patients with recurrent / refractory 9p24.1 amplified malignant lymphomas patients with recurrent / refractory malignant lymphoma without 9p24.1 amplification MedDRA version: 20.0 Level: PT Classification code 10025310 Term: Lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Opdivo
Product Name: Opdivo
Product Code: EMEA/H/C/003985
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: KEYTRUDA
Product Name: KEYTRUDA
Product Code: EMEA/H/C/00
Sponsors
Radboud University Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - patients with refractory / recurrent malignant lymphoma eligible for ICB therapy - aged 18 – 75 year - WHO score =2 - adequate organ function: neutrophil count, serum creatinine, ASAT, ALAT, albumin - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
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 outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Enhancement of the immune response (with Optivo or Keytruda) by radiation, and thereby treatment efficacy, in patients with recurrent / refractory malignant lymphomas treated with ICB. As a measure for immune activation, INF I and II signature alterations will be correlated with clinical response measured by standard [18F]FDG PET-CT scans and ctDNA in blood.;Secondary Objective: -To correlate the presence of 9p24.1 in the tumour with response to (radio-) checkpoint blockade immune therapy (CBIT). -To investigate tumour mutational burden as a measure for tumor antigens and neo-antigens. -To investigate the T-cell receptor repertoire as response to the increase in tumour antigens and neoantigens, and in relation to treatment. -To investigate whether and which additional factors influence and reveal the immune response (changes in blood leukocyte subsets, functional T- and NK-cell assays, gut microbiome). -To correlate ‘myeloid regulatory cell number and function’ with immune response as measured by [18F]FDG PET-CT scans and the amount of ctDNA. -Comparison of therapy response of irradiated and non-irradiated lesions in the same patient (abscopal effect). --To investigate whether re-treatment with radio-immunotherapy will undo checkpoint inhibition resistance in patients who show progression in the study protocol.;Primary end point(s): Enhancement of the immune response by radiation, and thereby treatment efficacy, in patients with relapsed / refractory malignant lymphomas treated with immune checkpoint inhibition. As a measure for immune activation, interferon I and II signature alterations will be correlated with clinical response using standard [18F]FDG PET-CT scans and ctDNA measurements in blood.;Timepoint(s) of evaluation of this end point: a) 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 ICB. b) FDG PET-CT response 3 weeks after radioth | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To correlate amplification of 9p24.1 in malignant lymphoma with response to (radio-) immune checkpoint inhibition therapy. The 9p24.1 amplification contains several genes; we focus mainly on the genes PDCD1LG1 (encoding programmed cell death 1 ligand 1) and PDCD1LG2 (encoding programmed cell death 1 ligand 2). - To correlate tumour mutational burden with response to treatment. - To investigate additional factors either influencing or revealing the immune response: changes in blood leukocyte subsets, T-cell receptor repertoire, functional T- and NK-cell assays, gut microbiome. - To correlate ‘myeloid regulatory cell number and function’ with immune response as measured by [18F]FDG PET-CT scans and the amount of ctDNA. - To compare, using [18F]FDG PET-CT scans, irradiated and non-irradiated lesions in the same patient (abscopal effect). - To investigate whether re-treatment with radio-immune checkpoint blockade will undo checkpoint inhibition resistance in patients who show progression in the study protocol.;Timepoint(s) of evaluation of this end point: 3 weeks after radiotherapy and after every 3 consecutive courses of ICB | — |
Countries
Netherlands
Contacts
Public ContactProjectleader
Radboud University Medical Centre
Outcome results
None listed