A Phase II Trial Investigating the Benefit of Immunotherapy With Durvalumab After Autologous Transplant in High-risk Diffuse-large B-cell Lymphomas (the IDA-D Trial)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Progression-free survival
研究概览
简要总结
The trial assess the progression-free survival (PFS) two years after autologous stem cell transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1 inhibition with durvalumab.
详细描述
Background and Rationale:
Autologous stem cell transplantation (ASCT) is standard of care in the treatment concept of adult patients with multiple myeloma (MM), malignant lymphomas (including diffuse large B-cell lymphomas (DLBCL), mantle cell lymphomas, follicular lymphomas or T-cell lymphomas), acute myeloid leukemia (AML) and relapsing germ cell tumors. The number of patients treated with ASCT is steadily increasing, e.g. by +17% alone in Switzerland in the year 2015, to a total of 464 ASCT per year in Switzerland. The Inselspital (University Hospital) in Berne is the leading hospital in Switzerland for ASCT, with 145 ASCT in the year 2015. Among these 145 transplants, 31 patients had DLBCL.
The goal of treatment in DLBCL is definite cure. In DLBCL, the addition of anti-CD20 treatment to standard CHOP (Cyclophosphamid, Doxorubicin, Vincristine, Prednisone) chemotherapy has improved the cure rate after R-CHOP (Rituximab-CHOP) first-line treatment. Nevertheless, the disease is relapsing in roughly 20% of these patients. At relapse, patients are treated with salvage chemotherapy such as the R-DHAP (Rituximab, Dexamethasone, Cisplatin,Cytarabine), or R-ICE (Rituximab,Ifosfamide, Carboplatin, Etoposide) regimens, followed by BEAM (BCNU, Etoposide, Cytarabine, Melphalan) or BeEAM (Bendamustin, Etoposide, Cyclophosphamide, Melphalan) high-dose chemotherapy supported with ASCT. The overall survival rate at the Inselspital Bern and elsewhere at two years for DLBCL patients after ASCT is 60%, and, therefore, improving outcome of such patients remains an unmet clinical need. This is particularly true in high-risk DLBCL patients, such as in DLBCL patients relapsing within 12 months after first-line treatment as well as in DLBCL patients not achieving a (first or second) complete remission (CR) after induction treatment before ASCT. PFS at two years for such high-risk lymphoma patients is 50% at the investigators' institution.
Immunotherapy (such as with PD-L1 inhibition) after ASCT is a promising approach to potentially improve results after ASCT. A first study applying PD-1 inhibition with three applications (every 42 days) of Pidilizumab started between days 30 and 90 after ASCT showed a promising progression-free survival rate of 72% in relapsing DLBCL patients at 16 months after the first Pidilizumab application. These data suggest that immunotherapy after ASCT has the potential to a meaningful improvement of survival rates in DLBCL patients after ASCT.
Objective:
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with any types of DLBCL (de novo or transformed), including double-hit lymphomas, grey zone lymphomas, double or triple expressor lymphomas, unclassifiable aggressive lymphoma types or aggressive lymphomas.
- •Lymphoma patients (as listed above) in first remission considered as high-risk and defined as lymphoma patients not achieving a complete first remission after induction treatment before subsequent ASCT; or patients in second remission considered as high-risk and defined as lymphoma patients relapsing within 12 months after first-line treatment or lymphoma patients not achieving a complete second remission after salvage treatment before subsequent ASCT.
- •Age 18-75 years
- •Female patients of child-bearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to study treatment, and they must implement adequate measures (hormonal treatment p.o. or i.m., intra uterine surgical devices, or latex condoms) to avoid pregnancy during study treatment and for additional 12 months.
- •Patients must have given voluntary written informed consent.
排除标准
- •Other types of malignant lymphomas
- •Previous treatment with antibodies against PD-(L)1
- •Symptomatic CNS (Central Nervous System) involvement by lymphoma
- •Active infection requiring antibiotic/antifungal treatment
- •Lack of patient cooperation to allow study treatment as outlined in this protocol
- •Pregnancy or lactating female patients
- •Major surgery less than 30 days before start of treatment
- •Contraindications and hypersensitivity to any of the active chemotherapy compounds
研究组 & 干预措施
Durvalumab
Durvalumab 1500 mg (day 1) given every 4 weeks for a total of 12 applications (1 year).
干预措施: Durvalumab (Drug)
结局指标
主要结局
Progression-free survival
时间窗: 24 months
Number of Patients with Progression-free survival (PFS) two years after autologous stem cell transplantation (ASCT) in high-risk DLBCL patients receiving PD-L1 inhibition with durvalumab.
次要结局
- Response Rate(24 months)
- Adverse Events(24 months)
- Hematologic engraftment(24 months)
- The quality of life(24 months)
- Overall Survival(24 months)