A Phase III, Open-Label, Multicenter, Randomized, Study Evaluating the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab Plus Gemcitabine Plus Oxaliplatin (R-GEMOX) Versus R-GEMOX Alone in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 270
- 试验地点
- 62
- 主要终点
- Stage 1: Number of Participants With Peripheral Neuropathy (PN)
研究概览
简要总结
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial (RCT).
详细描述
The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants. The randomized controlled trial (RCT) (Stage 2) will compare Pola-R-GemOx versus R-GemOx alone using overall survival (OS). This is an event-driven trial.
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
- •Histologically-confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS) or history of transformation of indolent disease to DLBCL
- •Relapsed disease (disease that has recurred following a response that lasted ≥ 6 months from completion of the last line of therapy) or refractory disease (disease that did not respond to or that progressed during therapy or progressed within 6 months (< 6 months) of prior therapy)
- •At least one (≥ 1) line of prior systemic therapy:
- •Patients may have undergone autologous hematopoietic stem cell transplantation (HSCT) prior to recruitment; In such cases, salvage chemotherapy (e.g., rituximab, dexamethasone, cytarabine, and cisplatin [R-DHAP] and rituximab, ifosfamide, carboplatin, and etoposide phosphate [R-ICE]) will be counted as one line of therapy and conditioning chemotherapy (e.g., BEAM) followed by consolidative autologous HSCT will be counted as one line of therapy
- •Patients may have undergone allogeneic HSCT prior to recruitment, so long as they are off all immunosuppressive therapy and have no active GVHD; In such cases, salvage chemotherapy (e.g., R-DHAP and R-ICE) will be counted as one line of therapy and conditioning chemotherapy (e.g., carmustine, etoposide, cytarabine, and melphalan [BEAM]) followed by allogeneic HSCT will be counted as a separate line of therapy
- •Participants may have undergone CAR T-cell therapy prior to recruitment. In such cases, cell collection, conditioning chemotherapy, and infusion will be counted as one line of therapy.
- •Local therapies (e.g., radiotherapy) will not be considered as lines of treatment
- •For participants with a history of the transformation of indolent disease to DLBCL, it is preferred that participants have received at least one treatment for the transformed lymphoma. However, if there are cases where the participants have received an anthracycline-containing chemotherapy regimen (such as R-CHOP) for the indolent lymphoma only, then these participants can be considered as eligible.
- •At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
- •Adequate hematological function
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm,
排除标准
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
- •Contraindication to rituximab, gemcitabine or oxaliplatin
- •Peripheral neuropathy assessed to be > Grade 1 according to NCI CTCAE v5.0
- •Prior use of polatuzumab vedotin or a gemcitabine plus platinum-based agent combination, recent participation in a clinical trial, and/or treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy within 2 weeks
- •Planned autologous or allogenic stem cell transplantation or CAR T-cell therapy at time of recruitment
- •Primary or secondary central nervous system (CNS) lymphoma
- •Richter's transformation or prior CLL
- •Abnormal laboratory values or health conditions, as assessed by the investigator, any known conditions preventing adherence to protocol or active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
- •Vaccination with a live vaccine within 4 weeks prior to treatment
- •Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug
- •Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug
研究组 & 干预措施
Pola-R-GemOx (Stage 1)
Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Polatuzumab Vedotin (Drug)
Pola-R-GemOx (Stage 1)
Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Rituximab (Drug)
Pola-R-GemOx (Stage 1)
Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Gemcitabine (Drug)
Pola-R-GemOx (Stage 1)
Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Oxaliplatin (Drug)
Pola-R-GemOx (Stage 2)
Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Polatuzumab Vedotin (Drug)
Pola-R-GemOx (Stage 2)
Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Rituximab (Drug)
Pola-R-GemOx (Stage 2)
Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Gemcitabine (Drug)
Pola-R-GemOx (Stage 2)
Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Oxaliplatin (Drug)
R-GemOx (Stage 2)
Participants will receive rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Rituximab (Drug)
R-GemOx (Stage 2)
Participants will receive rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Gemcitabine (Drug)
R-GemOx (Stage 2)
Participants will receive rituximab 375 mg/m^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m^2 administered IV and oxaliplatin 100 mg/m^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Stage 1: Number of Participants With Peripheral Neuropathy (PN)
时间窗: From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (Up to approximately 8.3 months)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants receiving polatuzumab vedotin may develop PN, including peripheral sensory and/or motor neuropathy. Symptoms included hypoesthesia, hyperesthesia, paresthesia, dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, loss of balance, orthostatic hypotension, syncope, or neuropathic pain.
