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

Follicular Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03381768
• Other study ID #: FL1701
• Secondary ID: 2017-002000-28
• Status: Completed
• Phase: Phase 1
• Start date: December 12, 2017
• Est. completion date: February 12, 2020

Study information

• Verified date: February 2021
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: February 12, 2020
• Est. primary completion date: February 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• PD-L2 peptide
100 ug PD-L2 peptide dissolved in DMSO and water mixed with 500ul montanide.
• 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.

Locations

Country	Name	City	State
Denmark	Herlev Hospital	Herlev	RegionH

Sponsors (1)

Lead Sponsor	Collaborator
Lars Møller Pedersen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical response according to Lugano criteria	Changes in tumor size on CT	1 year
Other	Clinical response according to Lugano criteria	Changes in tumor metabolism on PET	1 year
Other	Minimal residual disease	measured by circulating tumor DNA	1 year
Primary	Adverse events evaluated by CTCAE 4.03	Adverse events are graded 1-5 according to the criteria	1 year follow up
Secondary	Immune responses	T-cell cytokine release towards target antigens	1 year