Peptide Vaccination in Combination With Azacitidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia - A Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
The purpose of this phase I study is to investigate the combination of hypomethylating agents with experimental peptide vaccination against four selected tumor antigens, known to be upregulated in response to hypomethylating agents, in patients with high risk myelodysplastic syndrome and acute myeloid leukemia.
详细描述
INTRODUCTION
Patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), who cannot be offered curative treatment, have a poor prognosis with a median survival of 11.5 months. There is currently only one registered drug that has been shown to prolong survival in this patient group; the hypomethylating agent azacitidine (also known as 5-azacytidine or Vidaza®). The treatment is not curative, but increases the median survival to approximately two years. The dominant cause of death is progressive disease, and there is a huge need for new treatment options.
In this study we will combine experimental immunotherapy of peptide vaccination with standard therapy of azacitidine for treatment of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. Our project is expected to expand the knowledge in regard to combination of immunotherapy and conventional treatment and will be essential for further development of this treatment modality.
MYELODYSPLASTIC SYNDROME (MDS)
Accumulation of both genetic and epigenetic changes in hematopoietic stem cells is considered the background for development of MDS. In the early stages of the disease, there is increased apoptosis, but as the disease progresses to high-risk MDS or AML there is an accumulation of chromosomal breakage, point mutations and promoter hypermethylation of tumor suppressor genes, resulting in a more aggressive and proliferative disease. The clinical symptoms are anemia, repeated infections and bleeding episodes associated with the dysfunctional bone marrow.
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
- •Participants must have received 6 courses of azacitidine and been evaluated with response to treatment.
- •Histologically confirmed high-risk MDS or AML (<30% blasts) and a normo- or hypercellular marrow after 6 courses of azacitidine.
- •Indication for continued treatment with azacitidine.
- •Age >18 years.
- •Signed consent form after receiving both written and oral information.
- •The patients must be willing to follow the scheduled treatment and sampling.
排除标准
- •Hypocellular bone marrow after 6 courses of azacitidine.
- •Additional active cancer disease. Participants treated for a second malignancy may be included if the patient is without evidence of disease at least 2 years after completion of treatment.
- •Participants with a known hypersensitivity to any of the active substances or to any of the excipients.
- •Participants with secondary MDS or AML
- •Severe allergies or previous anaphylactic reactions.
- •Active autoimmune disease, for example autoimmune neutropenia/ thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, Sjögren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addison's disease, Hashimoto's thyroiditis, Grave's disease.
- •Concomitant treatment with systemic immunosuppressive medications (including prednisone, methotrexate etc.). Participants are allowed to receive up to 10 mg prednisone at the days of azacitidine injection.
- •Concomitant treatment with other experimental drugs.
- •Concomitant treatment with other systemic anti-cancer therapy.
- •Pregnant or breastfeeding females.
研究组 & 干预措施
Vaccination
Azacitidine + NPMW-peptide vaccine
干预措施: NPMW-peptide vaccine (Biological)
Vaccination
Azacitidine + NPMW-peptide vaccine
干预措施: Azacitidine (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: Through study completion, up to 24 months.
The safety of combining azacitidine treatment with this peptide vaccine will be judged on basis of the reported adverse events during the study period.
次要结局
- Immunological evaluation(weeks: 0, 1, 9, 21. Thereafter months: 12, 18, 24)
研究者
Daniel El Fassi
Clinical Associate Professor
Herlev Hospital