Peptide Vaccination Against PD-L1 and PD-L2 in Relapsed Follicular Lymphoma

Study Overview
=================
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.

Official Title
-----------------
PD-L1 and PD-L2 Peptide Vaccination as Consolidation for Relapsed Follicular Lymphoma

Conditions
-----------------
Follicular Lymphoma

Intervention / Treatment
-----------------
* Biological: PD-L2 peptide
* Biological: PD-L2 and PD-L1 peptide


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Fixed dose safety study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>3 vaccines of PD-L2 peptide followed by 12 vaccines of PD-L2 and PD-L1 peptide, over the course of one year. | Biological: PD-L2 peptide<br>* 100 ug PD-L2 peptide dissolved in DMSO and water mixed with 500ul montanide.<br>Biological: PD-L2 and PD-L1 peptide<br>* 100 ug PD-L2 peptide and 100ug PD-L1 peptide dissolved in DMSO and water mixed with 500ul montanide.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events evaluated by CTCAE 4.03 | Adverse events are graded 1-5 according to the criteria | 1 year follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune responses | T-cell cytokine release towards target antigens | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PD-L1, PD-L2, peptide vaccine