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

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
PD-L1, PD-L2 peptides with Montanide ISA51
Sponsored by
Lars Møller Pedersen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Herlev Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vaccination

Arm 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).

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Full Information

First Posted
May 3, 2019
Last Updated
February 4, 2022
Sponsor
Lars Møller Pedersen
Collaborators
IO Biotech
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1. Study Identification

Unique Protocol Identification Number
NCT03939234
Brief Title
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

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
April 26, 2019 (Actual)
Primary Completion Date
March 15, 2021 (Actual)
Study Completion Date
March 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Lars Møller Pedersen
Collaborators
IO Biotech

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vaccination
Arm Type
Experimental
Arm 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).
Intervention Type
Combination Product
Intervention Name(s)
PD-L1, PD-L2 peptides with Montanide ISA51
Other Intervention Name(s)
IO103, IO120
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical response according to IW-CLL
Description
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).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Immune response by elispot
Description
T-cell responses measured by Enzyme-linked immunospot assay (ELISpot) counting the number of spots with cytokine release.
Time Frame
1 year
Title
Grades of adverse events (AE)
Description
Registered according to common terminology criteria for adverse events (CTCAE) v4.03. Each AE will be Graded I-V.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Uffe M Klausen, MD
Organizational Affiliation
Herlev Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Herlev Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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