Inclusion Criteria.

• - Subjects must be ≥18 years of age at the time of signing the informed consent form.

• - Confirmed diagnosis of chronic phase MPN: high risk ET (HU failure/intolerance), low-intermediate 1 (DIPSS 0-1) PMF.

• - Verified mutation in CALR exon 9.

• - PS ≤ 2.

• - Adequate organ function: - Absolute neutrophil count ≥ 1000/mm3.

• - Platelet count ≥ 50,000/mm3, - Creatinine ≤ 2.5 mg/dL, - Total bilirubin ≤ 2 mg/dL, (except in patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL) - Transaminases 3 times above the upper limits of the institutional normal.

• - INR<2 if off of anticoagulation.

Patients on anticoagulation therapy with an INR>2 may be enrolled at the discretion of the investigator if have not had any episodes of severe hemorrhage.

• - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to starting study medication and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before prior to first dose of vaccine.

FCBP must also agree to ongoing pregnancy testing. Men must agree to use a condom during sexual contact with a female of child bearing potential even if have had a successful vasectomy.

• - Ability to understand and the willingness to sign a written informed consent.

• - Ability to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria.

• - Other invasive malignancy in the past 3 years except non-melanoma skin cancer, localized cured prostate cancer and early stage breast cancer on HRT.

• - Active autoimmune disease.

• - Uncontrolled serious infection.

• - Known immunodeficiency.

• - Pregnant and breastfeeding women.

• - Not willing to use contraception.

• - Current use of immunosuppressive medications including steroids.

• - Current Ruxolitinib or Fedratinib use.

• - Current use of hydroxyurea.

• - Current use of INF (use of anagrelide is permitted) - Treatment with other experimental drugs.

- Any significant psychiatric/medical condition per investigators judgment

Current MPN treatments are geared towards symptom palliation and not on changing the natural course of the disease. Mutations in calreticulin gene (CALR) is the second most common driver mutation in ET and MF patients (30%). All CALR mutations identified to date in MPN patients result in the formation of an altered protein with an identical 36-amino acid sequence in the C-terminus. This altered protein results in a MPN-specific shared neo-antigen. The mutated CALR neoantigen present in patient with MPN represents an ideal antigen for targeted immunotherapy as it is stably and specifically expressed by the malignant cells and is absent in the normal tissues. CALR neoantigen is immunogenic, effector T cells are capable of recognizing this neo-antigen, and hematopoietic cells carrying the mutation can be potently killed by these specific effector T-cells in vitro. The researchers believe that a mutated-CALR vaccine will enhance mutated-CALR-specific T cell immunity in MPN patients carrying CALR mutations, which in turn would target and eliminate CALR+ malignant cells, thereby leading to improved clinical outcomes in this patient population.

Arms

Experimental: CALR mutated

peptide-based vaccine in patients with myeloproliferative neoplasm (myelofibrosis and essential thrombocythemia) with CALR mutations

Interventions

Drug: - Peptide-based vaccine

ten (10) doses of Mutant-CALR peptides with KLH as helper peptide (in the first vaccine only). Mutant-CALR vaccine will administered every 2 weeks for the first 4 doses and then every 4 weeks for additional 6 doses. Maintenance Treatment The protocol allows for a continued administration of up to four (4) additional Mutant-CALR vaccine and four (4) Poly-ICLC administrations, 12 weeks apart.

Drug: - Poly ICLC

ten (10) doses of Poly-ICLC. Poly-ICLC will be given on weeks 1, 3, 5, 7, 11, 15, 19, 23, 27 and 31. each Poly-ICLC dose must be given the day after the corresponding Mut-CALR vaccination.