A phase-I-first in man study in patients with calreticulin(CALR)-mutant MPN by vaccinating with exon 9 mutated peptide with the adjuvant Montanide ISA-51 to monitor safety and toxicity and the immunological response to vaccination.

The Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPN) are acquired cancer diseases, that arise due to mutations in the hematopoietic stem cells in the bone marrow. Median age at diagnosis is approximately 65 years of age and approximately 400 Danes are diagnosed with MPN annually. The MPN comprise essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). In December 2013 two independent research groups reported on the occurrence of somatic mutations in exon 9 of the calreticulin gene in patients with ET and PMF.

The overall rationale for a vaccine with CALR-mutant epitopes is that it will initiate a CALR-mutant specific immune response, which will "release the brakes" on the CALR-mutant specific immune response.

10 patients treated with standard therapy are needed for the trial and each patient will receive 15 vaccinations over the course of one year.

Inclusion Criteria:

1. Diagnosis of essential thrombocythemia, post essential thrombocythemia myelofibrosis, prefibrotic myelofibrosis or primary myelofibrosis according to the World Health Organization criteria33 2. Verified mutation in CALR exon 9. 4. Performance status ≤ 2 (ECOG-scale) 5. Expected survival > 3 months 6. Sufficient bone marrow function, i.e.

1. Leucocytes ≥ 1,5 x 109
2. Granulocytes ≥ 1,0 x 109
3. Thrombocytes ≥ 20 x 109
4. Hemoglobin ≥ 7 mmol/L 7. Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l 8. Sufficient liver function, i.e.

a. Alanine aminotransferase < 2.5 upper normal limit, i.e. ALAT <112 U/l b. Bilirubin < 30 U/l 9. 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.

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

Exclusion Criteria:

1. Other malignancies in the medical history excluding squamous cell carcinoma. Patients cured for another malignant disease with no sign of relapse three years after ended treatment is allowed to enter the protocol.
2. Significant medical condition per investigators judgement e.g. severe Asthma/chronic obstructive pulmonary disease , 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. 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 interferon (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.