Vaccination With PD-L1 Peptide With Montanide Against Multiple Myeloma After High Dose Chemotherapy With Stem Cell Support. A Phase I First-in-human Study.
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
- 2
- 主要终点
- Incidence of toxicity
研究概览
简要总结
Title: Vaccination with PD-L1 peptide with Montanide against multiple myeloma after high dose chemotherapy with stem cell support. A phase I first-in-human study.
Hypothesis: In this trial the investigators assess a new immunotherapeutic strategy targeting the immune checkpoint molecule PD-L1 to investigate the potential of vaccination against PD-L1 as a possible anticancer target.
详细描述
Background: Multiple myeloma is the second most common hematologic cancer which is despite advances in treatment is still incurable for most patients.
In this trial the investigators assess a new immunotherapeutic strategy targeting the immune checkpoint molecule PD-L1 to investigate the potential of vaccination against PD-L1 as a possible anticancer target.
PD-L1 has been recognized as an important factor in immune regulation and development of immune tolerance in the microenvironment of cancer cells. Cells that express PD-L1 on their surface are known to inhibit the immune system. As seen with the recent advances in immunotherapy against cancer with antibodies against PD-L1, the the immunosuppressive role of the molecule PD-L1 can be antagonized to the benefit of patients with cancer. PD-L1 is expressed on both cancer cells, antigen presenting cells and immunosuppressive cells in the tumor micro-environment. Vaccination against PD-L1 is therefore two sided. The investigators aim to stimulate PD-L1 specific T-cells, hence eliminating both PD-L1 positive tumor cells as well as PD-L1 positive immunosuppressive and antigen presenting cells in the tumor microenvironment. The primary endpoints are safety and toxicity evaluation. Secondary endpoint is immunological response. Clinical response will be described.
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
- •Histologically verified multiple myeloma
- •Newly treated with HDT and no signs of relapse
- •Age ≥18 years
- •Performance status ≤ 2 (ECOG-scale)
- •Expected survival > 3 months
- •Sufficiently regenerated bone marrow function, i.e.
- •Leucocytes ≥ 1,5 x 109
- •Granulocytes ≥ 1,0 x 109
- •Thrombocytes ≥ 20 x 109
- •Creatinine < 2.5 upper normal limit, i.e. < 300 μmol/l
- •Sufficient liver function, i.e.
- •ALAT < 2.5 upper normal limit, i.e. ALAT <112 U/l
- •Bilirubin < 30 U/l
- •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
- •Non-secretory myeloma
- •Other malignancies in the medical history excluding squamous cell carcinoma of the skin and patients cured for another malignant disease with no sign of relapse three years after ended treatment.
- •Significant medical condition per investigators judgement e.g. severe Asthma/COPD, poorly regulated heart condition, insulin dependent diabetes mellitus.
- •Acute or chronic viral infection e.g. HIV, hepatitis or tuberculosis
- •Serious known allergies or earlier anaphylactic reactions.
- •Known sensibility towards 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 bisphosphonates and denosumab
- •Patients with active uncontrolled hypercalcemia
- •Patients who have received chemotherapy, immune therapy, radiation therapy within the last 28 days.
结局指标
主要结局
Incidence of toxicity
时间窗: 12 months
CTCAE = Common Terminology Criteria for Adverse Events v. 4.0 will be used for registration of toxicity
次要结局
- Evaluation of immunological responses(12 months)
研究者
Lene Meldgaard Knudsen
MD, DMSc, Head of Department, Department of Haematology, Universityhospital Herlev and Gentofte
Herlev Hospital