Dual Vaccine Trial in Myeloproliferative Neoplasms

NCT04051307 | Completed Phase 1 DMC

• 1 other identifier: MPN19H2
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Polycythemia Vera; Essential Thrombocythemia

Outcome Measures

Primary Outcomes (1)

• Immune response

  T-cell cytokine release towards target antigens

  1 year

Secondary Outcomes (2)

• Adverse events evaluated by CTCAE v. 5.0

  1 year

• Clinical response

  10 year

Study Arms (1)

intervention

EXPERIMENTAL

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

Interventions

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

Peptide vaccination

Also known as: PD-L1Long

intervention

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

Peptide vaccination

Also known as: ARGLong2

intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• ALAT \< 2.5 upper normal limit, i.e. ALAT \<112 U/l
• 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.
• \. For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm.

You may not qualify if:

• 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.
• Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus.
• Acute or chronic viral or bacterial infection e.g. HIV, hepatitis or tuberculosis
• Serious known allergies or earlier anaphylactic reactions.
• Known sensibility to Montanide ISA-51
• 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.
• Pregnant and breastfeeding women.
• Fertile women not using secure contraception with a failure rate less than \< 1%
• Patients taking immune suppressive medications incl. systemic corticosteroids and methotrexate at the time of enrollment
• Psychiatric disorders that per investigator judgment could influence compliance.
• Treatment with other experimental drugs
• Treatment with other anti-cancer drugs - except IFN-a, hydroxyurea or anagrelide.
• Treatment with ruxolitinib.
• Treatment with chemotherapy or immune therapy (excluding IFN-a, hydroxyurea or anagrelide) within the last 28 days.

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (2)

Herlev Hospital

Herlev, Capital Region, 2730, Denmark

Location

National Center for Cancer Immune Therapy (CCIT-DK)

Herlev, 2730, Denmark

Location

Related Publications (1)

• Grauslund JH, Holmstrom MO, Martinenaite E, Lisle TL, Glockner HJ, El Fassi D, Klausen U, Mortensen REJ, Jorgensen N, Kjaer L, Skov V, Svane IM, Hasselbalch HC, Andersen MH. An arginase1- and PD-L1-derived peptide-based vaccine for myeloproliferative neoplasms: A first-in-man clinical trial. Front Immunol. 2023 Feb 23;14:1117466. doi: 10.3389/fimmu.2023.1117466. eCollection 2023.

  PMID: 36911725 DERIVED

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Study Officials

• Jacob H Grauslund, MD

  CENTER FOR CANCER IMMUNE THERAPY, CCIT-DK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof, MD

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: August 9, 2019
• Study Start: July 10, 2019
• Primary Completion: July 10, 2022
• Study Completion: July 10, 2022
• Last Updated: July 13, 2023

Record last verified: 2023-07

Locations

DK (2)