to receive palliative ISRT for histologically confirmed low grade (WHO grade1,2 or 3a) follicular lymphoma,
2) Requiring ISRT to local disease for palliation or prevention of local disease progression, or eligible for a “watchful waiting” approach to management
3) >2 lymphoma lesions visualized on FDG-PET scan, with FDG uptake > liver (not including spleen or bone marrow disease)
4) >1 FDG-avid lesion(s) located outside planned ISRT volume, with FDG uptake > liver (not including spleen or bone marrow disease)
5) No systemic therapy (chemo or immunotherapy) delivered in the 2 months before radiation therapy
6) No systemic therapy planned for at least 2 months after ISRT
7) Capable of giving informed consent
8) Life expectancy > 12 months
9) ECOG performance status 0-1 (or 2 if impairment is not related to lymphoma)
10) Available FFPE biopsy specimen confirming diagnosis of FL, suitable for translational studies
11) Age >40
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Minimum age
40
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1) Initial presentation of stage II disease suitable for curative intent RT
2) Any active high grade lymphoma
3) Any prior history of aggressive or transformed lymphoma
4) >2 prior systemic therapy regimens
5) Taking any immunosuppressive medication (e.g. steroids)
6) Active autoimmune disease
7) Neutropaenia (<1.0 x 109)
8) All FDG-avid disease sites are considered to be high priority for early treatment with ISRT and no lesion can safely be left untreated
9) Irradiation of a lesion selected for ISRT would inadvertently irradiate all nominally “untreated” lesions, intended for observation, to > 0.4 Gy
10) Palliative ISRT is required within 7 days for rapid symptom relief
11) Women who are pregnant or who are breastfeeding
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Not Applicable
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Type of endpoint/s
Bio-availability
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Statistical methods / analysis
The primary endpoint is the abscopal regression rate. This is the proportion of patients who after ISRT experience regression of any unirradiated, previously FDG-avid lymphoma lesions, as detected on follow up FDG-PET imaging 6 weeks after ISRT. The abscopal regression rate will be assessed both per lesion/nodal station and overall per patient as follows.
Local abscopal response per lesion or nodal station on FDG-PET; Complete metabolic response (CMR) defined by a Deauville score of 1-3, Partial metabolic response (PMR) analysed by a visually appreciable reduction in FDG uptake, therefore reduction of SUV max, stable metabolic disease (SMD) or progressive metabolic disease (defined by Deauville score of 4 or 5).
Overall (whole body) abscopal response on FDG PET will also be analysed by:
Allocating patients to one of the following overall abscopal response categories based on a consideration of all disease sites in pre and post treatment FDG-PET scans.
a) Complete abscopal response: CMR in all unirradiated lesions and no new lesions
b) Partial abscopal response: at least a PMR in all unirradiated lesions but without a CMR in all unirradiated lesions and no new lesions
b) Mixed abscopal response: CMR or PMR in one or more unirradiated lesions but SMD, or PMD in any other lesion(s). May have one or more new lesions.
c) No abscopal response: No CMR or PMR in any unirradiated lesion
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Recruitment
Recruitment status
Not yet recruiting
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Date of first participant enrolment
Anticipated
1/01/2025
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Actual
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Date of last participant enrolment
Anticipated
1/01/2027
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Actual
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Date of last data collection
Anticipated
1/04/2027
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Actual
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Sample size
Target
10
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC
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Funding & Sponsors
Funding source category [1]
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Commercial sector/Industry
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Name [1]
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Varian
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Address [1]
317253
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Country [1]
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Australia
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Primary sponsor type
Hospital
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Name
Peter MacCallum Cancer Centre
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Address
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Country
Australia
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Secondary sponsor category [1]
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None
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Name [1]
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Address [1]
319547
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Country [1]
319547
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Ethics approval
Ethics application status
Not yet submitted
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Ethics committee name [1]
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Peter MacCallum Cancer Centre Human Research Ethics Committee
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Ethics committee address [1]
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https://www.petermac.org/research/doing-research-us/ethics-governance
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Ethics committee country [1]
315989
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Australia
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Date submitted for ethics approval [1]
315989
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01/11/2024
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Approval date [1]
315989
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Ethics approval number [1]
315989
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Summary
Brief summary
This study is investigating if low-dose localised radiotherapy (involved-site radiation therapy or “ISRT”) can sometimes activate the immune system to cause shrinkage or even disappearance of disease in other parts of the body, outside of the treated region, in patients with advanced Follicular lymphoma (FL) Patients in this study will receive very low dose radiotherapy to some, but not all, of their known lymphoma disease sites. This trial will systematically explore the potential of low dose ISRT as a single modality to engage anti-tumour immunity in advanced FL through investigating both the frequency and the biology of abscopal regression in FL. It will utilise serial imaging and correlative analyses with serial blood (+/- tissue) samples, to explore the underlying mechanisms that may be responsible for this important phenomenon. Who is it for? This study is open both to patients who have had recurrence of disease after previous treatments, and patients who have slow growing or stable lymphoma that would be otherwise be managed by close observation without any current active therapy. You must be aged 40 and over. Study details All participants will undergo a Positron Emission Tomography (PET)/Computed Tomography (CT) with fluoro-deoxyglucose (FDG) which is a standard type of scan to detect FL. PET scanning is performed by injecting a small amount of radioactive material (called a tracer) into your bloodstream followed by imaging your body by passing you through a PET/CT scanner. As well as standard FDG-PET scans, this study will involve the use of two new PET scan tracers that allow us to see different aspects of the immune system. These tracers are called 89Zr- IAB22M2C and 89Zr-durvalumab respectively. They need 1- 5 days to be taken up in the tumour after injection and therefore PET imaging scans are performed 1-5 days after the tracer is given. PET scanning with 89Zr-IAB22M2C allows CD8+ T lymphocytes to be tracked in the body. CD8 T cells can be involved in killing tumour cells in patients with cancer and there is evidence from laboratory studies that CD8 T cells accumulate in tumours before abscopal regression occurs. The other new tracer, 89Zr-durvalumab, enables a molecule called PD-L1 to be imaged in patients. PD-L1 is a target for Immune Checkpoint Immunotherapy and can be found on some tumour cells and on cells of the immune system. Using these novel PET tracers we hope to increase our understanding of the effects of radiation on immunity in general and on the abscopal effect in particular.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Prof Michael MacManus
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Address
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Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne Victoria 3000
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Country
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Australia
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Phone
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+61 03 8559 7761
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Fax
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Email
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[email protected]
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Contact person for public queries
Name
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Michael MacManus
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Address
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Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne Victoria 3000
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Country
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Australia
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Phone
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+61 03 8559 7761
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Name
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Michael MacManus
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Address
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Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne Victoria 3000
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Country
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Australia
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Phone
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+61 03 8559 5000
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Fax
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Email
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[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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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.
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