Dual Vaccine Trial in Myeloproliferative Neoplasms

July 12, 2023 updated by: Inge Marie Svane
A phase I-II study in patients with mutated MPN by vaccinating with PD-L1 and Aginase1 peptides with Montanide ISA-51 as adjuvant, to monitor the immunological response to vaccination and subsequently safety, toxicity and clinical effect.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Herlev, Denmark, 2730
        • National Center for Cancer Immune Therapy (CCIT-DK)
    • Capital Region
      • Herlev, Capital Region, Denmark, 2730
        • Herlev Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Diagnosis of essential thrombocythemia or Polycythemia Vera, according to the WHO criteria123,124 2. Age ≥18 years 3. Performance status ≤ 2 (ECOG-scale) 4. Expected survival > 3 months 5. Sufficient bone marrow function 6. Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l 7. Sufficient liver function, i.e.

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

    2. Bilirubin < 30 U/l 8. For 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.

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

      Exclusion criteria

      1. Other malignancies in the medical history excluding basal cell carcinoma. Patients cured for another malignant disease with no sign of relapse five years after ended treatment is allowed to enter the protocol.
      2. Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus.
      3. Acute or chronic viral or bacterial infection e.g. HIV, hepatitis or tuberculosis
      4. Serious known allergies or earlier anaphylactic reactions.
      5. Known sensibility to Montanide ISA-51
      6. 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.
      7. Pregnant and breastfeeding women.
      8. Fertile women not using secure contraception with a failure rate less than < 1%
      9. Patients taking immune suppressive medications incl. systemic corticosteroids and methotrexate at the time of enrollment
      10. Psychiatric disorders that per investigator judgment could influence compliance.
      11. Treatment with other experimental drugs
      12. Treatment with other anti-cancer drugs - except IFN-a, hydroxyurea or anagrelide.
      13. Treatment with ruxolitinib.
      14. Treatment with chemotherapy or immune therapy (excluding IFN-a, hydroxyurea or anagrelide) within the last 28 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: intervention

Vaccination with:

PD-L1 peptide:

PD-L1 Long(19-27) Peptide sequence: FMTYWHLLNAFTVTVPKDL Dose: 100 µg PD-L1 long1 dissolved in DMSO/water - Total volume: 0,5 ml.

Arginase1 peptide:

ArgLong2(169-206) Peptide sequence ISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRL Dose: 200 µg ARGLong2 dissolved in DMSO/water - Total volume: 0,5 ml.

Both vaccines are given at a treatment. Adjuvant Montanide ISA 51 0,5ml is mixed with the peptides before treatment To be administered every second week - a total of twelve times, with a possibility of additional six treatments.
Drug: PD-L1 peptide: PD-L1 Long(19-27) Peptide sequence: FMTYWHLLNAFTVTVPKDL
Peptide vaccination
Other Names:
  • PD-L1Long
Drug: Arginase1 peptide: ArgLong2(169-206) Peptide sequence ISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRL
Peptide vaccination
Other Names:
  • ARGLong2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune response
Time Frame: 1 year
T-cell cytokine release towards target antigens
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events evaluated by CTCAE v. 5.0
Time Frame: 1 year
Adverse events are graded 1-5 according to the criteria
1 year
Clinical response
Time Frame: 10 year
Vaccinations will induce clinical response in 2 patients, either partial response or better, according response criteria for PV and ET or clinical response as a reduction of mutated allelic burden - 10% from baseline at any time.
10 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inge Marie Svane

Investigators

  • Principal Investigator: Jacob H Grauslund, MD, CENTER FOR CANCER IMMUNE THERAPY, CCIT-DK

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2019

Primary Completion (Actual)

July 10, 2022

Study Completion (Actual)

July 10, 2022

Study Registration Dates

First Submitted

July 11, 2019

First Submitted That Met QC Criteria

August 7, 2019

First Posted (Actual)

August 9, 2019

Study Record Updates

Last Update Posted (Actual)

July 13, 2023

Last Update Submitted That Met QC Criteria

July 12, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MPN19H2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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