None listed
Conditions
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.
Interventions
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- IAB22M
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.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
40 Years to No maximum
Healthy volunteers
No
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
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
Outcome results
None listed