Adjustment of Chemotherapy Duration in Follicular Lymphoma Patients According to Peripheral Blood or Bone Marrow Minimal Residual Disease Status
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Progression free survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
研究概览
简要总结
Follicular lymphoma (FL) is a chronic indolent malignancy, where treatment with 6 cycles of bendamustine obinutuzumab (BO) is highly effective but at a cost of increased adverse events.
Tumor specific DNA can be traced in blood and bone marrow of follicular lymphoma patients even after therapy, and when detected after lymphoma treatment it is referred to as minimal residual disease (MRD).
MRD elimination after effective lymphoma treatment is a marker for deep response and correlates with prolonged remission.
In this study we aim to omit chemotherapy after 4 cycles of treatment in patients achieving MRD elimination after 3 months of therapy, as well as complete metabolic response on positron emission computed tomography (PET-CT), hoping to preserve treatment effectiveness while reducing adverse events.
详细描述
Follicular lymphoma (FL) is the second most common type of non-Hodgkin's lymphoma, with an estimated incidence of 3.18 cases per 100000 people a year in the United States The disease is characterized by an indolent behavior, where often treatment is unnecessary at diagnosis, and a "watch & wait" approach is the standard of care for asymptomatic patients. FL is also a highly responsive disease for immuno-chemotherapeutic combinations, although most patients will eventually relapse. Since the disease is incurable & indolent in nature, the therapeutic strategy should aim for disease control, while using treatments with high safety profile in order to minimize the chance for life threatening adverse events.
Therapy with rituximab cyclophosphamide, doxorubicin, vincristine & prednisone (R-CHOP) combination & subsequent rituximab maintenance therapy for 24 months shows excellent results with a median progression free survival (PFS) of above a decade.
The more recent GALLIUM trial has shown that combining the monoclonal antibody obinutuzumab with chemotherapy is even more efficacious compared to rituximab combinations. When different combinations were examined in this trial the best results were achieved with the bendamustine-obinutuzumab (BO) combination with 3 year PFS of 84%. Unfortunately the trial also revealed a downside for this effective combination with higher rate of fatal adverse events among patients receiving 6 cycles of bendamustine combinations.
In patients with acute leukemia evaluation for minimal residual disease (MRD) is a routine procedure, and the nature & length of treatment are guided by MRD status at different time points during therapy.
Among FL patients treated with obinutuzumab-chemotherapy combinations, it has been shown that after 3 cycles of treatment about 90% of patients were MRD negative. In addition MRD negativity at the end of induction in either peripheral blood or bone marrow was found to be associated with improved outcomes in patients with 1st line treatment for FL as well as in the relapsed setting.
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
- •Age 18 and above.
- •FL grade I-IIIa, according to world health organization (WHO) classification, in patients who were not previously treated with chemotherapy, have a high tumor bulk & an indication for treatment, as defined by the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status grade 0-
- •The presence of a molecular marker in bone marrow or peripheral blood for MRD assessment.
排除标准
- •FL grade IIIb.
- •HIV infection.
- •HBsAg positivity.
- •Active malignancy other than FL
- •Pregnancy or lactation.
研究组 & 干预措施
Reduced number of bendamustine cycles in patients with mid-induction MRD negativity
Patients with follicular lymphoma treated with obinutuzumab bendamustine & achieving MRD negativity as well as complete metabolic response on PET-CT at mid-induction would continue obinutuzumab treatment while omitting bendamustin after 4 cycles.
干预措施: Bendamustin (Drug)
Reduced number of bendamustine cycles in patients with mid-induction MRD negativity
Patients with follicular lymphoma treated with obinutuzumab bendamustine & achieving MRD negativity as well as complete metabolic response on PET-CT at mid-induction would continue obinutuzumab treatment while omitting bendamustin after 4 cycles.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Progression free survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
时间窗: Progression free survival will be assessed 24 months after the end of induction.
Progression-free survival is defined as the time from randomization to the earliest event of progression, relapse, or death from any cause. progression-free survival, is assessed by the investigator.
次要结局
- Progression of disease within 24 months (POD24)(POD24 will be assessed at 24 months after treatment initiation)
- Overall survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.(Overall survival will be assessed 24 months after the end of induction.)
- The rate of MRD negativity persistence at 12 months among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.(Persistence of MRD negativity will be assessed 12 months after study initiation.)
- The proportion of adverse events among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.(The proportion of various adverse events will be assessed until 24 months from the end of induction.)