A Phase-1-first in Man Study in Patients With CALR-mutant Myeloproliferative Neoplasms by Vaccinating With CALR Exon 9 Mutant Peptide
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Adverse events evaluated by CTCAE 4.03
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of essential thrombocythemia, post essential thrombocythemia myelofibrosis, prefibrotic myelofibrosis or primary myelofibrosis according to the World Health Organization criteria33
- •Verified mutation in CALR exon
- •Performance status ≤ 2 (ECOG-scale)
- •Expected survival > 3 months
- •Sufficient bone marrow function, i.e.
- •Leucocytes ≥ 1,5 x 109
- •Granulocytes ≥ 1,0 x 109
- •Thrombocytes ≥ 20 x 109
- •Hemoglobin ≥ 7 mmol/L
- •Creatinine < 2.5 upper normal limit, i.e. < 300 µmol/l
- •Sufficient liver function, i.e.
- •a. Alanine aminotransferase < 2.5 upper normal limit, i.e. ALAT <112 U/l b. Bilirubin < 30 U/l
- •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.
排除标准
- •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.
结局指标
主要结局
Adverse events evaluated by CTCAE 4.03
时间窗: 1 year
Adverse events are graded 1-5 according to the criteria
次要结局
- Immune responses(1 year)
研究者
Inge Marie Svane
Professor, MD, PhD
Herlev Hospital