A Study of the Radiotherapy Followed by Tiselizumab Combined With RCHOP in the Frontline Treatment of Follicular Lymphoma Patients With Bulky Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Best Complete response (CR) rate
研究概览
简要总结
This was a single center, single arm, phase II study. Patients with previously untreated follicular lymphoma were enrolled from the department of lymphoma, Tianjin Medical University Cancer Institute and Hospital. The bulky disease was received radiation (dose:18～24Gy) before RCHOP. Patients began chemoimmunotherapy 1～2 weeks later than radiation. Treatment included Tiselizumab (200 mg iv d1) plus R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles. Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years. Response was assessed by PET/CT scan after cycle 4 and cycle 6.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed CD20 positive (+) follicular lymphoma, grade 1, 2, or 3a，bulky disease (Mass diameter ≥ 7 cm)
- •Have had no prior systemic treatment for lymphoma
- •Meeting Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria for initiation of treatment
- •Age 18-75 years
- •ECOG Performance Status of 0-2 .Stage II, III, or IV by Ann Arbor staging system.
- •Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.
- •Hematological: WBC≥3.5×109/L, Platelets ≥ 75×109/L,Absolute Neutrophil Count (ANC) ≥ 1.0×109/L，Hemoglobin (Hgb) ≥ 80 g/L
- •Renal: Calculated creatinine clearance ≥ 50 mL/min
- •Hepatic: Bilirubin ≤ 1.5 × upper limit of normal (ULN), AST/ALT ≤ 2.5×ULN
- •Females of childbearing potential must be willing to abstain from vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study and for 6 months after the last dose of study drug(s). Males able to father a child must be willing to abstain
- •Life expectancy ≥6 months
- •Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
排除标准
- •Known active central nervous system lymphoma or leptomeningeal disease,
- •Evidence of diffuse large B-cell transformation
- •Grade 3b FL
- •Concurrent malignancy or malignancy within the last 3 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ) whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial
- •Known history of human immunodeficiency virus (HIV), or active hepatitis C Virus, or active hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed John Cunningham (JC) virus infection，any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association functional classification. Or left ventricular ejection fraction <50%;
- •Known history of human immunodeficiency virus (HIV), or active hepatitis C Virus, or active hepatitis B Virus infection, or any uncontrolled active significant infection
- •Known pneumonia associated with idiopathic pulmonary fibrosis, machine (for example, occlusive bronchiolitis), history of drug induced pneumonia, or screening during the chest computed tomography (CT) showed active pneumonia
- •Have serious neurological or psychiatric history, can't normal study, including dementia, epilepsy, severe depression and mania
- •Patients who were deemed by the investigator to be ineligible for enrollment
研究组 & 干预措施
Experimental: Treatment arm
Radiation (dose:18～24Gy) ，chemoimmunotherapy 1～2 weeks later than radiation. Tiselizumab (200 mg iv d1) R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles.
Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years.
干预措施: radiation therapy (Radiation)
Experimental: Treatment arm
Radiation (dose:18～24Gy) ，chemoimmunotherapy 1～2 weeks later than radiation. Tiselizumab (200 mg iv d1) R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles.
Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years.
干预措施: Tiselizumab (Drug)
Experimental: Treatment arm
Radiation (dose:18～24Gy) ，chemoimmunotherapy 1～2 weeks later than radiation. Tiselizumab (200 mg iv d1) R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles.
Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years.
干预措施: Rituximab (Drug)
Experimental: Treatment arm
Radiation (dose:18～24Gy) ，chemoimmunotherapy 1～2 weeks later than radiation. Tiselizumab (200 mg iv d1) R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles.
Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years.
干预措施: Cyclophosphamide (Drug)
Experimental: Treatment arm
Radiation (dose:18～24Gy) ，chemoimmunotherapy 1～2 weeks later than radiation. Tiselizumab (200 mg iv d1) R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles.
Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years.
干预措施: Doxorubicin (Drug)
Experimental: Treatment arm
Radiation (dose:18～24Gy) ，chemoimmunotherapy 1～2 weeks later than radiation. Tiselizumab (200 mg iv d1) R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles.
Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years.
干预措施: Vincristine (Drug)
Experimental: Treatment arm
Radiation (dose:18～24Gy) ，chemoimmunotherapy 1～2 weeks later than radiation. Tiselizumab (200 mg iv d1) R-CHOP (rituximab 375 mg/m2 intravenous [IV] day 2, cyclophosphamide 750 mg/m2 IV day 3, doxorubicin 50 mg/m2 IV day 3, vincristine 1.4 mg/m2 [maximum 2.0 mg total] IV day 3, and prednisone 100 mg oral days 3-7, 21～28 days for one cycle ) for six cycles.
Rituximab was given every 2 months to patients who were complete metabolic response /partial metabolic response（CMR/PMR）after first-line chemo until 2 years.
干预措施: Prednisone (Drug)
结局指标
主要结局
Best Complete response (CR) rate
时间窗: Through completion of treatment (estimated to be 2.5 year)
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria
次要结局
- Best overall response rate (ORR)(Through completion of treatment (estimated to be 2.5 year))
- 2 year progression-free survival(From date of patients sign informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years)
- Percentage of Participants With Adverse Events(Up to 30 days after completion of study treatment)