A Single Arm, Safety and Efficacy Study of Ofatumumab in Combination With ICE or DHAP Chemotherapy in Relapsed or Refractory Aggressive Lymphoma Prior to Autologous Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 61
- 主要终点
- Number of Participants With Overall Response (OR), as Assessed by the Investigator
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of ofatumumab used in combination with ifosfamide, carboplatin, etoposide (ICE) or dexamethasone, cytarabine, cisplatin (DHAP) salvage chemotherapy regimens in subjects with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are eligible for autologous stem cell transplant.
详细描述
Rituximab combined with anthracycline based chemotherapy is the most common first-line treatment for subjects with diffuse large B cell lymphoma (DLBCL). Subjects requiring second-line therapy will most often receive rituximab in combination with salvage chemotherapy as an induction therapy prior to autologous stem cell transplant. With rituximab being in first-line therapy, the response rates for subjects receiving rituximab plus salvage chemotherapy has significantly decreased. Treatment with ofatumumab may be able to overcome the resistance to rituximab in the second-line setting and offer improved response rates. The objective of this study is to evaluate the overall response rate of ofatumumab in combination with ICE or DHAP chemotherapy prior to autologous stem cell transplant. Additional objectives are to evaluate the complete response rate, ability to mobilize cluster of differentiation (CD)34+ cells, progression-free survival (PFS) and overall survival.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with CD20 positive aggressive non-Hodgkin's lymphoma (NHL) including DLBCL, transformed follicular lymphoma (FL) & grade 3b FL.
- •Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
- •Computed tomography (CT) with involvement of 2 or more clearly demarcated lesions with a long axis > 1.5 centimeters (cm) and short axis ≥ 1.0 cm or 1 clearly demarcated lesion with a long axis >2.0 cm and short axis ≥1.0 cm.
- •Baseline [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
- •Age 18 yrs or older.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
- •Eligible for high dose chemotherapy and autologous stem cell transplant (ASCT).
- •Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation.
- •Signed written informed consent.
排除标准
- •Previous cancer therapy for lymphoma, with the exception of required rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to first-line therapy and / or as a maintenance therapy, or limited field radiotherapy (as defined by the protocol).
- •Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
- •Chronic Glucocorticoid use (limited acute use is allowed and defined by the protocol).
- •History of significant cerebrovascular disease.
- •Abnormal/ inadequate white blood cell (WBC) count, liver, and kidney function.
- •Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years.
- •Known or suspected hypersensitivity to study treatments.
- •Prior treatment with anti-CD20 monoclonal antibodies, at any time, or treated with other monoclonal antibodies within 3 months prior to start of study therapy, with the exception of rituximab in both instances.
- •Inability to comply with the protocol activities.
- •Pregnant or lactating women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception during and up to 1 year following dosing completion.
研究组 & 干预措施
ofatumumab + DHAP or ICE chemotherapy regimen
This study is a single arm study, but the Investigators are required to prospectively choose to treat all of their subjects with either ICE or DHAP chemotherapy regimens in combination with ofatumumab. Regardless of whether the subject receives ICE or DHAP chemotherapy, all subjects will receive the same ofatumumab regimen and dose.
干预措施: ofatumumab + ICE (Drug)
ofatumumab + DHAP or ICE chemotherapy regimen
This study is a single arm study, but the Investigators are required to prospectively choose to treat all of their subjects with either ICE or DHAP chemotherapy regimens in combination with ofatumumab. Regardless of whether the subject receives ICE or DHAP chemotherapy, all subjects will receive the same ofatumumab regimen and dose.
干预措施: ofatumumab + DHAP (Drug)
结局指标
主要结局
Number of Participants With Overall Response (OR), as Assessed by the Investigator
时间窗: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3
Responders with OR included participants with complete response (CR) and partial response (PR). This was based on adequate responses from the investigator assessment after the completion of treatment. CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR: at least a 50% decrease from baseline in the sum of the product of the diameters of target lesions.
次要结局
- Number of Participants With CR, as Assessed by the Investigator(From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3)
- Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram (kg) From Peripheral Blood(During treatment Cycle 2 (Study Days 22-42) and/or Cycle 3 (Study Days 43-63))
- Progression-free Survival (PFS)(From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3)
- Clearance (CL) of Ofatumumab(Study Day 1 up to Study Day 85 (up to 12 weeks))
- Overall Survival(From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3)
- Area Under the Concentration-time Curve From Time Zero to Infinity, AUC(0-inf), of Ofatumumab at the First Infusion (Cycle 1, Day 1) and the Last Infusion (Cycle 3)(Cycle 1 Day 1 (Study Day 1; up to 1 week) and Cycle 3 (Study Day 43; up to 6 weeks))
- Area Under the Concentration-time Curve During the Dosing Interval (AUC(0-tau)) of Ofatumumab at the Last Infusion (Cycle 3)(Cycle 3 (Study Day 43; 3 weeks))
- Maximum Plasma Concentration (Cmax) of Ofatumumab at the First Infusion (Cycle 1 Day 1), Second Infusion (Cycle 1 Day 8), and Last Infusion (Cycle 3)(Cycle 1 Day 1 (Study Day 1; up to 48 hours), Cycle 1 Day 8 (Study Day 8; up to 24 hours), Cycle 3 (Study Day 43; up to 48 hours))
- Trough Plasma Concentration (Ctrough) of Ofatumumab Prior to Second Infusion (Cycle 1 Day 8), Third Infusion (Cycle 2), and Last Infusion (Cycle 3)(Cycle 1 Day 8 (Study Day 8; up to 8 hours prior to infusion start), Cycle 2 (Study Day 22; up to 7 hours prior to infusion start), Cycle 3 (Study Day 43; up to 6 hours prior to infusion start))
- Terminal Phase Half-life (t1/2) of Ofatumumab(Study Day 1 up to Study Day 85 (up to 12 weeks))
- Volume of Distribution at Steady State (Vss) of Ofatumumab(Study Day 1 up to Study Day 85 (up to 12 weeks))
- Number of Participants With the Indicated AEs Associated With Decreased Hemoglobin Counts(Study Day 1 to approximately Study Day 63)
- Number of Participants Who Were Positive and Negative for Human Anti-human Antibodies (HAHA) at the Indicated Time Points(Study Day 1 up to approximately Study Day 63)
- Number of Participants With the Indicated Adverse Events (AEs) Associated With Neutropenia(Study Day 1 to approximately Study Day 63)
- Number of Participants With the Indicated AEs Associated With Decreased Platelet Counts(Study Day 1 to approximately Study Day 63)