Dual Vaccine Trial in Myeloproliferative Neoplasms

NCT ID: NCT04051307

Last Updated: 2023-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-10
• Study Completion Date: 2022-07-10

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Peptide vaccination

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

Intervention Type: DRUG

Peptide vaccination

Interventions

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

Peptide vaccination

Intervention Type: DRUG

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

Peptide vaccination

Intervention Type: DRUG

Other Intervention Names

PD-L1Long; ARGLong2

Eligibility 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inge Marie Svane

OTHER

Sponsor Role: lead

Responsible Party

Inge Marie Svane

Prof, MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jacob H Grauslund, MD

Role: PRINCIPAL_INVESTIGATOR

CENTER FOR CANCER IMMUNE THERAPY, CCIT-DK

Locations

Herlev Hospital

Herlev, Capital Region, Denmark

National Center for Cancer Immune Therapy (CCIT-DK)

Herlev, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 36911725 (View on PubMed)

Other Identifiers

MPN19H2

Identifier Type: -

Identifier Source: org_study_id