Improvement of Outcome in Elderly Patients or Patients Not Eligible for High-dose Chemotherapy With Aggressive NHL in First Relapse/Progression by Adding Nivolumab to Gemcitabine, Oxaliplatin Plus Rituximab in Case of B-cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 348
- 试验地点
- 76
- 主要终点
- PFS
研究概览
简要总结
This study evaluates the addition of nivolumab to gemcitabine, oxaliplatin plus rituximab in case of B-cell lymphoma
详细描述
International, multicentre, randomised, open-label, treatment optimisation study, preceded by safety run-in phases conducted for B-cell and T-cell lymphoma separately.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •patients with first relapse or progression of an aggressive Non-Hodgkin's lymphoma
- •all patient >65 years of age or > 18 years if not eligible for neither autologous nor allogeneic stem cell transplantation
- •all patient >65 years of age or older than 18 years if HCT-CI score > 2 or patients who underwent prior autologous stem cell transplantation and are not eligible for allogeneic stem cell Transplantation
- •All risk groups (IPI 0 to 5)
- •Diagnosis of aggressive Non-Hodgkin's lymphoma, based on an excisional biopsy of a lymph node or on an appropriate sample of a lymph node or of an extranodal involvement at initial diagnosis or relapse or Progression. The entities treated in the study will be based on the WHO 2017 classification.
- •ECOG 0 - 2
- •only one prior chemotherapy regimen including an anthracycline. The last cytotoxic drug must be given at least four weeks before entering the study. Rituximab must be part of the first-line regimen in case of B-cell lymphoma (except for primary CD20- negative lymphoma). Patients may have received prior radiation therapy as part of their first-line therapy
- •Men who are sexually active with women of childbearing potential (WOCBP) must not father a child during and up to 6 months after GemOx and up to 12 months after Rituximab and/or Nivolumab. They are advised to do cryoconservation of sperm prior to treatment.
- •Written informed consent of the patient
- •Patient must be covered by social security system
排除标准
- •Already initiated lymphoma therapy after first relapse or progression
- •Serious accompanying disorder or impaired organ function
- •WBC < 2.5 G/l, Neutrophils < 2 G/l, Platelets < 100 G/l
- •Prolongation of QTc interval > 450 ms, demonstrated in one electrocardiogram (done as triplicate). This does not apply for patients with a block of the right and/or left bundle branch.
- •Family history for Long QT-Syndrome
- •active, known or suspected autoimmune disease
- •no requirement for immunosuppressive doses of systemic corticosteroids
- •Chronic active hepatitis B or C
- •HIV-infection
- •Patients with a severe immunodeficiency
- •Previous therapy with Nivolumab,Gemcitabine or Oxaliplatin
- •Patients with a "currently active" second malignancy other than non-melanoma skin cancer
- •CNS involvement of lymphoma
- •Persistent neuropathy grade >2
- •Pregnancy or breast-feeding women
- •Women of childbearing potential
- •Active serious infections not controlled by oral and/or intravenous antibiotics or anti-fungal medication
- •Any medical condition which in the opinion of the investigator places the subject at an unacceptably high risk for toxicities
- •Lymphomas other than those listed in the inclusion criteria notably indolent lymphoma, Mantle cell lymphoma, Burkitt lymphoma, adult T-cell leukemia/lymphoma.
- •Persons not able to understand the impact, nature, risks and consequences of the trial (including language barrier)
- •Persons not agreeing to the transmission of their pseudonymous data
- •Persons depending on sponsor or investigator
- •Persons from highly protected Groups
- •Allergies and Adverse Drug Reaction History to study drug components
- •Participation in another clinical trial with drug intervention within 4 weeks prior to start of the first cycle and during the study. However, participation in a clinical trial of firstline therapy of lymphoma is allowed.
研究组 & 干预措施
(R)-GemOx
eight cycles of (R)-GemOx (Gemcitabine 1000 mg/m2, d1, Oxaliplatin 100 mg/m2, d1, Rituximab 375 mg/m2 in case of B-cell lymphoma disease, repeated every 2 wks)
干预措施: Rituximab (Drug)
(R)-GemOx
eight cycles of (R)-GemOx (Gemcitabine 1000 mg/m2, d1, Oxaliplatin 100 mg/m2, d1, Rituximab 375 mg/m2 in case of B-cell lymphoma disease, repeated every 2 wks)
干预措施: Gemcitabine (Drug)
(R)-GemOx
eight cycles of (R)-GemOx (Gemcitabine 1000 mg/m2, d1, Oxaliplatin 100 mg/m2, d1, Rituximab 375 mg/m2 in case of B-cell lymphoma disease, repeated every 2 wks)
干预措施: Oxaliplatin (Device)
Nivo-(R)-GemOx
eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
干预措施: Nivolumab (Drug)
Nivo-(R)-GemOx
eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
干预措施: Rituximab (Drug)
Nivo-(R)-GemOx
eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
干预措施: Gemcitabine (Drug)
Nivo-(R)-GemOx
eight cycles of nivolumab (240 mg flatdose) plus (R)-GemOx in 2-wk intervals followed by additional 9 infusions of Nivolumab (480 mg flatdose) in 4-wk intervals as consolidation or up to progression or unacceptable toxicity, whatever occurs first
干预措施: Oxaliplatin (Device)
结局指标
主要结局
PFS
时间窗: 1 year
Progression free survival
次要结局
- Primary Progression rate(up to 2 years after inclusion of last patient)
- Biological Parameters according to 9p24.1 alterations(up to 2 years after inclusion of last patient)
- Relapse rate(up to 2 years after inclusion of last patient)
- EFS(up to 2 years after inclusion of last patient)
- Protocol adherence according to cumulative dose of immunochemotherapy given(up to 2 years after inclusion of last patient)
- QoL(up to 1 year after inclusion of last patient)
- PR rate(4-6 weeks after cycle 8 (each cycle is 14 days))
- ORR rate(4-6 weeks after cycle 8 (each cycle is 14 days))
- Duration of response(up to 2 years after inclusion of last patient)
- Treatment related deaths rate(up to 2 years after inclusion of last patient)
- Toxicities: rates and grades of adverse events(up to 2 years after inclusion of last patient)
- Protocol adherence according to duration of given chemotherapy cycles(up to 2 years after inclusion of last patient)
- CR rate(4-6 weeks after cycle 8 (each cycle is 14 days))
- OS(up to 2 years after inclusion of last patient)
- Protocol adherence according to number of given chemotherapy cycles(up to 2 years after inclusion of last patient)
- Biological Parameters according to PD-L1 expression alterations(up to 2 years after inclusion of last patient)
- Biological Parameters according to PD-1 expression(up to 2 years after inclusion of last patient)
- Biological Parameters according to cell of origin(up to 2 years after inclusion of last patient)
- Protocol adherence according to relative dose of immunochemotherapy given(up to 2 years after inclusion of last patient)