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

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

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Combination product: PD-L1, PD-L2 peptides with Montanide ISA51

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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).	Combination product: 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.; Other Names: IO103, IO120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response according to IW-CLL	Progressive disease (PD), stable disease (SD), partial response (PR), complete response (CR) calculated on basis of changes in circulating lymphocytes and lymphnode/spleen/liver size according to criteria from the international working group on CLL (IW-CLL).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response by elispot	T-cell responses measured by Enzyme-linked immunospot assay (ELISpot) counting the number of spots with cytokine release.	1 year
Grades of adverse events (AE)	Registered according to common terminology criteria for adverse events (CTCAE) v4.03. Each AE will be Graded I-V.	1 year

Collaborators and Investigators

• Sponsor: Lars Møller Pedersen
• Collaborators: IO Biotech
• Investigators: Principal Investigator: Uffe M Klausen, MD, Herlev Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 26, 2019
• Primary Completion (ACTUAL): March 15, 2021
• Study Completion (ACTUAL): March 15, 2021

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: May 3, 2019
• First Posted (ACTUAL): May 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Monatide (IMS 3015)
• Other Study ID Numbers: CLL19H1; 2018-004869-14 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No