MyelofibrosisPhase 1NCT05025488
Mutant CALR-peptide Based Vaccine in Patients With Mutated CALR Myeloproliferative Neoplasm
A Phase 1 study testing Peptide-based vaccine and Poly ICLC in people with Myelofibrosis and Essential Thrombocythemia, run by Marina Kremyanskaya at 1 site in United States.
Trial summary
The primary objective of this study is to assess the safety and tolerability of administrating mutated-CALR peptide Vaccine to patients with MPN. The researchers plan to enroll 10 patients over a 12 month period. Maximum length of participation in 80 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis, Essential Thrombocythemia, MPN
- What is being tested?
- Peptide-based vaccine and Poly ICLC
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2023to Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Subjects must be ≥18 years of age at the time of signing the informed consent form.
- Confirmed diagnosis of chronic phase MPN:
- Previously treated or relapsed/refectory high risk ET
- Low to intermediate 1 risk (DIPSS 0-1) PMF or ET-MF
- Verified mutation in CALR exon 9
- PS ≤ 2
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- Adequate organ function:
- Absolute neutrophil count ≥ 1000/mm3,
- Platelet count ≥ 50,000/mm3,
- Creatinine ≤ 2.5 mg/dL,
- Total bilirubin ≤ 2 mg/dL, (except in patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL)
- Transaminases < 3 times above the upper limits of the institutional normal.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to starting study medication and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks prior to first dose of vaccine. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy.
- Ability to understand and the willingness to sign a written informed consent.
- Ability to adhere to the study visit schedule and all protocol requirements.
- Subjects receiving cytoreductive therapy with hydroxyurea must be on a stable dose for at least 8 weeks prior to week 1.
Who cannot join
- Other invasive malignancy in the past 3 years except non-melanoma skin cancer, localized cured prostate cancer and early stage breast cancer on HRT.
- Active autoimmune disease.
- Uncontrolled serious infection.
- Known immunodeficiency.
- Pregnant and breastfeeding women.
- Not willing to use contraception.
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- Current use of immunosuppressive medications including steroids.
- Current JAK inhibitor use.
- Current use of IFN (use of anagrelide is permitted).
- Treatment with other experimental drugs within 30 days of week 1.
- Treatment with any MPN directed therapy unless otherwise noted within 5 half-lives of week 1.
- Any significant psychiatric/medical condition per investigators judgment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Phase I Open Label Peptide Based Vaccine in Patients With Myeloproliferative Neoplasm Harboring CALR Mutations
The primary objective of this study is to assess the safety and tolerability of administrating mutated-CALR peptide Vaccine to patients with MPN. The researchers plan to enroll 10 patients over a 12 month period. Maximum length of participation in 80 weeks. Patients will be asked to complete questionnaires, bone marrow biopsies, research lab collection, and standard of care lab draw. This research will be taking place only at The Mount Sinai Hospital, specifically at the Ruttenberg Treatment Center.
Read the detailed description
Current MPN treatments are geared towards symptom palliation and not on changing the natural course of the disease. Mutations in calreticulin gene (CALR) is the second most common driver mutation in ET and MF patients (30%). All CALR mutations identified to date in MPN patients result in the formation of an altered protein with an identical 36-amino acid sequence in the C-terminus. This altered protein results in a MPN-specific shared neo-antigen. The mutated CALR neoantigen present in patient with MPN represents an ideal antigen for targeted immunotherapy as it is stably and specifically expressed by the malignant cells and is absent in the normal tissues. CALR neoantigen is immunogenic, effector T cells are capable of recognizing this neo-antigen, and hematopoietic cells carrying the mutation can be potently killed by these specific effector T-cells in vitro.
The researchers believe that a mutated-CALR vaccine will enhance mutated-CALR-specific T cell immunity in MPN patients carrying CALR mutations, which in turn would target and eliminate CALR+ malignant cells, thereby leading to improved clinical outcomes in this patient population.
