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CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03566446
Recruitment Status : Active, not recruiting
First Posted : June 25, 2018
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Inge Marie Svane, Herlev Hospital

Tracking Information
First Submitted Date  ICMJE June 11, 2018
First Posted Date  ICMJE June 25, 2018
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE June 20, 2018
Estimated Primary Completion Date February 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2018)
Adverse events evaluated by CTCAE 4.03 [ Time Frame: 1 year ]
Adverse events are graded 1-5 according to the criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2018)
Immune responses [ Time Frame: 1 year ]
T-cell cytokine release towards target antigens
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 21, 2018)
  • Mutational status [ Time Frame: 1 year ]
    CALR-mutational status
  • Bone marrow response [ Time Frame: 1 year ]
    bone marrow description
  • mutational landscape change [ Time Frame: 1 year ]
    Next Generation Sequencing pre- and post-treatment
  • Overall response [ Time Frame: 1 year ]
    Revised response criteria by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms
Official Title  ICMJE A Phase-1-first in Man Study in Patients With CALR-mutant Myeloproliferative Neoplasms by Vaccinating With CALR Exon 9 Mutant Peptide
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myeloproliferative Neoplasm, Unclassifiable
  • Essential Thrombocythemia
  • Myelofibrosis
Intervention  ICMJE Biological: CALRLong36 peptide
200 ug CALRLong36 peptide in water mixed with 500ul montanide
Study Arms  ICMJE Experimental: 36 aminoacid CALR exon 9 mutated peptide
15 vaccines, over the course of 1 year
Intervention: Biological: CALRLong36 peptide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 21, 2018)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2021
Estimated Primary Completion Date February 20, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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.

  1. Leucocytes ≥ 1,5 x 109
  2. Granulocytes ≥ 1,0 x 109
  3. Thrombocytes ≥ 20 x 109
  4. Hemoglobin ≥ 7 mmol/L 7. Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l 8. Sufficient liver function, i.e.

a. 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.

Exclusion Criteria:

  1. 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.
  2. Significant medical condition per investigators judgement e.g. severe Asthma/chronic obstructive pulmonary disease , 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. 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 interferon (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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03566446
Other Study ID Numbers  ICMJE MPN1801
2018-000132-10 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Inge Marie Svane, Herlev Hospital
Study Sponsor  ICMJE Inge Marie Svane
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jacob H Grauslund, MD Center for Cancer Immune Therapy, Denmark
PRS Account Herlev Hospital
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP