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

Lars Møller Pedersen

Status and phase: Completed; Phase 1

Conditions: Follicular Lymphoma

Treatments: Biological: PD-L2 peptide; Biological: PD-L2 and PD-L1 peptide

Study type: Interventional

Funder types: Other

Identifiers

NCT03381768

FL1701

2017-002000-28 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

8 participants in 1 patient group

Study group

Experimental group

Description:

3 vaccines of PD-L2 peptide followed by 12 vaccines of PD-L2 and PD-L1 peptide, over the course of one year.

Treatment:

Biological: PD-L2 and PD-L1 peptide

Biological: PD-L2 peptide