Peptide Vaccination With PD-L1 and PD-L2 Peptides in Untreated Chronic Lymphatic Leukemia.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Clinical response according to IW-CLL
研究概览
简要总结
This study is investigating the efficacy of PD-L1 and PD-L2 peptides in untreated CLL patients with unmutated IGHV gene status.
详细描述
Chronic lymphocytic leukemia (CLL) is an incurable disease with the unmutated immunoglobulin heavy chain variable region (IGHV) gene status being an unfavorable prognostic marker. These patients have shorter time to first treatment which consist of toxic chemotherapy.
Programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) are immune checkpoints hampering immune responses in many tumors including CLL. These proteins are expressed by suppressive bystander cells as well as CLL cells. Vaccinating subcutaneously with PD-L1 and PD-L2 peptides mobilises cytoxic T-cells specific towards PD-L1 and PD-L2 expressing cells. In this study we investigate if the PD-L1 and PD-L2 specific responses can overcome leukemic cells in CLL.
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
- •CLL according to national guidelines (Lymphoma.dk).
- •Unmutated IGHV gene according to ERIC recommendations.(25)
- •No prior CLL directed treatment
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- •No life-threatening conditions
- •Adequate bone marrow function: Neutrophils > 1,0 x 109/l; Platelets > 100 x 109/l
- •Adequate renal function: Glomeruli filtration rate (eGFR)/1,73 m2 > 50 mL/min
- •Adequate liver function: Aspartate Aminotransferase < 100 U/L
- •For fertile 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 active malignant diseases requiring treatment.
- •Significant medical condition per investigators judgement e.g. severe Asthma or chronic obstructive lung disease (COLD), poorly regulated heart condition, insulin dependent diabetes mellitus.
- •Acute or chronic viral/bacterial infection e.g. human immunodeficiency virus (HIV), Cytomegalo virus (CMV), Epstein-barr virus (EBV), hepatitis or tuberculosis
- •Serious known allergies or earlier anaphylactic reactions.
- •Known sensibility towards Montanide ISA51
- •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%
- •Psychiatric disorders that according to the investigator could influence compliance.
- •Treatment with other experimental drugs
结局指标
主要结局
Clinical response according to IW-CLL
时间窗: 1 year
Progressive disease (PD), stable disease (SD), partial response (PR), complete response (CR) calculated on basis of changes in circulating lymphocytes and lymphnode/spleen/liver size according to criteria from the international working group on CLL (IW-CLL).
次要结局
- Grades of adverse events (AE)(1 year)
- Immune response by elispot(1 year)
研究者
Lars Møller Pedersen
Chief Phycisian
Herlev Hospital