Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 447
- 试验地点
- 1
- 主要终点
- Progression-free Survival as Assessed by Independent Reviewers
研究概览
简要总结
This study is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for ASCT.
详细描述
As rituximab-based regimens have become standard first-line treatment in CD20 positive DLBCL, the efficacy of rituximab combined with salvage chemotherapy in the second-line setting has decreased and there is a need for new therapies in patients progressing or relapsing after first-line rituximab-based therapy. Replacement of rituximab with ofatumumab in the second-line setting, following progression/relapse after first-line rituximab-containing regimens, offers the potential to overcome relative or complete rituximab resistance and thus improve response rates, the ability to proceed to consolidative HDT/ASCT, and overall survival.
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
- •Subjects with CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original diagnosis.
- •Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
- •CT with involvement of 2 or more clearly demarcated lesions/ nodes with a long axis > 1.5 cm and short axis >= 1.0cm or 1 clearly demarcated lesion/ node with a long axis > 2.0 cm and short axis >= 1.0 cm.
- •Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
- •Age 18 yrs or older.
- •ECOG performance status of 0, 1 or
- •Eligible for high dose chemotherapy and 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 first-line rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to or combined with first-line chemotherapy, as maintenance therapy, and radiotherapy in a limited field or as a part of the first-line treatment plan.
- •Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
- •Planned post-randomization chronic glucocorticoid use (limited acute use is allowed and defined by the protocol) unless administered as therapy for mild COPD or asthma.
- •Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years. History of significant cerebrovascular disease.
- •Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.
- •Abnormal/ inadequate WBC count, liver, and kidney function.
- •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 CHEMOTHERAPY REGIMEN
This study is a parallel arm study, with ofatumumab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with ofatumumab. All subjects will receive the same ofatumumab regimen and dose.
干预措施: OFATUMUMAB + DHAP (Drug)
RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN
This study is a parallel arm study, with rituximab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with rituximab. All subjects will receive the same rituximab regimen and dose.
干预措施: RITUXIMAB + DHAP (Drug)
结局指标
主要结局
Progression-free Survival as Assessed by Independent Reviewers
时间窗: From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years)
Progression-free survival is defined as the interval of time from the randomization date until the date of stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for progressive disease \[PD\]) after two cycles of salvage chemotherapy, progression, or death, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data via the Revised Response Criteria for Malignant Lymphoma (RRCML).
次要结局
- Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant(At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months))
- Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy(From the start of each cycle for a maximum of 5 weeks per cycle (assessed during treatment period of Baseline up to approximately 3 months))
- Time to Engraftment After High-dose Therapy (HDT)/ASCT(From ASCT up to 42 days post-ASCT (Baseline up to approximately 4.5 months))
- Number of Participants Completing Autologous Stem Cell Transplant (ASCT)(Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months))
- Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood(During Cycles 2 and/or 3 (Weeks 4-9))
- Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy(At completion of up to 3 cycles of salvage chemoimmunotherapy (assessed up to 9 weeks))
- Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment(Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months]))
- Event-free Survival(From randomization to progressive disease, stable disease after completion of 2 cycles of therapy, commencement of a new treatment for DLBCL, or death due to any cause (assessed for up to 5 years))
- Overall Survival (OS)(From randomization to death due to any cause (assessed for up to 5 years))
- Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment(Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months]))