A Two-Stage Phase III, International, Multi-Center, Randomized, Controlled, Open-Label Study to Investigate the Pharmacokinetics, Efficacy and Safety of Rituximab SC in Combination With CHOP or CVP Versus Rituximab IV in Combination With CHOP or CVP in Patients With Previously Untreated Follicular Lymphoma Followed by Maintenance Treatment With Either Rituximab SC or Rituximab IV
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 410
- 试验地点
- 152
- 主要终点
- Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab
研究概览
简要总结
This two-stage, multi-center, randomized, controlled, open-label study will investigate the pharmacokinetics, efficacy and safety of rituximab SC versus rituximab IV in participants with previously untreated follicular non-Hodgkin's lymphoma. Participants will be randomized to receive 375 milligrams per meter square (mg/m^2) rituximab as IV infusion or 1400 milligrams (mg) rituximab SC. In addition, participants will receive standard chemotherapy. Participants who achieved a complete or partial response (PR) after 8 treatment cycles, will receive maintenance treatment for a further maximum number of 12 cycles. Maintenance treatment cycles will be repeated every 8 weeks. This is a two-stage study. Stage 1 was designed to confirm the chosen rituximab SC dose resulting in comparable rituximab serum Ctrough levels compared with rituximab IV, when given as part of induction treatment every 3 weeks. Enrollment for Stage 2 started after the rituximab SC dose was established in Stage 1. Stage 2 aimed to further investigate the efficacy and safety of rituximab SC compared with rituximab IV. The anticipated time on study treatment is 96 weeks.
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
- •Cluster of differentiation 20 (CD20)-positive, follicular Non-Hodgkin's lymphoma grade 1, 2, 3a. A tumor biopsy must have been performed within 6 months before study entry with material available for central review
- •No prior treatment
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
排除标准
- •Grade 3b follicular lymphoma
- •Transformation to high-grade lymphoma secondary to follicular lymphoma
- •Types of Non-Hodgkin's lymphoma other than follicular lymphoma
- •Presence or history of central nervous system (CNS) disease
- •Corticoid therapy during the last 4 weeks, except prednisone treatment less than (<) 20 milligrams per day (mg per day)
- •Known active bacterial, viral, fungal, or mycobacterial, or any major episode of infections requiring hospitalization or treatment with IV antibiotics within 4 weeks of start of study medication, or oral antibiotics within 2 weeks prior to start of study medication
研究组 & 干预措施
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
干预措施: Rituximab IV (Drug)
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
干预措施: Cyclophosphamide (Drug)
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
干预措施: Doxorubicin (Drug)
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
干预措施: Vincristine (Drug)
Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
干预措施: Prednisone/Prednisolone (Drug)
Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
干预措施: Rituximab SC (Drug)
Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
干预措施: Cyclophosphamide (Drug)
Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
干预措施: Doxorubicin (Drug)
Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
干预措施: Vincristine (Drug)
Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
干预措施: Prednisone/Prednisolone (Drug)
结局指标
主要结局
Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab
时间窗: Stage I: Cycle (Cy) 7 Day (D) 21 (within 2 hours predose on Cy8) of induction treatment (1 Cy=3 weeks)
Stage II: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for Non-Hodgkin Lymphoma (NHL)
时间窗: Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Overall Response comprised complete response (CR), CR unconfirmed (CRu), or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and computed tomography (CT) scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by more than (\>) 75% in the sum of the products of greatest diameters (SPD); PR: Greater than or equal to (≥) 50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.
次要结局
- Stage I: Maximum Serum Concentrations (Cmax) of IV and SC Rituximab(Stage I (Induction): Predose (within 2hr) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description))
- Stage I: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL(Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks))
- Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL(Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks))
- Stage I: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL(Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks))
- Stage II: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL(Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks))
- Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL(Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks))
- Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL(Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks))
- Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL(Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks))
- Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse, New Anti-Lymphoma Treatment or Death Assessed Using International Working Group Response Criteria for NHL(Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Event-Free Survival Assessed Using International Working Group Response Criteria for NHL(Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description))
- Percentage of Participants Who Died(Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years]))
- Overall Survival (OS)(Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years]))
- Stage I: Observed Area Under the Serum Concentration-Time Curve (AUC) of Rituximab(Stage I (Induction): Predose (within 2 hour [hr]) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse or Death(Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Progression-Free Survival (PFS) Assessed Using International Working Group Response Criteria for NHL(Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Ctrough of Rituximab at Each Induction Treatment Cycle(Stage I and II (Pooled): Predose (within 2hr) up to data cutoff of 31 Oct 2013 [up to 32 months]) (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Ctrough of Rituximab at Each Maintenance Treatment Cycle(Stage I and II (maintenance): Predose (within 2hr) up to data cutoff of 11 Jan 2016 [up to 6 years]) (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Rituximab Levels 12 Weeks, 24 Weeks, and 36 Weeks After the Last Rituximab Administration(12 weeks, 24 weeks, and 36 weeks after the last rituximab administration (up to data cutoff of 11 Jan 2016 [up to 6 years]))
- Percentage of Participants With B-Cell Depletion by Cycle for Induction Phase(Stage I and II (induction): for rituximab IV - D1 of Cy 1 to 8 (1 Cy=3 weeks); for rituximab SC - D1 of Cy 1 and Cy 3 to 8, D0 of Cy 2)
- Percentage of Participants With B-Cell Depletion by Cycle for Maintenance Phase(Stage I and II (maintenance): D1 of Cy 9 to 20 (1 Cy=8 weeks) (up to data cutoff of 11 Jan 2016 [up to 6 years]))
- Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Chimeric Antibodies (HACAs) to Rituximab(Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Human Antibodies (HAHAs) to Rituximab(Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description))
- Stage I and II (Pooled): Percentage of Responses Showing Time Saved of Staff as Per Physician/Nurse Opinions With Each Administration of Rituximab SC as Compared to Rituximab IV at the End of Cy 8, 15 and 20(After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20))
- Percentage of Responses Who Showed Rituximab SC Formulation Convenient as Compared to Rituximab IV Formulation as Assessed by Physician/Nurse Opinion(After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20))