Back to resultsDual Vaccine Trial in Myeloproliferative Neoplasms
Primary Purpose
Polycythemia Vera, Essential Thrombocythemia
Status
Completed
Phase
Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
PD-L1 peptide: PD-L1 Long(19-27) Peptide sequence: FMTYWHLLNAFTVTVPKDL
Arginase1 peptide: ArgLong2(169-206) Peptide sequence ISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRL
Sponsored by
About this trial
This is an interventional treatment trial for Polycythemia Vera
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.
- 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.
9. For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm.
Exclusion criteria
- 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.
Sites / Locations
- Herlev Hospital
- National Center for Cancer Immune Therapy (CCIT-DK)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
intervention
Arm 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.
Outcomes
Primary Outcome Measures
Immune response
T-cell cytokine release towards target antigens
Secondary Outcome Measures
Adverse events evaluated by CTCAE v. 5.0
Adverse events are graded 1-5 according to the criteria
Clinical response
Vaccinations will induce clinical response in 2 patients, either partial response or better, according response criteria for PV and ET or clinical response as a reduction of mutated allelic burden - 10% from baseline at any time.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04051307
Brief Title
Dual Vaccine Trial in Myeloproliferative Neoplasms
Official Title
Dual Vaccine Trial in Myeloproliferative Neoplasms
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
July 10, 2019 (Actual)
Primary Completion Date
July 10, 2022 (Actual)
Study Completion Date
July 10, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Inge Marie Svane
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycythemia Vera, Essential Thrombocythemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
intervention
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
PD-L1 peptide: PD-L1 Long(19-27) Peptide sequence: FMTYWHLLNAFTVTVPKDL
Other Intervention Name(s)
PD-L1Long
Intervention Description
Peptide vaccination
Intervention Type
Drug
Intervention Name(s)
Arginase1 peptide: ArgLong2(169-206) Peptide sequence ISAKDIVYIGLRDVDPGEHYILKTLGIKYFSMTEVDRL
Other Intervention Name(s)
ARGLong2
Intervention Description
Peptide vaccination
Primary Outcome Measure Information:
Title
Immune response
Description
T-cell cytokine release towards target antigens
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Adverse events evaluated by CTCAE v. 5.0
Description
Adverse events are graded 1-5 according to the criteria
Time Frame
1 year
Title
Clinical response
Description
Vaccinations will induce clinical response in 2 patients, either partial response or better, according response criteria for PV and ET or clinical response as a reduction of mutated allelic burden - 10% from baseline at any time.
Time Frame
10 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
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.
9. For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm.
Exclusion criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacob H Grauslund, MD
Organizational Affiliation
CENTER FOR CANCER IMMUNE THERAPY, CCIT-DK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Herlev Hospital
City
Herlev
State/Province
Capital Region
ZIP/Postal Code
2730
Country
Denmark
Facility Name
National Center for Cancer Immune Therapy (CCIT-DK)
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Dual Vaccine Trial in Myeloproliferative Neoplasms
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