Vaccination With PD-L1 Peptide Against Multiple Myeloma

Multiple Myeloma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03042793
• Other study ID #: MY0001
• Secondary ID: 2016-000990-19
• Status: Completed
• Phase: Phase 1
• Start date: February 1, 2017
• Est. completion date: May 14, 2020

Study information

• Verified date: July 2020
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 14, 2020
• Est. primary completion date: May 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• PD-L1 peptide vaccine
PD-L1 peptide given subcutaneously with Montanide ISA-51

Locations

Country	Name	City	State
Denmark	Department of Hematology, Universityhospital Herlev and Gentofte	Herlev

Sponsors (1)

Lead Sponsor	Collaborator
Lene Meldgaard Knudsen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical response	Will be described according to standard IMWG-criteria for multiple myeloma.	12 months
Primary	Incidence of toxicity	CTCAE = Common Terminology Criteria for Adverse Events v. 4.0 will be used for registration of toxicity	12 months
Secondary	Evaluation of immunological responses	Immunological assays will be used to identify immunological responses.	12 months