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出境医 / 临床实验 / Peptide Vaccination With IO103 and IO120 in Patients With Chronic Lymphocytic Leukemia.

Peptide Vaccination With IO103 and IO120 in Patients With Chronic Lymphocytic Leukemia.

Study Description
Brief Summary:
This study is investigating the efficacy of PD-L1(IO103) and PD-L2(IO120) peptides in untreated CLL patients with unmutated IGHV gene status.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Combination Product: PD-L1, PD-L2 peptides with Montanide ISA51 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Peptide Vaccination With PD-L1(IO103) and PD-L2(IO120) Peptides in Untreated Chronic Lymphatic Leukemia.
Actual Study Start Date : April 26, 2019
Estimated Primary Completion Date : March 15, 2021
Estimated Study Completion Date : March 15, 2021
Arms and Interventions
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 Name: IO103, IO120
Outcome Measures
Primary Outcome Measures :
  1. Clinical response according to IW-CLL [ Time Frame: 1 year ]
    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 :
  1. Immune response by elispot [ Time Frame: 1 year ]
    T-cell responses measured by Enzyme-linked immunospot assay (ELISpot) counting the number of spots with cytokine release.

  2. Grades of adverse events (AE) [ Time Frame: 1 year ]
    Registered according to common terminology criteria for adverse events (CTCAE) v4.03. Each AE will be Graded I-V.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Locations
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Denmark
Herlev Hospital
Herlev, Denmark, 2730
Sponsors and Collaborators
Lars Møller Pedersen
IO Biotech
Investigators
Layout table for investigator information
Principal Investigator: Uffe M Klausen, MD Herlev Hospital
Tracking Information
First Submitted Date  ICMJE May 3, 2019
First Posted Date  ICMJE May 6, 2019
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE April 26, 2019
Estimated Primary Completion Date March 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2019) 		Clinical response according to IW-CLL [ Time Frame: 1 year ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: May 3, 2019) 		Clinical response [ Time Frame: 1 year ]
Changes in circulating lymphocytes and lymphnode/spleen/liver size according to criteria from the international working group on CLL (IW-CLL)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2019)
  • Immune response by elispot [ Time Frame: 1 year ]
    T-cell responses measured by Enzyme-linked immunospot assay (ELISpot) counting the number of spots with cytokine release.
  • Grades of adverse events (AE) [ Time Frame: 1 year ]
    Registered according to common terminology criteria for adverse events (CTCAE) v4.03. Each AE will be Graded I-V.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
  • Immune response [ Time Frame: 1 year ]
    T-cell responses measured by Enzyme-linked immunospot assay (ELISpot) with tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) release.
  • Adverse Events [ Time Frame: 1 year ]
    Registered according to common terminology criteria for adverse events (CTCAE) v4.03
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Peptide Vaccination With IO103 and IO120 in Patients With Chronic Lymphocytic Leukemia.
Official Title  ICMJE Peptide Vaccination With PD-L1(IO103) and PD-L2(IO120) Peptides in Untreated Chronic Lymphatic Leukemia.
Brief Summary This study is investigating the efficacy of PD-L1(IO103) and PD-L2(IO120) 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE 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 Name: IO103, IO120
Study Arms  ICMJE 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).
Intervention: Combination Product: PD-L1, PD-L2 peptides with Montanide ISA51
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2019) 		20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 15, 2021
Estimated Primary Completion Date March 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03939234
Other Study ID Numbers  ICMJE CLL19H1
2018-004869-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lars Møller Pedersen, Herlev Hospital
Study Sponsor  ICMJE Lars Møller Pedersen
Collaborators  ICMJE IO Biotech
Investigators  ICMJE
Principal Investigator: Uffe M Klausen, MD Herlev Hospital
PRS Account Herlev Hospital
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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