Clinical trial NCT03381768: Peptide Vaccination Against PD-L1 and PD-L2 in Relapsed Follicular Lymphoma
Official title: PD-L1 and PD-L2 Peptide Vaccination as Consolidation for Relapsed Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Follicular Lymphoma
Keywords: PD-L1
PD-L2
peptide vaccine
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2017-12-22
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Fixed dose safety study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adverse events evaluated by CTCAE 4.03
timeFrame: 1 year follow up
Secondary outcomes:
measure: Immune responses
timeFrame: 1 year
Other outcomes:
measure: Clinical response according to Lugano criteria
timeFrame: 1 year
measure: Clinical response according to Lugano criteria
timeFrame: 1 year
measure: Minimal residual disease
timeFrame: 1 year
Locations:
city: Herlev
country: Denmark
facility: Herlev Hospital
state: RegionH
Study officials:
affiliation: Hematological department, Herlev Hospital
name: Uffe Klausen, MD
role: PRINCIPAL_INVESTIGATOR
References: