Dual Vaccine Trial in Myeloproliferative Neoplasms

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: Polycythemia Vera; Essential Thrombocythemia
• Intervention / Treatment: Drug: PD-L1 peptide: PD-L1 Long(19-27) Peptide sequence: FMTYWHLLNAFTVTVPKDL; Drug: Arginase1 peptide: ArgLong2(169-206) Peptide sequence ISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRL

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Eligibility Criteria

• Ages Eligible for Study: 16 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

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: 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	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	Adverse events are graded 1-5 according to the criteria	1 year
Clinical response	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

• Sponsor: Inge Marie Svane
• Investigators: Principal Investigator: Jacob H Grauslund, MD, CENTER FOR CANCER IMMUNE THERAPY, CCIT-DK

Study record dates

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: Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms; Thrombocytosis; Thrombocythemia, Essential; Myeloproliferative Disorders; Polycythemia Vera; Polycythemia
• 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