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

NCT ID: NCT03939234

Last Updated: 2022-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-26
• Study Completion Date: 2021-03-15

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vaccination

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).

Group Type: EXPERIMENTAL

PD-L1, PD-L2 peptides with Montanide ISA51

Intervention Type: COMBINATION_PRODUCT

PD-L1: 19 amino acid sequence from the PD-L1 protein; PD-L2: 21 amino acid sequence from the PD-L2 protein; The peptides are dissolved in dimethyl sulphoxide (DMSO) and mixed with Montanide.

Interventions

PD-L1, PD-L2 peptides with Montanide ISA51

PD-L1: 19 amino acid sequence from the PD-L1 protein; PD-L2: 21 amino acid sequence from the PD-L2 protein; The peptides are dissolved in dimethyl sulphoxide (DMSO) and mixed with Montanide.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

IO103, IO120

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IO Biotech

INDUSTRY

Sponsor Role: collaborator

Lars Møller Pedersen

OTHER

Sponsor Role: lead

Responsible Party

Lars Møller Pedersen

Chief Phycisian

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Uffe M Klausen, MD

Role: PRINCIPAL_INVESTIGATOR

Herlev Hospital

Locations

Herlev Hospital

Herlev, , Denmark

Countries

Denmark

References

Klausen U, Grauslund JH, Jorgensen NGD, Ahmad SM, Jonassen M, Weis-Banke SE, Martinenaite E, Pedersen LB, Lisle TL, Gang AO, Enggaard L, Hansen M, Holmstrom MO, Met O, Svane IM, Niemann CU, Pedersen LM, Andersen MH. Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV. Front Oncol. 2022 Nov 22;12:1023015. doi: 10.3389/fonc.2022.1023015. eCollection 2022.

Reference Type: DERIVED

PMID: 36483037 (View on PubMed)

Other Identifiers

2018-004869-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLL19H1

Identifier Type: -

Identifier Source: org_study_id