Myeloproliferative Neoplasm, UnclassifiablePhase 1NCT03566446
CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms
A Phase 1 study testing CALRLong36 peptide in people with Myeloproliferative Neoplasm, Unclassifiable and Essential Thrombocythemia, run by Inge Marie Svane at 1 site in Denmark.
Trial summary
A phase-I-first in man study in patients with calreticulin(CALR)-mutant MPN by vaccinating with exon 9 mutated peptide with the adjuvant Montanide ISA-51 to monitor safety and toxicity and the immunological response to vaccination. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloproliferative Neoplasm, Unclassifiable, Essential Thrombocythemia, Myelofibrosis
- What is being tested?
- CALRLong36 peptide
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Jun 2018to 30 Apr 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Diagnosis of essential thrombocythemia, post essential thrombocythemia myelofibrosis, prefibrotic myelofibrosis or primary myelofibrosis according to the World Health Organization criteria33 2. Verified mutation in CALR exon 9. 4. Performance status ≤ 2 (ECOG-scale) 5. Expected survival > 3 months 6. Sufficient bone marrow function, i.e.
- Leucocytes ≥ 1,5 x 109
- Granulocytes ≥ 1,0 x 109
- Thrombocytes ≥ 20 x 109
- Hemoglobin ≥ 7 mmol/L 7. Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l 8. Sufficient liver function, i.e.
- Alanine aminotransferase < 2.5 upper normal limit, i.e. ALAT <112 U/l b. Bilirubin < 30 U/l 9. 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.
- 10. For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm.
Who cannot join
- Other malignancies in the medical history excluding squamous cell carcinoma. Patients cured for another malignant disease with no sign of relapse three years after ended treatment is allowed to enter the protocol.
- Significant medical condition per investigators judgement e.g. severe Asthma/chronic obstructive pulmonary disease , 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.
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- Pregnant and breastfeeding women.
- Fertile women not using secure contraception with a failure rate less than < 1%
- Patients taking immune suppressive medications incl. 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 interferon (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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase-1-first in Man Study in Patients With CALR-mutant Myeloproliferative Neoplasms by Vaccinating With CALR Exon 9 Mutant Peptide
A phase-I-first in man study in patients with calreticulin(CALR)-mutant MPN by vaccinating with exon 9 mutated peptide with the adjuvant Montanide ISA-51 to monitor safety and toxicity and the immunological response to vaccination.
Read the detailed description
The Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPN) are acquired cancer diseases, that arise due to mutations in the hematopoietic stem cells in the bone marrow. Median age at diagnosis is approximately 65 years of age and approximately 400 Danes are diagnosed with MPN annually. The MPN comprise essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). In December 2013 two independent research groups reported on the occurrence of somatic mutations in exon 9 of the calreticulin gene in patients with ET and PMF.
The overall rationale for a vaccine with CALR-mutant epitopes is that it will initiate a CALR-mutant specific immune response, which will "release the brakes" on the CALR-mutant specific immune response.
10 patients treated with standard therapy are needed for the trial and each patient will receive 15 vaccinations over the course of one year.
- Being tested
- CALRLong36 peptide
- Keywords
- CALR mutation
- Medical subject headings
- Myeloproliferative Disorders, Thrombocythemia, Essential, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CALRLong36 peptideBiological
200 ug CALRLong36 peptide in water mixed with 500ul montanide
| Study group | Role | What they receive |
|---|---|---|
| 36 aminoacid CALR exon 9 mutated peptide | Experimental | 15 vaccines, over the course of 1 year Receives: Biological: CALRLong36 peptide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events evaluated by CTCAE 4.03
Adverse events are graded 1-5 according to the criteria
Measured: 1 year
Secondary outcomes (1)
Immune responses
T-cell cytokine release towards target antigens
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2018
- Study start20 Jun 2018
- Primary completion20 Feb 2020
- Study completion30 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myeloproliferative Neoplasm, UnclassifiableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inge Marie Svane
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Inge Marie Svane, Herlev Hospital
- Investigators
- Jacob H Grauslund, MD, Principal investigator, Center for Cancer Immune Therapy, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03566446
- Sponsor's protocol ID
- MPN1801
- Other IDs
- 2018-000132-10, 2018
- Status last verified
- Jul 2023
- First submitted
- 11 Jun 2018
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Handlos Grauslund J, Holmstrom MO, Jorgensen NG, Klausen U, Weis-Banke SE, El Fassi D, Schollkopf C, Clausen MB, Gjerdrum LMR, Breinholt MF, Kjeldsen JW, Hansen M, Koschmieder S, Chatain N, Novotny GW, Petersen J, Kjaer L, Skov V, Met O, Svane IM, Hasselbalch HC, Andersen MH. Therapeutic Cancer Vaccination With a Peptide Derived From the Calreticulin Exon 9 Mutations Induces Strong Cellular Immune Responses in Patients With CALR-Mutant Chronic Myeloproliferative Neoplasms. Front Oncol. 2021 Feb 26;11:637420. doi: 10.3389/fonc.2021.637420. eCollection 2021.
