A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab Combination (BeGeRN) in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- The recommended phase 2 dose (RP2D)
研究概览
简要总结
Despite the current advances in clinical oncology, the prognosis of patients with resistant diffuse large B cell lymphoma or relapse after high dose chemotherapy is dismal. Therefore there is a need for the introduction of novel treatment regimens. This phase I/II trial evaluates the safety and efficacy of combination bendamustine, gemcitabine, nivolumab and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. The safety of combination treatment will be evaluated with the determination of recommended dose schedule prior to expansion of enrollment to evaluate the antitumor activity of bendamustine, gemcitabine, rituximab, and nivolumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: Histologically confirmed diffuse large B-cell lymphoma
- •Refractory or relapsed after at least two prior lines of treatment (i.e. induction and salvage regimen) for diffuse large B-cell lymphoma.
- •Age 18-70 years old
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
- •Signed informed consent
- •No severe concurrent illness
排除标准
- •Uncontrolled bacterial or fungal infection at the time of enrollment
- •Requirement for vasopressor support at the time of enrollment
- •Karnofsky index <30%
- •Pregnancy
- •Somatic or psychiatric disorder making the patient unable to sign informed consent
- •Active or prior documented autoimmune disease requiring systemic treatment.
研究组 & 干预措施
Gemcitabine 700
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Nivolumab (Drug)
Gemcitabine 700
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Rituximab (Drug)
Gemcitabine 500
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Bendamustine hydrochloride (Drug)
Gemcitabine 500
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Gemcitabine 500 mg (Drug)
Gemcitabine 500
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Nivolumab (Drug)
Gemcitabine 500
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Rituximab (Drug)
Gemcitabine 700
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Bendamustine hydrochloride (Drug)
Gemcitabine 700
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Gemcitabine 700 mg (Drug)
Gemcitabine 1000
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Bendamustine hydrochloride (Drug)
Gemcitabine 1000
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Gemcitabine 1000 mg (Drug)
Gemcitabine 1000
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Nivolumab (Drug)
Gemcitabine 1000
Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv.
Duration of cycle 28 days
干预措施: Rituximab (Drug)
结局指标
主要结局
The recommended phase 2 dose (RP2D)
时间窗: 6 months
The recommended phase 2 dose (RP2D) of Bendamustine Hydrochloride and Gemcitabine in combination with Nivolumab and Rituximab in patients with Diffuse Large B-cell Lymphoma
Overall Response Rate (ORR)
时间窗: 12 months
Overall response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by LYRIC criteria and duration of response.
次要结局
- Overall Survival (OS)(12 months)
- Duration of Response (DOR)(12 months)
- Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03(12 months)
- Progression-Free Survival (PFS)(12 months)
研究者
Ivan S Moiseev
Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation
St. Petersburg State Pavlov Medical University