NCT03566446

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2018

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 11, 2018

Completed
9 days until next milestone

Study Start

First participant enrolled

June 20, 2018

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 25, 2018

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 20, 2020

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2021

Completed
Last Updated

July 13, 2023

Status Verified

July 1, 2023

Enrollment Period

1.7 years

First QC Date

June 11, 2018

Last Update Submit

July 12, 2023

Conditions

Keywords

CALR mutation

Outcome Measures

Primary Outcomes (1)

  • Adverse events evaluated by CTCAE 4.03

    Adverse events are graded 1-5 according to the criteria

    1 year

Secondary Outcomes (1)

  • Immune responses

    1 year

Other Outcomes (4)

  • Mutational status

    1 year

  • Bone marrow response

    1 year

  • mutational landscape change

    1 year

  • +1 more other outcomes

Study Arms (1)

36 aminoacid CALR exon 9 mutated peptide

EXPERIMENTAL

15 vaccines, over the course of 1 year

Biological: CALRLong36 peptide

Interventions

200 ug CALRLong36 peptide in water mixed with 500ul montanide

36 aminoacid CALR exon 9 mutated peptide

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \. 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.
  • 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.
  • \. For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm.

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Herlev Hospital

Herlev, Capital Region, 2730, Denmark

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Myeloproliferative DisordersThrombocythemia, EssentialPrimary Myelofibrosis

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesBlood Coagulation DisordersThrombocytosisBlood Platelet DisordersHemorrhagic Disorders

Study Officials

  • Jacob H Grauslund, MD

    Center for Cancer Immune Therapy, Denmark

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor, MD, PhD

Study Record Dates

First Submitted

June 11, 2018

First Posted

June 25, 2018

Study Start

June 20, 2018

Primary Completion

February 20, 2020

Study Completion

April 30, 2021

Last Updated

July 13, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will not share

Locations