NCT03850522终止2 期
Phase IIa Trial of PD-L1 Peptide Vaccination as Monotherapy in High Risk Smoldering Multiple Myeloma
Lene Meldgaard Knudsen2 个研究点 分布在 1 个国家目标入组 6 人开始时间: 2019年2月18日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Overall response rate
研究概览
简要总结
This study is evaluating a new vaccine against PD-L1 as a possible treatment for high-risk smoldering multiple myeloma.
详细描述
Smoldering multiple myeloma is an asymptomatic disorder with an annual risk of 10% of progression to the incurable cancer multiple myeloma. While many patients live for many years without progression, high risk patients have a median risk of progression of 29 months. No therapy has been approved for this indication. New treatments with limited adverse events are in high demand for this unmet medical need. An effective peptide vaccine would represent an ideal candidate, since vaccines generally have very low levels of side effects.
This study will explore if vaccination against the immune checkpoint molecule PD-L1 leads to responses in patients with high risk smoldering myeloma. PD-L1 is thought to play a role in the rate of progression from smoldering myeloma to symptomatic myeloma. Targeting this pathway with little risk of adverse events would potentially prevent or delay progression to symptomatic myeloma.
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
- •Patient has confirmed SMM according to a definition derived from the International Myeloma Working Group (IMWG) definition (International Working Group, 2003)
- •Serum M-component >30g/L and/or
- •Urine M-component ≥ 500mg/24 hours and/or
- •≥10% clonal plasma cells in bone marrow
- •and no CRAB criteria or myeloma defining events (see exclusion criteria)
- •High risk of progression to symptomatic multiple myeloma defined by the presence of ≥ 2 of the risk factors below:
- •Bone marrow Plasma Cells (BMPCs) ≥ 20%
- •M-component > 2g/dL
- •FLC ratio > 20
- •Age ≥18 years
- •Performance status ≤ 2 (ECOG-scale)
- •Expected survival > 3 months
- •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.
- •The accepted contraceptive methods are
- •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation. Oral, intravaginal or transdermal.
- •Progestogen-only hormonal contraception associated with inhibition of ovulation. Oral, injectable, implantable.
- •Intrauterine device (IUD)
- •Intrauterine hormone-releasing system (IUS)
- •Bilateral tubal occlusion
- •Vasectomized partner
- •Sexual abstinence
排除标准
- •Non-secretory myeloma
- •Patients fulfilling CRAB criteria:
- •i. C: Hypercalcemia,
- •s-Ca-ion >1,40 mmol/L, attributable to myeloma ii. R: Renal failure
- •Estimated or measured creatinine clearance <40ml/min, attributable to myeloma
- •Increased s-creatinine, attributable to myeloma
- •Decrease in estimated or measured creatinine clearance <35% within a year, attributable to myeloma
- •Renal biopsy-verified renal changes attributable to myeloma iii. A: Anemia, Hgb < 6,3mmol/L (10g/dl), attributable to myeloma iv. B: Bone lesions on X-ray, CT or PET-CT
- •Evidence of myeloma defining events i. Clonal bone marrow plasma cell percentage ≥ 60% ii. Ratio of involved/uninvolved serum free light chain ratio ≥ 100 iii. >1 focal lesions on MRI studies, if clinically indicated
- •Plasma cell leukemia
- •Signs of amyloidosis
- •Other malignancies in the medical history excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer and patients cured for another malignant disease with no sign of relapse two 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
- •Concurrent treatment with other anti-cancer drugs.
结局指标
主要结局
Overall response rate
时间窗: Planned analysis cut-off per patient: two weeks after last vaccination.
Overall response rates (ORR) defined by IMWG criteria as PR+VGPR+CR+sCR during treatment and two weeks after end of treatment per patient.
次要结局
- Overall survival (OS)(Planned analysis 2 years and 5 years post initiation of therapy.)
- Time to progression (TTP)(Planned analysis 2 years and 5 years post initiation of therapy.)
- Immunogenicity of the PD-L1 vaccine(Samples taken before, during and two weeks after last vaccination.)
- Incidence of Treatment Emergent Adverse Events(Planned analysis cut-off per patient: two weeks after last vaccination)
- Progression-free survival (PFS)(Planned analysis 2 years and 5 years post initiation of therapy.)
研究者
Lene Meldgaard Knudsen
Head of Department, Department of Hematology
Herlev Hospital
研究点 (2)
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