Stage 2: Overall Survival (OS)
时间窗: From randomization to death (Up to approximately 34 months)
OS was defined as the time from randomization to the death from any cause during the study. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization. Kaplan-Meier (KM) method was used to estimate median OS for each treatment arm.
Stage 1: Number of Participants With Adverse Events (AEs)
时间窗: From treatment initiation until 90 days after the last dose of study drug or initiation of non-protocol-specified anti-lymphoma treatment (NALT) (Up to approximately 8.3 months)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
次要结局
- Stage 1 and Stage 2: Progression-free Survival (PFS)(From randomization to first occurrence of PD or death (Up to approximately 34 months))
- Stage 2: Complete Response Rate (CRR), as Determined by an Independent Review Committee (IRC) at the End of Treatment(Up to approximately 8.5 months)
- Stage 2: Objective Response Rate (ORR) as Determined by an IRC at End of Treatment(Up to approximately 8.5 months)
- Stage 1 and Stage 2: Percentage of Participants With Best Overall Response (BOR) as Determined by the Investigator(Up to approximately 34 months)
- Stage 1 and Stage 2: CRR as Determined by the Investigator at End of Treatment(Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months)
- Stage 1 and Stage 2: ORR as Determined by the Investigator at End of Treatment(Stage 1: Up to approximately 6.2 months and Stage 2: Up to approximately 8.5 months)
- Stage 2: Duration of Response (DOR)(Up to approximately 34 months)
- Stage 1 and Stage 2: Event-free Survival (EFSeff)(Up to approximately 34 months)
- Stage 2: Time to Deterioration in Physical Functioning as Measured by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (EORTC QLQ-C30)(Up to approximately 34 months)
- Stage 2: Time to Deterioration in Fatigue Scale as Measured by the EORTC QLQ-C30(Up to approximately 34 months)
- Stage 2: Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Lymphoma Subscale (FACT-Lym LymS)(Up to approximately 34 months)
- Stage 2: Change From Baseline in Physical Functioning as Measured by EORTC QLQ-C30(Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months))
- Stage 2: Change From Baseline in Fatigue Scale as Measured by EORTC QLQ-C30(Baseline, Day 1 of Cycles 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months))
- Stage 2: Change From Baseline in FACT-Lym LYMS Scores(Baseline, Day 1 of Cycle 2, 3, 5 and 7 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months))
- Stage 2: Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item (FACT/GOG-NTX-12) Scores(Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7 and 8 (Cycle length= 21 days), end of treatment, long-term follow-up visits every two months (up to approximately 34 months))
- Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Physical Functioning Scale(Up to approximately 34 months)
- Stage 2: Percentage of Participants With Clinically Meaningful Improvement in EORTC QLQ-C30 Fatigue Scale(Up to approximately 34 months)
- Stage 2: Percentage of Participants With Clinically Meaningful Improvement in FACT-Lym LYMS(Up to approximately 34 months)
- Stage 2: Number of Participants With AEs(From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months))
- Stage 2: Number of Participants With PN(From treatment initiation until 90 days after the last dose of study drug or initiation of NALT (approximately 10.6 months))
- Stage 1 and Stage 2: Number of Participants With Dose Modification for Polatuzumab Vedotin(Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months)
- Stage 1 and Stage 2: Dose Intensity of Polatuzumab Vedotin(Stage 1: Up to approximately 5.3 months and Stage 2: Up to approximately 7.6 months)
- Stage 1: OS(From randomization to the death (up to approximately 34 months))
- Stage 1 and Stage 2: Percentage of Participants With Anti-drug Antibodies (ADAs) to Polatuzumab Vedotin(Up to approximately 34 months)