PubMed 33718228
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase-1-first in Man Study in Patients With CALR-mutant Myeloproliferative Neoplasms by Vaccinating With CALR Exon 9 Mutant Peptide
- ClinicalTrials.gov ID
- NCT03566446
- Acronym / sponsor ID
- MPN1801
- Keywords
- CALR mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Inge Marie SvaneUniversity, hospital or other
- Study start
- 20 Jun 2018 (actual)
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 30 Apr 2021 (actual)
- First posted
- 25 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase-I-first in man study in patients with calreticulin(CALR)-mutant MPN by vaccinating with exon 9 mutated peptide with the adjuvant Montanide ISA-51 to monitor safety and toxicity and the immunological response to vaccination.
Detailed description
The Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPN) are acquired cancer diseases, that arise due to mutations in the hematopoietic stem cells in the bone marrow. Median age at diagnosis is approximately 65 years of age and approximately 400 Danes are diagnosed with MPN annually. The MPN comprise essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). In December 2013 two independent research groups reported on the occurrence of somatic mutations in exon 9 of the calreticulin gene in patients with ET and PMF.
The overall rationale for a vaccine with CALR-mutant epitopes is that it will initiate a CALR-mutant specific immune response, which will "release the brakes" on the CALR-mutant specific immune response.
10 patients treated with standard therapy are needed for the trial and each patient will receive 15 vaccinations over the course of one year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 36 aminoacid CALR exon 9 mutated peptide | Experimental | Biological: CALRLong36 peptide15 vaccines, over the course of 1 year |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. Diagnosis of essential thrombocythemia, post essential thrombocythemia myelofibrosis, prefibrotic myelofibrosis or primary myelofibrosis according to the World Health Organization criteria33 2. Verified mutation in CALR exon 9. 4. Performance status ≤ 2 (ECOG-scale) 5. Expected survival > 3 months 6. Sufficient bone marrow function, i.e.
- Leucocytes ≥ 1,5 x 109
- Granulocytes ≥ 1,0 x 109
- Thrombocytes ≥ 20 x 109
- Hemoglobin ≥ 7 mmol/L 7. Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l 8. Sufficient liver function, i.e.
Key exclusion criteria (14 listed)
- Other malignancies in the medical history excluding squamous cell carcinoma. Patients cured for another malignant disease with no sign of relapse three years after ended treatment is allowed to enter the protocol.
- Significant medical condition per investigators judgement e.g. severe Asthma/chronic obstructive pulmonary disease , 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CALRLong36 peptide200 ug CALRLong36 peptide in water mixed with 500ul montanide | Biological | 36 aminoacid CALR exon 9 mutated peptide |
Primary outcome
Adverse events evaluated by CTCAE 4.03
Time frame: 1 year
Adverse events are graded 1-5 according to the criteria
1 secondary outcome
Immune responses
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Derived from this study: PubMed 33718228Handlos Grauslund J, Holmstrom MO, Jorgensen NG, Klausen U, Weis-Banke SE, El Fassi D, Schollkopf C, Clausen MB, Gjerdrum LMR, Breinholt MF, Kjeldsen JW, Hansen M, Koschmieder S, Chatain N, Novotny GW, Petersen J, Kjaer L, Skov V, Met O, Svane IM, Hasselbalch HC, Andersen MH. Therapeutic Cancer Vaccination With a Peptide Derived From the Calreticulin Exon 9 Mutations Induces Strong Cellular Immune Responses in Patients With CALR-Mutant Chronic Myeloproliferative Neoplasms. Front Oncol. 2021 Feb 26;11:637420. doi: 10.3389/fonc.2021.637420. eCollection 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacob H Grauslund, MD principal investigator
Center for Cancer Immune Therapy, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CALRLong36 peptide in people with Myeloproliferative Neoplasm, Unclassifiable and Essential Thrombocythemia, run by Inge Marie Svane at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events evaluated by CTCAE 4.03 (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03566446, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2023.