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

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

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.

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Biological: PD-L2 peptide; Biological: PD-L2 and PD-L1 peptide

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • RegionH
    • Herlev, RegionH, Denmark, 2730
      • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; 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; 100 ug PD-L2 peptide dissolved in DMSO and water mixed with 500ul montanide.; Biological: PD-L2 and PD-L1 peptide; 100 ug PD-L2 peptide and 100ug PD-L1 peptide dissolved in DMSO and water mixed with 500ul montanide.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response according to Lugano criteria	Changes in tumor size on CT	1 year
Clinical response according to Lugano criteria	Changes in tumor metabolism on PET	1 year
Minimal residual disease	measured by circulating tumor DNA	1 year

Collaborators and Investigators

• Sponsor: Lars Møller Pedersen
• Investigators: Principal Investigator: Uffe Klausen, MD, Hematological department, Herlev Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2017
• Primary Completion (Actual): February 12, 2020
• Study Completion (Actual): February 12, 2020

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 22, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: PD-L1; peptide vaccine; PD-L2
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular
• Other Study ID Numbers: FL1701; 2017-002000-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No