Follicular Lymphoma
Conditions
Keywords
PD-L1, PD-L2, peptide vaccine
Brief summary
An open phase-1, first-in-human, clinical trial investigating the safety and immunological effects of peptide vaccination with Programmed Death Ligand 1 and 2 (PD-L1 and PD-L2) peptides in patients with relapsed follicular lymphoma.
Detailed description
Follicular lymphoma (FL) is the the most common of the indolent lymphomas, with an incidence in Denmark of 220 per year. In 90% of the cases the disease is incurable why the treatment strategy often is watchful waiting until significant signs of progression or transformation. After chemotherapy, maintenance therapy is often used to increase disease control. The microenvironment and immune escape mechanism are believed to play a major role in the persistence of the lymphoma. One escape mechanism is the PD-L1 and PD-L2 molecules expressed in the microenvironment of follicular lymphoma inhibiting the T-cells. By stimulating the T-cells to attack PD-L1 and PD-L2 expressing cells we hope to hamper the immunosuppressive tumor environment and establish immune tumor control. 10 patients treated with standard therapy are needed for the trial and each patient will receive 15 vaccinations over the course of one year.
Interventions
BIOLOGICALPD-L2 peptide
100 ug PD-L2 peptide dissolved in DMSO and water mixed with 500ul montanide.
BIOLOGICALPD-L2 and PD-L1 peptide
100 ug PD-L2 peptide and 100ug PD-L1 peptide dissolved in DMSO and water mixed with 500ul montanide.
Sponsors
Lars Møller Pedersen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Fixed dose safety study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented FL grade I-IIIa, with no sign of current transformation. Patients cured of transformed lymphoma are eligible. * A minimum of one line of induction therapy. Maintenance rituximab can continue along with the vaccination * At least partial response to the latest standard treatment * A minimum of 4 weeks since last treatment * Age ≥ 18 * ECOG performance status of 0 or 1 * Life expectancy ≥ 12 weeks * Adequate hematologic and end-organ function
Exclusion criteria
* Progression with the presence of at least one GELF criteria or transformation at inklusion time. * Other active malignant diseases * Significant medical condition per investigators judgement e.g. severe Asthma/COLD, poorly regulated heart condition, insulin dependent diabetes mellitus. * Acute or chronic viral/bacterial infection e.g. HIV, CMV, EBV, hepatitis or tuberculosis * Serious known allergies or earlier anaphylactic reactions. * Known sensibility towards Montanide ISA-51 * Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events evaluated by CTCAE 4.03 | 1 year follow up | Adverse events are graded 1-5 according to the criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune responses | 1 year | T-cell cytokine release towards target antigens |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clinical response according to Lugano criteria | 1 year | Changes in tumor size on CT |
| Minimal residual disease | 1 year | measured by circulating tumor DNA |
Countries
Denmark
Outcome results
None listed