A Phase II Comparative, Open-Label, Randomized, Multicenter, China-Only Study to Investigate the Pharmacokinetics, Efficacy and Safety of Subcutaneous Rituximab Versus Intravenous Rituximab Both in Combination With CHOP in Previously Untreated Patients With CD20 Positive Diffuse Large B Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 8
- 主要终点
- Subcutaneous Serum Rituximab Trough Concentration (Ctrough SC) and Intravenous Serum Rituximab Trough Concentration (Ctrough IV)
研究概览
简要总结
This is a multicenter China-only study to investigate the PK, efficacy and safety of SC rituximab versus IV rituximab, both in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in previously untreated participants with CD20 positive DLBCL. Participants will be randomized to receive eight cycles of rituximab SC or rituximab IV combined with six or eight cycles of standard CHOP chemotherapy. After the end of study treatment, participants will be followed-up every 3 months for 6 months.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Previously untreated CD20 positive diffuse large B-cell lymphoma (DLBCL)
- •Participants with an International Prognostic Index (IPI) score of 1 to 5 or IPI score of 0 with bulky disease, defined as one lesion >/=7.5 cm
- •At least one bi-dimensionally measurable lesion defined as >/=1.5 cm in its largest dimension on CT scan
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Left ventricular ejection fraction (LVEF) >/=50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram
- •A negative serum pregnancy test or a negative urine pregnancy test within 7 days prior to study treatment
- •For men who are not surgically sterile, agreement to use a barrier method of contraception during the treatment period and until >/=12 months after the last dose of rituximab SC or rituximab IV or according to institutional guidelines for CHOP chemotherapy, whichever is longer, and agreement to request that their partners use an additional method of contraception
- •For women of reproductive potential who are not surgically sterile, agreement to use adequate methods of contraception during the treatment period and until >/=12 months after the last dose of rituximab SC or rituximab IV or according to institutional guidelines for CHOP chemotherapy, whichever is longer
- •Adequate hematologic function confirmed within 14 days prior to randomization
排除标准
- •Transformed non-Hodgkin's lymphoma (NHL) or types of NHL other than DLBCL and its subtypes according to World Health Organization classification
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- •Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
- •Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation or surgery for diagnosis
- •Prior treatment with cytotoxic drugs or rituximab for another condition (e.g.,rheumatoid arthritis) or prior use of an anti-CD20 antibody
- •Current or recent treatment with another investigational drug or participation in another investigational therapeutic study
- •Ongoing corticosteroid use (>30 mg/day of prednisone or equivalent)
- •Primary CNS lymphoma, blastic variant of mantle cell lymphoma, or histologic evidence of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, and primary cutaneous DLBCL
- •History of other malignancy that could affect compliance with the protocol or interpretation of results
- •Evidence of significant, uncontrolled concomitant diseases including but not limited to significant cardiovascular disease or pulmonary disease
- •Any of the following abnormal laboratory values: creatinine >1.5 upper limit of normal (ULN), aspartate aminotransferase (AST) / alanine aminotransferase (ALT) >2.5ULN, total bilirubin >1.5ULN, prothrombin time - international normalized ratio (PT-INR) / partial thromboplastin time (PTT) / activated partial thromboplastin time (aPTT)>1.5ULN
- •Positive test results for chronic hepatitis B (HBV) and or hepatitis C (HCV) infection; Participants with occult or prior HBV infection (defined as negative HBsAg and positive total hepatitis B core antibody [HBcAb]) may be included if HBV DNA is undetectable; Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
- •Known history of human immunodeficiency virus (HIV)
研究组 & 干预措施
Rituximab IV+CHOP
Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Rituximab IV (Drug)
Rituximab IV+CHOP
Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Cyclophosphamide (Drug)
Rituximab IV+CHOP
Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Doxorubicin (Drug)
Rituximab IV+CHOP
Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Vincristine (Drug)
Rituximab IV+CHOP
Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Prednisone (Drug)
Rituximab IV+CHOP
Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Paracetamol (Drug)
Rituximab IV+CHOP
Participants will receive 8 cycles of IV rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Diphenhydramine hydrochloride or alternative antihistamine (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Rituximab SC (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Rituximab IV (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Cyclophosphamide (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Doxorubicin (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Vincristine (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Prednisone (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Paracetamol (Drug)
Rituximab SC+CHOP
Participants will receive 1 cycle of IV plus 7 cycles of SC rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
干预措施: Diphenhydramine hydrochloride or alternative antihistamine (Drug)
结局指标
主要结局
Subcutaneous Serum Rituximab Trough Concentration (Ctrough SC) and Intravenous Serum Rituximab Trough Concentration (Ctrough IV)
时间窗: At Cycle 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks
For this pharmacokinetics (PK) primary outcome measure the serum rituximab Ctrough for SC and IV administrations were measured at Cycle 7, 21 days after study treatment administration for Cycle 7 (pre-dose of Cycle 8). Geometric mean ratio and 90% confidence interval were estimated based on an ANCOVA model adjusted for tumor load at baseline and are reported in the statistical analysis.
次要结局
- CRR, as Determined by the Investigator Using Lugano Response Criteria for Malignant Lymphoma(6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks))
- Maximum Observed Serum Concentration (Cmax) of Rituximab(At Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks)
- Area Under the Curve (AUC) of Rituximab(During Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks)
- Number of Participants With Rituximab Administration-related Reactions (ARRs)(Up to 24 hours after the last dose of study treatment (up to approximately 24 weeks))
- Observed SC and IV Rituximab Area Under the Curve (AUCsc and AUCiv)(During Cycle 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks)
- Time to Cmax (Tmax) of Rituximab(At Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks)
- Trough Serum Concentration (Ctrough) of Rituximab(At Cycles 2 and 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks)
- CRR, as Determined by IRC Using International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) 1999 Guidelines(6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(AEs were reported up to 28 days after the last dose (up to approximately 7 months), and SAEs were reported up to 6 months after the last dose of study treatment (up to approximately 1 year))
- Number of Participants Positive for Anti-drug Antibodies (ADAs) to Rituximab(From baseline up to 6 months after the last dose of study treatment (up to approximately 1 year))
- Complete Response Rate (CRR) as Determined by the Independent Review Committee (IRC) Using Lugano Response Criteria (LRC) for Malignant Lymphoma(6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks))
- Objective Response Rate (ORR), Complete Response (CR) or Partial Response (PR), as Determined by Investigator and IRC Using Lugano Response Criteria (LRC) for Malignant Lymphoma(6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks))
- Number of Participants Positive for Anti-rHuPH20 Antibodies(From baseline up to 6 months after the last dose of study treatment (up to approximately 1 year))