A Phase I Open Label Peptide Based Vaccine in Patients With Myeloproliferative Neoplasm Harboring CALR Mutations
Overview
- Phase
- Phase 1
- Intervention
- Peptide-based vaccine
- Conditions
- Myelofibrosis
- Sponsor
- Marina Kremyanskaya
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Number of Participants with Dose Limiting Toxicity (DLT)
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
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.
Investigators
Marina Kremyanskaya
Associate Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •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
- •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)
Exclusion Criteria
- •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
Arms & Interventions
CALR mutated
peptide-based vaccine in patients with myeloproliferative neoplasm (myelofibrosis and essential thrombocythemia) with CALR mutations
Intervention: Peptide-based vaccine
CALR mutated
peptide-based vaccine in patients with myeloproliferative neoplasm (myelofibrosis and essential thrombocythemia) with CALR mutations
Intervention: Poly ICLC
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Change in Immune Milieu Composite(Baseline through Weeks 55 or 80)
- Proportion of participants who normalize their platelet number(Week 32 and weeks 55 or 80)
- Myelofibrosis Symptom Assessment Form (MF-SAFv4.0)(Week 32 and weeks 55 or 80)
- Number of laboratory abnormalities(Baseline through Week 32)
- Proportion of participants achieving response(Baseline and Week 32)
- Number of Adverse Events(Week 32)
- Change in CALR VAF(Baseline through Weeks 55 or 80)