Dual Vaccine Trial in Myeloproliferative Neoplasms

Inge Marie Svane

Status and phase: Completed; Phase 2; Phase 1

Conditions: Polycythemia Vera; Essential Thrombocythemia

Treatments: Drug: PD-L1 peptide: PD-L1 Long(19-27) Peptide sequence: FMTYWHLLNAFTVTVPKDL; Drug: Arginase1 peptide: ArgLong2(169-206) Peptide sequence ISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRL

Study type: Interventional

Funder types: Other

Identifiers

NCT04051307

MPN19H2

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

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

  3. 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

intervention

Experimental group

Description:

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.

Treatment:

Drug: Arginase1 peptide: ArgLong2(169-206) Peptide sequence ISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRL

Drug: PD-L1 peptide: PD-L1 Long(19-27) Peptide sequence: FMTYWHLLNAFTVTVPKDL