Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin's lymphoma and is often diagnosed in advanced incurable stage. In our previous trail, Lymvac-1, patients were treated with sequential intratumoral injections of low-dose rituximab and autologous dendritic cells, combined with local radiotherapy at the same site. The aim was to overcome tumor tolerance. In this trial, clinical responses correlated strongly with systemic anti-tumor CD8+ T-cell responses detected in blood after therapy. The primary aim of the planned study (Lymvac-2) is to significantly improve rates of immunological and clinical responses by adding iv anti-PD-1 antibody (Pembrolizumab) relative to the cohort of patients previously treated with intranodal immunotherapy without Pembrolizumab (Lymvac-1). The study includes 10 patients with untreated or relapsed FL.
Patients with advanced stage follicular lymphoma, untreated and relapsed are eligible for this study. Staging includes PET/CT, CT and bone marrow specimens. Lymphoma nodes must be available for surgical biopsy, radiation and intranodal treatment. Additionally, there must be evaluable lesions for measuring systemic effects. The patient undergo leukapheresis for collection of monocytes then cultured ex vivo to obtain immature dendritic cells (DC). The treatment targets single lymphoma nodes with radiation (single fraction of 8 Gy), ultrasound-guided injections of autologous DCs , low-dose rituximab (5 mg) and GM-CSF sc. This sequential intranodal immunotherapy (SIIT) is repeated three times, targeting different lymphoma nodes. Anti-PD1 monoclonal antibody (Pembrolizumab) is given iv at each cycle of SIIT and then every third week for a total of 11 cycles. Patients are evaluated for clinical response with PET/CT, CT and bone marrow analysis. CD8 and CD4 T cell responses against autologous tumor cells are measured in blood after treatment by flow cytometry. The primary aims are to induce systemic clinical responses and correlated T cell responses which may prolong time to next standard therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Radiotherapy 8 Gy single dose
Intranodal injection 5 mg
Intranodal injection of 1 x 10 e8 cells
Subcutaneous injection of 50 ug
Intravenous infusion of 200 mg
Oslo University Hospital Radiumhospitalet
Oslo, Norway
Overall response rate
Change in tumor load from baseline until maximal regression
Time frame: Evaluated at baseline, 2, 4, 8, 12 and 24 months
Duration of response
DOR
Time frame: From date of documented response until progression, assessed up to 60 months
Progression-free survival
PFS
Time frame: From date of inclusion until date of documented progression or death of any cause, whichever came first, assessed up to 60 months
Time to next treatment
TNT
Time frame: From date of inclusion until start of next treatment, assessed up to 60 months
Overall survival
OS
Time frame: From date of inclusion until death of any cause, assessed up to 60 months
Change in total tumor volume
cTTV
Time frame: Compared assessments at inclusion and at time of best response, as assessed up to 60 months, an average of 12 months
Safety: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: From inclusion, assessed up to 60 months
Anti-tumor T cell responses in blood
T-cell proliferation
Time frame: Assessed at inclusion and up to 60 months
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