- Conditions
- Myelofibrosis, Essential Thrombocythemia, MPN
- Being tested
- Peptide-based vaccine, Poly ICLC
- Keywords
- CALR, Vaccine, MF, ET, peptide
- Medical subject headings
- Primary Myelofibrosis, Thrombocythemia, Essential
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peptide-based vaccineDrug
ten (10) doses of Mutant-CALR peptides with KLH as helper peptide (in the first vaccine only). Mutant-CALR vaccine will administered every 2 weeks for the first 4 doses and then every 4 weeks for additional 6 doses. Maintenance Treatment The protocol allows for a continued administration of up to four (4) additional Mutant-CALR vaccine and four (4) Poly-ICLC administrations, 12 weeks apart.
Poly ICLCDrug
ten (10) doses of Poly-ICLC. Poly-ICLC will be given on weeks 1, 3, 5, 7, 11, 15, 19, 23, 27 and 31. each Poly-ICLC dose must be given the day after the corresponding Mut-CALR vaccination.
| Study group | Role | What they receive |
|---|---|---|
| CALR mutated | Experimental | peptide-based vaccine in patients with myeloproliferative neoplasm (myelofibrosis and essential thrombocythemia) with CALR mutations Receives: Drug: Peptide-based vaccine; Drug: Poly ICLC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Dose Limiting Toxicity (DLT)
The Dose Limiting Toxicity (DLT) rate, defined as the proportion of patients with at least 1 grade 3 or higher AE considered to be at least possibly related to the treatment with Poly ICLC and CALR vaccines.
Measured: 32 weeks
Secondary outcomes (7)
Number of Adverse Events
The type, incidence, severity, seriousness, and relatedness of adverse events (AEs) per NCI CTCAE v5.0.
Measured: Week 32
Number of laboratory abnormalities
Number of observations, severity, and relatedness of clinical laboratory tests (hematology, biochemistry)
Measured: Baseline through Week 32
Change in Immune Milieu Composite
Changes in the immune milieu (which is a composite of expression of cytokines, presence of antibodies, alterations in number and phenotype of immune cells and induction of vaccine-specific T cell response) due to the vaccines as compared to baseline values.
Measured: Baseline through Weeks 55 or 80
Change in CALR VAF
The % change in driver mutation burden (CALR VAF) as compared to baseline
Measured: Baseline through Weeks 55 or 80
Proportion of participants who normalize their platelet number
The proportion of patients who normalize their platelet number and/or achieve platelets less than 600 if started with platelet above 600.
Measured: Week 32 and weeks 55 or 80
Proportion of participants achieving response
The proportion of patients achieving response or improvement in their disease status by ELN/IWG criteria for the categories: Complete Response; Partial Response; Clinical Improvement and Stable Disease
Measured: Baseline and Week 32
Myelofibrosis Symptom Assessment Form (MF-SAFv4.0)
The proportion of patients who achieve improvement in quality of life as assessed by the by the Myelofibrosis Symptom Assessment Form. Each of the items are scored 0 to 10, with total score from 0 to 100, with higher score indicating more symptoms.
Measured: Week 32 and weeks 55 or 80
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start4 Apr 2023
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelofibrosisStudies 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marina Kremyanskaya
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Marina Kremyanskaya, Icahn School of Medicine at Mount Sinai
- Investigators
- Marina Kremyanskaya, MD, PhD, Principal investigator, Icahn School of Medicine at Mount SinaiNina Bhardwaj, MD, PhD, Study chair, Icahn School of Medicine at Mount SinaiCamelia Iancu-Rubin, PhD, Study chair, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05025488
- Sponsor's protocol ID
- GCO 22-1330
- Status last verified
- Jun 2026
- First submitted
- 24 Aug 2021
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Not determined at this time
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open Label Peptide Based Vaccine in Patients With Myeloproliferative Neoplasm Harboring CALR Mutations
- ClinicalTrials.gov ID
- NCT05025488
- Acronym / sponsor ID
- GCO 22-1330
- Conditions
- Myelofibrosis, Essential Thrombocythemia, MPN
- Keywords
- CALR, Vaccine, MF, ET, peptide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Marina KremyanskayaUniversity, hospital or other
- Study start
- 4 Apr 2023 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 27 Aug 2021 (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.
The primary objective of this study is to assess the safety and tolerability of administrating mutated-CALR peptide Vaccine to patients with MPN. The researchers plan to enroll 10 patients over a 12 month period. Maximum length of participation in 80 weeks. Patients will be asked to complete questionnaires, bone marrow biopsies, research lab collection, and standard of care lab draw. This research will be taking place only at The Mount Sinai Hospital, specifically at the Ruttenberg Treatment Center.
