E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myeloproliferative Neoplasms |
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E.1.1.1 | Medical condition in easily understood language |
Myeloproliferative Neoplasms, a group of cancer diseases of the bone marrow in which excess cells are produced. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028576 |
E.1.2 | Term | Myeloproliferative disorder |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015494 |
E.1.2 | Term | Essential thrombocythemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We will conduct a phase I-II study in patients with mutated MPN by vaccinating with PD-L1 and ARGLong2 peptides with Montanide ISA-51 (Seppic Inc., Paris, France) as adjuvant, to monitor the immunological response to vaccination and subsequently safety and toxicity. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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, i.e. a. Leucocytes ≥ 1,5 x 109 b. Granulocytes ≥ 1,0 x 109 c. Thrombocytes ≥ 20 x 109 d. Hemoglobin ≥ 5.5 mmol/L 6. Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l 7. Sufficient liver function, i.e. a. ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/l b. 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Immunogenicity of the two peptides-vaccines. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 3-6-7-9-12 vaccine rounds |
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E.5.2 | Secondary end point(s) |
Safety and toxicity, clinical effect of the vaccine will be described |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |