Clinical trial NCT03939234: Peptide Vaccination With PD-L1 and PD-L2 Peptides in Untreated Chronic Lymphatic Leukemia.
Official title: Peptide Vaccination With PD-L1 and PD-L2 Peptides in Untreated Chronic Lymphatic Leukemia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: IO Biotech
First posted: 2019-05-06
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is investigating the efficacy of PD-L1 and PD-L2 peptides in untreated CLL patients with unmutated IGHV gene status.

Detailed description: Chronic lymphocytic leukemia (CLL) is an incurable disease with the unmutated immunoglobulin heavy chain variable region (IGHV) gene status being an unfavorable prognostic marker. These patients have shorter time to first treatment which consist of toxic chemotherapy.

Programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) are immune checkpoints hampering immune responses in many tumors including CLL. These proteins are expressed by suppressive bystander cells as well as CLL cells. Vaccinating subcutaneously with PD-L1 and PD-L2 peptides mobilises cytoxic T-cells specific towards PD-L1 and PD-L2 expressing cells. In this study we investigate if the PD-L1 and PD-L2 specific responses can overcome leukemic cells in CLL.

Eligibility criteria: Inclusion Criteria:

* CLL according to national guidelines (Lymphoma.dk).
* Unmutated IGHV gene according to ERIC recommendations.(25)
* No prior CLL directed treatment
* Age ≥ 18
* Eastern cooperative oncology group (ECOG) performance status of 0 or 1
* No life-threatening conditions
* Adequate bone marrow function: Neutrophils \> 1,0 x 109/l; Platelets \> 100 x 109/l
* Adequate renal function: Glomeruli filtration rate (eGFR)/1,73 m2 \> 50 mL/min
* Adequate liver function: Aspartate Aminotransferase \< 100 U/L
* For fertile women: agreement to use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 120 days after the last treatment.
* For men: agreement to use contraceptive measures and agreement to refrain from donating sperm.

Exclusion Criteria:

* Other active malignant diseases requiring treatment.
* Significant medical condition per investigators judgement e.g. severe Asthma or chronic obstructive lung disease (COLD), poorly regulated heart condition, insulin dependent diabetes mellitus.
* Acute or chronic viral/bacterial infection e.g. human immunodeficiency virus (HIV), Cytomegalo virus (CMV), Epstein-barr virus (EBV), hepatitis or tuberculosis
* Serious known allergies or earlier anaphylactic reactions.
* Known sensibility towards Montanide ISA51
* 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.
* Pregnant and breastfeeding women.
* Fertile women not using secure contraception with a failure rate less than \< 1%
* Psychiatric disorders that according to the investigator could influence compliance.
* Treatment with other experimental drugs

Primary outcomes:
measure: Clinical response according to IW-CLL
timeFrame: 1 year
Secondary outcomes:
measure: Immune response by elispot
timeFrame: 1 year
measure: Grades of adverse events (AE)
timeFrame: 1 year
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Herlev Hospital
Study officials:
affiliation: Herlev Hospital
name: Uffe M Klausen, MD
role: PRINCIPAL_INVESTIGATOR
References: