Vaccination With PD-L1 Peptide Against Multiple Myeloma

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.

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: PD-L1 peptide vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Department of Hematology, Universityhospital Herlev and Gentofte

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccination; Vaccine: PD-L1 peptide.	Biological: PD-L1 peptide vaccine; PD-L1 peptide given subcutaneously with Montanide ISA-51

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of toxicity	CTCAE = Common Terminology Criteria for Adverse Events v. 4.0 will be used for registration of toxicity	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of immunological responses	Immunological assays will be used to identify immunological responses.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Will be described according to standard IMWG-criteria for multiple myeloma.	12 months

Collaborators and Investigators

• Sponsor: Lene Meldgaard Knudsen
• Investigators: Principal Investigator: Nicolai Jørgensen, MD, Center for Cancer Immune Therapy, Universityhospital Herlev and Gentofte

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): May 14, 2020
• Study Completion (Actual): May 14, 2020

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 3, 2017

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: immunotherapy; PD-L1; vaccination; cancer vaccine; peptide vaccine; myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: MY0001; 2016-000990-19 (EudraCT Number)

Drug and device information, study documents

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