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

Phase 1

Completed

• Conditions: Follicular Lymphoma
• Interventions: Biological: PD-L2 peptide; Biological: PD-L2 and PD-L1 peptide

• Registration Number: NCT03381768
• Lead Sponsor: Lars Møller Pedersen

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.

Study Timeline

• Study First Submitted: 2017-12-08
• Study Start: 2017-12-12
• Study First Submitted QC: 2017-12-18
• Study First Posted: 2017-12-22
• Primary Completion: 2020-02-12
• Study Completion: 2020-02-12
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-23
• Last Update Posted: 2021-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study group	PD-L2 peptide	3 vaccines of PD-L2 peptide followed by 12 vaccines of PD-L2 and PD-L1 peptide, over the course of one year.
Study group	PD-L2 and PD-L1 peptide	3 vaccines of PD-L2 peptide followed by 12 vaccines of PD-L2 and PD-L1 peptide, over the course of one year.

Primary Outcome Measures

Name	Time	Method
Adverse events evaluated by CTCAE 4.03	1 year follow up	Adverse events are graded 1-5 according to the criteria

Secondary Outcome Measures

Name	Time	Method
Immune responses	1 year	T-cell cytokine release towards target antigens

Trial Locations

Locations (1)

Herlev Hospital; 🇩🇰 Herlev, RegionH, Denmark