Therapeutic Efficacy of Wilms Tumor Gene (WT1) MRNA-electroporated Autologous Dendritic Cell Vaccination in Patients with Myeloid Malignancies and Multiple Myeloma: a Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Immunogenicity of WT1 mRNA-transfected DC vaccination
研究概览
简要总结
Dendritic cell therapy is a promising strategy for adjuvant cancer therapy in the setting of minimal residual disease (MRD) to fight off cancer relapse and/or progression. The investigators already performed a phase I safety study in leukemia patients that were in complete remission demonstrating the absence of side effects and feasibility of the therapy. Here, the investigators want to extend on this strategy by studying the clinical efficacy of autologous DC vaccination in patients with acute and chronic myeloid leukemia and myeloma patients. Effects of DC therapy on the immune reactivity towards leukemia cells as well as clinical parameters such molecular MRD monitoring, time to relapse (TTR), progression-free survival (PFS) and overall survival(OS) will be studied in vaccinated and non-vaccinated (control) patients. Patients will be vaccinated using their own dendritic cells electroporated with mRNA coding for the full-length Wilms' tumor antigen WT1.
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
- •Acute Myeloid Leukemia (AML): all FAB subtypes except M
- •Extent of disease:
- •clinical remission after at least one course of polychemotherapy
- •high risk of relapse due to age (> 60 years) or poor risk cytogenetic/molecular markers or hyperleukocytosis at presentation or previous relapse
- •Chronic myeloid leukemia (CML): patients in chronic phase under therapy with tyrosinase kinase inhibitors who have sub-optimal response or failure and who are not eligible for hematopoietic stem cell transplantation.
- •Multiple Myeloma (MM): symptomatic with active disease, independent of earlier and/or concomitant treatment:
- •Presence of serum/urine M protein (> 3 g/dl)
- •Bone marrow plasmacytosis (>10-30%)
- •Anemia, renal failure, hypercalcemia, and/or lytic bone lesions
- •Overexpression of WT1 RNA in peripheral blood and or bone marrow as assessed by quantitative RT-PCR at the time of presentation.For CML: residual molecular disease as demonstrated by BCR-ABL RT-PCR
- •Prior treatments: Patients must have received at least one prior antileukemic chemotherapeutic regimen and must be more than 1 month past the last treatment.
- •Age: ≥ 18 years
- •Performance status: WHO PS grade 0-1 (Appendix B)
- •Objectively assessable parameters of life expectancy: more than 3 months
- •Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV
- •No concomitant use of immunosuppressive drugs
- •adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal
- •absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- •Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation
排除标准
- •Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix)
- •Subjects who are pregnant
- •Subjects who have sensitivity to drugs that provide local anesthesia
- •Subjects needing corticosteroids 1 mg/kg during vaccination; corticosteroids are allowed as part of their treatment when taken ≥ 30 days before the start of vaccination.
研究组 & 干预措施
standard therapy + vaccination
干预措施: dendritic cell vaccination (active specific immunotherapy) (Biological)
结局指标
主要结局
Immunogenicity of WT1 mRNA-transfected DC vaccination
时间窗: Upon completion of blood sample collection (before start of the vaccination at week 0 and 8 weeks after start of the vaccination) and skin biopsy collection (8 weeks after start of the vaccination) for all included patients
Induction/maintenance of molecular remission as evidenced by molecular MRD monitoring of WT1 (AML, CML and MM) and BCR/ABL RNA (CML) copies in peripheral blood
时间窗: Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination
次要结局
- Time to relapse (TTR)(Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination)
- progression-free survival(Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination)
- overall survival (OS)(Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination)
研究者
Zwi Berneman
Professor Dr. Zwi Berneman
University Hospital, Antwerp