A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 289
- 试验地点
- 226
- 主要终点
- 1-year Post-induction Disease-free Survival (DFS) Rate
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bendamustine hydrochloride and rituximab together alone is more effective than giving bendamustine hydrochloride and rituximab together with bortezomib or lenalidomide in treating follicular lymphoma.
PURPOSE: This randomized phase II trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage II, stage III, or stage IV follicular lymphoma.
详细描述
OBJECTIVES:
Primary
- To compare the complete remission rate in patients with high-risk follicular lymphoma receiving induction therapy comprising bendamustine hydrochloride and rituximab with vs without bortezomib.
- To compare the 1-year post-induction disease-free survival rate in patients receiving continuation therapy comprising rituximab with vs without lenalidomide.
Secondary
- To determine the 3-year progression-free survival and the 5-year overall survival of these patients.
- To evaluate patient-reported outcomes at baseline and during treatment to determine differences in symptom palliation, treatment-related symptoms, and overall health-related quality of life.
- To examine the association between baseline Follicular Lymphoma International Prognostic Index (FLIPI) information and outcome of these patients.
- To examine the association between baseline and end-of-treatment patient comorbidities assessed by the Cumulative Illness Rating Scale (CIRS) and outcome.
- To create an image and tissue bank including serial PET/CT scans, diagnostic paraffin-embedded tissue, germline DNA, and serial blood and bone marrow samples sufficient to support proposed and future studies of tumor and host characteristics that may predict for clinical outcome, including treatment arm effects, and enhance existing prognostic indices. (exploratory)
- To evaluate the rate of peripheral neuropathy associated with subcutaneous and intravenous bortezomib.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A then Arm D (Induction with Bendamustine + Rituximab; Continuation with Rituximab)
Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: rituximab (Biological)
Arm A then Arm D (Induction with Bendamustine + Rituximab; Continuation with Rituximab)
Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Bendamustin (Drug)
Arm B then Arm E (Induction with Bendamustine + Rituximab + Bortezomib; Continuation with Rituximab)
Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.
干预措施: rituximab (Biological)
Arm B then Arm E (Induction with Bendamustine + Rituximab + Bortezomib; Continuation with Rituximab)
Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.
干预措施: Bendamustin (Drug)
Arm B then Arm E (Induction with Bendamustine + Rituximab + Bortezomib; Continuation with Rituximab)
Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.
干预措施: bortezomib (Drug)
Arm C then Arm F (Induction with Bendamustine+Rituximab; Continuation with Lenalidomide + Rituximab)
Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: rituximab (Biological)
Arm C then Arm F (Induction with Bendamustine+Rituximab; Continuation with Lenalidomide + Rituximab)
Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Bendamustin (Drug)
Arm C then Arm F (Induction with Bendamustine+Rituximab; Continuation with Lenalidomide + Rituximab)
Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: lenalidomide (Drug)
结局指标
主要结局
1-year Post-induction Disease-free Survival (DFS) Rate
时间窗: Assessed at 1 year post-induction, approximately 1.5 years
1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion. The purpose of this analysis is to compare the 1-year post-induction disease-free survival (DFS) rate with rituximab plus lenalidomide to rituximab alone as continuation therapy following induction treatment of bendamustine+rituximab, therefore, patients with induction treatment of bendamustine + rituximab + bortezomib were not included in this analysis.
Complete Remission (CR) Rate
时间窗: Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years
Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy. This analysis was conducted among 222 evaluable patients for the primary analysis. The purpose of this analysis is to compare the complete remission rate of rituximab + bendamustine vs. bortezomib + rituximab + bendamustine as induction therapy, therefore, the proportion of patients with complete remission was compared between Arm B (bortezomib + rituximab + bendamustine) and Arms A and C combined (rituximab + bendamustine).
次要结局
- Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Baseline(Assessed at baseline)
- 3-year Progression-free Survival Rate(Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry)
- 5-year Overall Survival Rate(Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry)
- 1-year Disease-free Survival (DFS) Rate(Assessed at 1 year post-induction, approximately 1.5 years)
- Progression-free Survival(Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry)
- Proportion of Patients With Grade 3 or Higher Peripheral Neuropathy(Assessed every cycle during treatment and for 30 days after discontinuation of treatment, up to 15 years)
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Mid-induction Treatment(Assessed at cycle 3 or cycle 4, approximately 3 or 4 months)
- Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Mid-induction Treatment(Assessed at cycle 3, approximately 3 months)
- Complete Remission (CR) Rate(Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years)
- Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Baseline(Assessed at baseline)
- Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Mid-treatment(Assessed at cycle 3 or cycle 4, approximately 3 or 4 months)
- Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at End of Induction Treatment(Assessed at cycle 6, approximately 6 months)
- Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at End of Induction Treatment(Assessed at cycle 6, approximately 6 months)
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at End of Induction Treatment(Assessed at cycle 6, approximately 6 months)
- Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Baseline(Assessed at baseline)
- Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Mid-induction Treatment(Assessed at cycle 3 or cycle 4, approximately 3 or 4 months)
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Baseline(Assessed at baseline)
- Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at the End of Induction Treatment(Assessed at end of induction treatment (cycle 6), approximately 6 months)