Vaccination With PD-L1 Peptide Against Multiple Myeloma

NCT ID: NCT03042793

Last Updated: 2020-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-01
• Study Completion Date: 2020-05-14

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.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Vaccination

Vaccine: PD-L1 peptide.

Group Type: EXPERIMENTAL

PD-L1 peptide vaccine

Intervention Type: BIOLOGICAL

PD-L1 peptide given subcutaneously with Montanide ISA-51

Interventions

PD-L1 peptide vaccine

PD-L1 peptide given subcutaneously with Montanide ISA-51

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Histologically verified multiple myeloma

2. Newly treated with HDT and no signs of relapse

3. Age ≥18 years

4. Performance status ≤ 2 (ECOG-scale)

5. Expected survival > 3 months

6. Sufficiently regenerated bone marrow function, i.e.

1. Leucocytes ≥ 1,5 x 109

2. Granulocytes ≥ 1,0 x 109

3. Thrombocytes ≥ 20 x 109

7. Creatinine < 2.5 upper normal limit, i.e. < 300 μmol/l

8. Sufficient liver function, i.e.

1. ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/l

2. Bilirubin < 30 U/l

9. 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.

10. For men: agreement to use contraceptive measures and agreement to refrain from donating sperm.

Exclusion Criteria

1. Non-secretory myeloma

2. 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.

3. Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus.

4. Acute or chronic viral infection e.g. HIV, hepatitis or tuberculosis

5. Serious known allergies or earlier anaphylactic reactions.

6. Known sensibility towards Montanide ISA-51

7. 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.

8. Pregnant and breastfeeding women.

9. Fertile women not using secure contraception with a failure rate less than < 1%

10. Patients taking immune suppressive medications incl. corticosteroids and methotrexate at the time of enrollment

11. Psychiatric disorders that per investigator judgment could influence compliance.

12. Treatment with other experimental drugs

13. Treatment with other anti-cancer drugs - except bisphosphonates and denosumab

14. Patients with active uncontrolled hypercalcemia

15. Patients who have received chemotherapy, immune therapy, radiation therapy within the last 28 days.

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

Sponsors

Lene Meldgaard Knudsen

OTHER

Sponsor Role: lead

Responsible Party

Lene Meldgaard Knudsen

MD, DMSc, Head of Department, Department of Haematology, Universityhospital Herlev and Gentofte

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nicolai Jørgensen, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Cancer Immune Therapy, Universityhospital Herlev and Gentofte

Locations

Department of Hematology, Universityhospital Herlev and Gentofte

Herlev, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 33240282 (View on PubMed)

Other Identifiers

2016-000990-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MY0001

Identifier Type: -

Identifier Source: org_study_id