Detailed description
Current MPN treatments are geared towards symptom palliation and not on changing the natural course of the disease. Mutations in calreticulin gene (CALR) is the second most common driver mutation in ET and MF patients (30%). All CALR mutations identified to date in MPN patients result in the formation of an altered protein with an identical 36-amino acid sequence in the C-terminus. This altered protein results in a MPN-specific shared neo-antigen. The mutated CALR neoantigen present in patient with MPN represents an ideal antigen for targeted immunotherapy as it is stably and specifically expressed by the malignant cells and is absent in the normal tissues. CALR neoantigen is immunogenic, effector T cells are capable of recognizing this neo-antigen, and hematopoietic cells carrying the mutation can be potently killed by these specific effector T-cells in vitro.
The researchers believe that a mutated-CALR vaccine will enhance mutated-CALR-specific T cell immunity in MPN patients carrying CALR mutations, which in turn would target and eliminate CALR+ malignant cells, thereby leading to improved clinical outcomes in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CALR mutated | Experimental | Drug: Peptide-based vaccine, Drug: Poly ICLCpeptide-based vaccine in patients with myeloproliferative neoplasm (myelofibrosis and essential thrombocythemia) with CALR mutations |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Subjects must be ≥18 years of age at the time of signing the informed consent form.
- Confirmed diagnosis of chronic phase MPN:
- Previously treated or relapsed/refectory high risk ET
- Low to intermediate 1 risk (DIPSS 0-1) PMF or ET-MF
- Verified mutation in CALR exon 9
Key exclusion criteria (12 listed)
- Other invasive malignancy in the past 3 years except non-melanoma skin cancer, localized cured prostate cancer and early stage breast cancer on HRT.
- Active autoimmune disease.
- Uncontrolled serious infection.
- Known immunodeficiency.
- Pregnant and breastfeeding women.
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 |
|---|---|---|
| Peptide-based vaccineten (10) doses of Mutant-CALR peptides with KLH as helper peptide (in the first vaccine only). Mutant-CALR vaccine will administered every 2 weeks for the first 4 doses and then every 4 weeks for additional 6 doses. Maintenance Treatment The protocol allows for a continued administration of up to four (4) additional Mutant-CALR vaccine and four (4) Poly-ICLC administrations, 12 weeks apart. | Drug | CALR mutated |
| Poly ICLCten (10) doses of Poly-ICLC. Poly-ICLC will be given on weeks 1, 3, 5, 7, 11, 15, 19, 23, 27 and 31. each Poly-ICLC dose must be given the day after the corresponding Mut-CALR vaccination. | Drug | CALR mutated |
Primary outcome
Number of Participants with Dose Limiting Toxicity (DLT)
Time frame: 32 weeks
The Dose Limiting Toxicity (DLT) rate, defined as the proportion of patients with at least 1 grade 3 or higher AE considered to be at least possibly related to the treatment with Poly ICLC and CALR vaccines.
7 secondary outcomes
Number of Adverse Events
Time frame: Week 32
Number of laboratory abnormalities
Time frame: Baseline through Week 32
Change in Immune Milieu Composite
Time frame: Baseline through Weeks 55 or 80
Change in CALR VAF
Time frame: Baseline through Weeks 55 or 80
Proportion of participants who normalize their platelet number
Time frame: Week 32 and weeks 55 or 80
Proportion of participants achieving response
Time frame: Baseline and Week 32
Myelofibrosis Symptom Assessment Form (MF-SAFv4.0)
Time frame: Week 32 and weeks 55 or 80
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- Individual participant dataSharing planned: No. Not determined at this time
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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.
Marina Kremyanskaya, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
Nina Bhardwaj, MD, PhD study chair
Icahn School of Medicine at Mount Sinai
Camelia Iancu-Rubin, PhD study chair
Icahn School of Medicine at Mount Sinai
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 Peptide-based vaccine and Poly ICLC in people with Myelofibrosis and Essential Thrombocythemia, run by Marina Kremyanskaya at 1 site in United States.
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 16 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 28 Sep 2026. 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
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?
Number of Participants with Dose Limiting Toxicity (DLT) (time frame: 32 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Sep 2026.