A Phase II Study of Rituximab/Bendamustine Followed by Rituximab/Cytarabine for Untreated Mantle Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- Complete Remission (CR) Rate After 6 Cycles
研究概览
简要总结
Mantle cell lymphoma (MCL) is not curable with conventional therapy. This study sought to improve upon standard of care in newly diagnosed, untreated MCL patients who were transplant-eligible using drugs already established as active in MCL. The combination of Rituximab-Bendamustine followed by Rituximab-Cytarabine (RB/RC) was expected to maximize pre-ASCT complete response (CR) rate compared to historical rates approximating 55% with tolerable toxicity.
详细描述
This was a PII single-arm design to determine whether the regimen looked promising for further study.
Primary Objective
• To evaluate the efficacy of an alternating regimen of Rituximab-Bendamustine and Rituximab-Cytarabine (RB/RC) using the CR/Cru rate.
Secondary Objectives
- To assess safety.
- To estimate the rate of complete remission (CR), unconfirmed CR (CRu), partial remission (PR), stable disease (SD) and progressive disease (PD).
- To estimate the rate of successful stem cell mobilization after RB/RC in responding patients.
- To estimate the proportion of patients who can successfully complete the regimen and proceed to autologous stem cell transplantation (ASCT).
- To estimate the rate of neutrophil and platelet engraftment after ASCT.
- To estimate the CR/CRu and PR rate for patients with blastoid variant MCL.
- To estimate the rate of minimal residual disease (MRD)-negativity at treatment completion.
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 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mandatory pathologic review of the diagnostic specimen(s) at Brigham and Women's Hospital or Massachusetts General Hospital
- •Measurable disease
- •Candidate for ASCT
排除标准
- •Prior anti-lymphoma therapy
- •Pregnant or breastfeeding
- •Hypersensitivity to rituximab
- •Uncontrolled intercurrent illness
- •Receiving other study agents
- •HIV positive on combination antiretroviral therapy
研究组 & 干预措施
RB/RC
Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to:
- 2 g/m2 for age >60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity;
- 1.5 g/m2 for age >60 years old AND creatinine 114.9-176.8 lmol/l, or for age >60 years old AND pre-existing neurotoxicity;
- 1 g/m2 for age > 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity.
Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study.
干预措施: Rituximab (Drug)
RB/RC
Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to:
- 2 g/m2 for age >60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity;
- 1.5 g/m2 for age >60 years old AND creatinine 114.9-176.8 lmol/l, or for age >60 years old AND pre-existing neurotoxicity;
- 1 g/m2 for age > 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity.
Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study.
干预措施: Bendamustine (Drug)
RB/RC
Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to:
- 2 g/m2 for age >60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity;
- 1.5 g/m2 for age >60 years old AND creatinine 114.9-176.8 lmol/l, or for age >60 years old AND pre-existing neurotoxicity;
- 1 g/m2 for age > 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity.
Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study.
干预措施: Cytarabine (Drug)
结局指标
主要结局
Complete Remission (CR) Rate After 6 Cycles
时间窗: Disease was assessed after three- and six-cycles of therapy, up to approximately 25 weeks. All patients completed 6 cycles of therapy with a cycle duration of 28 days.
The CR rate is defined as the proportion of patients who after 6 cycles of therapy achieve complete remission based on the International Working Group (IWG) Criteria (Cheson et al, 1999), using CT scans. CR or CRu (CR unconfirmed) by CT scans was defined by standard IWG criteria, ie resolution of all abnormal adenopathy and organomegaly, and clearance of marrow disease when present at baseline.
次要结局
- Autologous Stem Cell Transplant (ASCT) Rate(All patients were followed for continuation to ASCT upon completion of induction therapy. Patients usually proceed to ASCT within 3 months of completing induction.)
- 1 Year Progression-Free Survival(Disease was assessed after three- and six-cycles of therapy and in long-term follow-up per standard practice every 6 months until the earliest of relapse, death or 5 years. Median follow-up in this study cohort was 13 months.)
研究者
Christine Ryan
Principal Investigator
Dana-Farber Cancer Institute