No registrations found.
ID
Source
Brief title
Health condition
recurrent / refractory malignant lymphomas
Sponsors and support
Intervention
Outcome measures
Primary outcome
Alteration / increase in interferon I and II (INF I and II) signatures in blood, measured 3 weeks after radiotherapy and after every 3 consecutive courses of immune checkpoint blockade. It is anticipated that the addition of radiotherapy will lead to an extra / more pronounced response.
Secondary outcome
-[18F]FDG PET-CT response 3 weeks after radiotherapy and after every 3 consecutive courses of ICB, related to the presence of 9p24.1 amplification. It is expected that lymphomas that harbour a 9p24.1 amplification and therefore an overexpression of PD-L1 will be more sensitive to (radio-) ICB therapy resulting in a more pronounced response.
-Changes in ctDNA, based on the presence of tumour-specific somatic genomic characterizations of the lymphoma; reflecting lymphoma activity or tumour cell death, measured 3 weeks after radiotherapy and after every 3 consecutive courses of ICB. After an initial increase, a larger decrease in ctDNA is expected in the irradiated group.
Background summary
The main objective of the study is enhancement of the immune response by radiation, and thereby treatment efficacy, in patients with recurrent / refractory malignant lymphomas treated with immune checkpoint blockade. As a measure for immune activation, interferon I and II signature alterations will be correlated with clinical response measured by [18F]FDG PET-CT scans and the amount of circulating tumour DNA (ctDNA).
Patients will be divided into 2 groups: A. 10 patients with recurrent / refractory 9p24.1 amplified malignant lymphomas and B. 10 patients with recurrent / refractory malignant lymphoma without 9p24.1 amplification. In both groups, patients are alternately assigned to treatment with immune checkpoint inhibition alone or radiation followed by immune checkpoint inhibition. In the group of patients that start with immune checkpoint inhibition alone, radiation will be implemented in the treatment at progression or insufficient response.
Study objective
Tumour cell disruption by radiation generates a surplus of neo-antigens that enhances the effect of immunotherapy in solid malignancies as well as malignant lymphomas. The hypothesis is that the combination of immune checkpoint inhibitors and radiation will lead to better responses and longer survival in patients with recurrent / refractory malignant lymphoma, compared with either modality given alone.
Study design
3 weeks after radiotherapy. After every 3 consecutive courses of immune checkpoint blockade.
Intervention
radiation
Inclusion criteria
- patients with refractory / recurrent malignant lymphoma eligible for immune checkpoint blockade therapy
- aged 18 – 75 year
- WHO score ≥2
- adequate organ function
- no prior treatment with checkpoint inhibitors
- no non-infectious pneumonitis requiring steroids
- not pregnant
- patients of childbearing / reproductive potential should use 2 birth control methods
- written informed consent
Exclusion criteria
- Not fit (mentally or physically) to undergo the proposed treatment.
- Patients with connective tissue diseases (inflammatory myopathy (polymyositis and ermatomyositis), systemic lupus erythematosus, Sjögren syndrome, systemic sclerosis, antisynthetase syndrome, rheumatoid arthritis, severe psoriasis and mixed CTDs), vasculitis (granulomatosis with polyangiitis (Wegener’s granulomatosis), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), severe Behçet disease, Takayasu arteritis, giant cell arteritis, Buerger disease, Kawasaki disease, polyarteritis nodosa, severe immunoglobulin A (IgA) vasculitis (Henoch–Schönlein purpura), severe cutaneous vasculitis, polymyalgia rheumatica, severe cryoglobulinaemia and undifferentiated systemic vasculitis) and other autoimmune diseases (primary biliary cirrhosis, severe autoimmune hepatitis, multiple sclerosis, severe antiphospholipid syndrome, myasthenia gravis, Guillain–Barré syndrome, inflammatory bowel disease, Miller–Fisher syndrome, Vogt–Koyanagi–Harada syndrome, eosinophilic fasciitis (Shulman syndrome), relapsing polychondritis and severe autoinflammatory diseases) ( Martins et al. 2019).
- Sensory or motor peripheral neuropathy > grade 2.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9091 |
| CCMO | NL75774.091.21 |
| OMON | NL-OMON50953 |