Peptide Vaccination With PD-L1 and PD-L2 Peptides in Untreated Chronic Lymphatic Leukemia.

Lars Møller Pedersen

Status and phase: Completed; Phase 2

Conditions: Chronic Lymphocytic Leukemia

Treatments: Combination Product: PD-L1, PD-L2 peptides with Montanide ISA51

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03939234

CLL19H1

2018-004869-14 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Vaccination

Experimental group

Description:

Untreated CLL patients with unmutated IgHV gene with a cut of at maximum of 2 % mutations. According to guidelines from the European Research Initiative on CLL (ERIC).

Treatment:

Combination Product: PD-L1, PD-L2 peptides with Montanide ISA51