Clinical trial NCT03042793: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: myeloma
vaccination
PD-L1
peptide vaccine
cancer vaccine
immunotherapy
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2017-02-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of toxicity
timeFrame: 12 months
Secondary outcomes:
measure: Evaluation of immunological responses
timeFrame: 12 months
Other outcomes:
measure: Clinical response
timeFrame: 12 months
Locations:
city: Herlev
country: Denmark
facility: Department of Hematology, Universityhospital Herlev and Gentofte
Study officials:
affiliation: Center for Cancer Immune Therapy, Universityhospital Herlev and Gentofte
name: Nicolai Jørgensen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.