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Vaccination With PD-L1 Peptide Against Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 1

Locations

Denmark

Study Type

Interventional

Intervention

PD-L1 peptide vaccine

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring myeloma, vaccination, PD-L1, peptide vaccine, cancer vaccine, immunotherapy

Eligibility Criteria

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

Inclusion Criteria:

Histologically verified multiple myeloma
Newly treated with HDT and no signs of relapse
Age ≥18 years
Performance status ≤ 2 (ECOG-scale)
Expected survival > 3 months
Sufficiently regenerated bone marrow function, i.e.
1. Leucocytes ≥ 1,5 x 109
2. Granulocytes ≥ 1,0 x 109
3. Thrombocytes ≥ 20 x 109
Creatinine < 2.5 upper normal limit, i.e. < 300 μmol/l
Sufficient liver function, i.e.
1. ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/l
2. Bilirubin < 30 U/l
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:

Non-secretory myeloma
Other malignancies in the medical history excluding squamous cell carcinoma of the skin and patients cured for another malignant disease with no sign of relapse three years after ended treatment.
Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus.
Acute or chronic viral infection e.g. HIV, hepatitis or tuberculosis
Serious known allergies or earlier anaphylactic reactions.
Known sensibility towards Montanide ISA-51
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%
Patients taking immune suppressive medications incl. corticosteroids and methotrexate at the time of enrollment
Psychiatric disorders that per investigator judgment could influence compliance.
Treatment with other experimental drugs
Treatment with other anti-cancer drugs - except bisphosphonates and denosumab
Patients with active uncontrolled hypercalcemia
Patients who have received chemotherapy, immune therapy, radiation therapy within the last 28 days.

Sites / Locations

Department of Hematology, Universityhospital Herlev and Gentofte

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vaccination

Arm Description

Vaccine: PD-L1 peptide.

Outcomes

Primary Outcome Measures

Incidence of toxicity

CTCAE = Common Terminology Criteria for Adverse Events v. 4.0 will be used for registration of toxicity

Secondary Outcome Measures

Evaluation of immunological responses

Immunological assays will be used to identify immunological responses.

Full Information

NCT ID

NCT03042793

First Posted

February 2, 2017

Last Updated

July 2, 2020

Sponsor

Lene Meldgaard Knudsen

1. Study Identification

Unique Protocol Identification Number

NCT03042793

Brief Title

Vaccination With PD-L1 Peptide Against Multiple Myeloma

Official Title

Vaccination With PD-L1 Peptide With Montanide Against Multiple Myeloma After High Dose Chemotherapy With Stem Cell Support. A Phase I First-in-human Study.

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

February 1, 2017 (Actual)

Primary Completion Date

May 14, 2020 (Actual)

Study Completion Date

May 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Lene Meldgaard Knudsen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Title: Vaccination with PD-L1 peptide with Montanide against multiple myeloma after high dose chemotherapy with stem cell support. A phase I first-in-human study. Hypothesis: In this trial the investigators assess a new immunotherapeutic strategy targeting the immune checkpoint molecule PD-L1 to investigate the potential of vaccination against PD-L1 as a possible anticancer target.

Detailed Description

Background: Multiple myeloma is the second most common hematologic cancer which is despite advances in treatment is still incurable for most patients. In this trial the investigators assess a new immunotherapeutic strategy targeting the immune checkpoint molecule PD-L1 to investigate the potential of vaccination against PD-L1 as a possible anticancer target. PD-L1 has been recognized as an important factor in immune regulation and development of immune tolerance in the microenvironment of cancer cells. Cells that express PD-L1 on their surface are known to inhibit the immune system. As seen with the recent advances in immunotherapy against cancer with antibodies against PD-L1, the the immunosuppressive role of the molecule PD-L1 can be antagonized to the benefit of patients with cancer. PD-L1 is expressed on both cancer cells, antigen presenting cells and immunosuppressive cells in the tumor micro-environment. Vaccination against PD-L1 is therefore two sided. The investigators aim to stimulate PD-L1 specific T-cells, hence eliminating both PD-L1 positive tumor cells as well as PD-L1 positive immunosuppressive and antigen presenting cells in the tumor microenvironment. The primary endpoints are safety and toxicity evaluation. Secondary endpoint is immunological response. Clinical response will be described.

6. Conditions and Keywords

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

Multiple Myeloma

Keywords

myeloma, vaccination, PD-L1, peptide vaccine, cancer vaccine, immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vaccination

Arm Type

Experimental

Arm Description

Vaccine: PD-L1 peptide.

Intervention Type

Biological

Intervention Name(s)

PD-L1 peptide vaccine

Intervention Description

PD-L1 peptide given subcutaneously with Montanide ISA-51

Primary Outcome Measure Information:

Title

Incidence of toxicity

Description

CTCAE = Common Terminology Criteria for Adverse Events v. 4.0 will be used for registration of toxicity

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Evaluation of immunological responses

Description

Immunological assays will be used to identify immunological responses.

Time Frame

12 months

Other Pre-specified Outcome Measures:

Title

Clinical response

Description

Will be described according to standard IMWG-criteria for multiple myeloma.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically verified multiple myeloma Newly treated with HDT and no signs of relapse Age ≥18 years Performance status ≤ 2 (ECOG-scale) Expected survival > 3 months Sufficiently regenerated bone marrow function, i.e. Leucocytes ≥ 1,5 x 109 Granulocytes ≥ 1,0 x 109 Thrombocytes ≥ 20 x 109 Creatinine < 2.5 upper normal limit, i.e. < 300 μmol/l Sufficient liver function, i.e. ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/l Bilirubin < 30 U/l 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: Non-secretory myeloma Other malignancies in the medical history excluding squamous cell carcinoma of the skin and patients cured for another malignant disease with no sign of relapse three years after ended treatment. Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus. Acute or chronic viral infection e.g. HIV, hepatitis or tuberculosis Serious known allergies or earlier anaphylactic reactions. Known sensibility towards Montanide ISA-51 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% Patients taking immune suppressive medications incl. corticosteroids and methotrexate at the time of enrollment Psychiatric disorders that per investigator judgment could influence compliance. Treatment with other experimental drugs Treatment with other anti-cancer drugs - except bisphosphonates and denosumab Patients with active uncontrolled hypercalcemia Patients who have received chemotherapy, immune therapy, radiation therapy within the last 28 days.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicolai Jørgensen, MD

Organizational Affiliation

Center for Cancer Immune Therapy, Universityhospital Herlev and Gentofte

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Hematology, Universityhospital Herlev and Gentofte

City

Herlev

ZIP/Postal Code

2730

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

33240282

Citation

Jorgensen NG, Klausen U, Grauslund JH, Helleberg C, Aagaard TG, Do TH, Ahmad SM, Olsen LR, Klausen TW, Breinholt MF, Hansen M, Martinenaite E, Met O, Svane IM, Knudsen LM, Andersen MH. Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial. Front Immunol. 2020 Nov 9;11:595035. doi: 10.3389/fimmu.2020.595035. eCollection 2020.

Results Reference

derived

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Vaccination With PD-L1 Peptide Against Multiple Myeloma

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