Mutant CALR-peptide Based Vaccine in Patients With Mutated CALR Myeloproliferative Neoplasm

NCT05025488 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GCO 22-1330
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Myelofibrosis; Essential Thrombocythemia; MPN

Keywords

CALR; Vaccine; MF; ET; peptide

Outcome Measures

Primary Outcomes (1)

• 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.

  32 weeks

Secondary Outcomes (7)

• Number of Adverse Events

  Week 32

• Number of laboratory abnormalities

  Baseline through Week 32

• Change in Immune Milieu Composite

  Baseline through Weeks 55 or 80

• Change in CALR VAF

  Baseline through Weeks 55 or 80

• Proportion of participants who normalize their platelet number

  Week 32 and weeks 55 or 80

Study Arms (1)

CALR mutated

EXPERIMENTAL

peptide-based vaccine in patients with myeloproliferative neoplasm (myelofibrosis and essential thrombocythemia) with CALR mutations

Drug: Peptide-based vaccine; Drug: Poly ICLC

Interventions

Peptide-based vaccine DRUG

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.

CALR mutated

Poly ICLC DRUG

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.

CALR mutated

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Marina Kremyanskaya: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis; Thrombocythemia, Essential

Interventions

poly ICLC

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Study Officials

• Marina Kremyanskaya, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Nina Bhardwaj, MD, PhD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Camelia Iancu-Rubin, PhD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Central Study Contacts

Marina Kremyanskaya, MD, PhD

CONTACT

(212) 241-4106; marina.kremyanskaya@mssm.edu

Gabriela Bello

CONTACT

(212) 241-0463; gabriela.bello@mssm.edu

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: Associate Professor

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: August 27, 2021
• Study Start: April 4, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)