A Phase II Study of Ofatumumab-Based Induction Chemoimmunotheraphy Followed by Consolidation Ofatumumab Immunotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Progression Free Survival Rate 2 Years After Initiation of Induction Therapy
研究概览
简要总结
Background:
- Ofatumumab was approved by the U.S. Food and Drug Administration to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not responded to standard chemotherapy. Ofatumumab is a substance that recognizes specific types of white blood cells called B-lymphocytes, which become cancerous in CLL/SLL. Ofatumumab attaches to a molecule called CD20, which is found on the surface of B-cells, and destroys them. Previous studies have shown that ofatumumab can decrease the number of B-cells in patients with CLL/SLL who have been treated with chemotherapy, but more research is needed to determine it if can also be used to treat patients with previously untreated CLL/SLL.
Objectives:
- To determine a safe and effective dose of ofatumumab, along with chemotherapy, to treat chronic lymphocytic leukemia or small lymphocytic lymphoma.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with CLL or SLL that has not been treated with chemotherapy.
Design:
- Eligible participants will be screened with a physical exam, blood samples, lymph node and bone marrow biopsies, and imaging studies.
- Participants will be separated into 2 groups: all participants will receive ofatumumab and fludarabine, and some participants will be selected to also receive cyclophosphamide (based on results of certain blood tests).
- Participants will receive the study drugs (ofatumumab and fludarabine, and optional cyclophosphamide) by infusion for a maximum of 6 days, followed by 21 days off drug.
- Participants will have 6 cycles of treatment according to a schedule set by the study doctors, and may have their dose levels adjusted if side effects develop.
- Participants who have disease remaining after 6 cycles will receive additional ofatumumab every 2 months, starting 2 months after the end of the 6th cycle and continuing for a total of 4 doses, before entering the follow-up phase of the trial. Participants who do not have residual disease after 6 cycles will not receive additional therapy, and will immediately enter the follow-up phase of the trial.
- Participants will have a follow-up exam every 2 to 4 months for 2 years after the end of treatment, and then as required by the study doctors for as long as the study remains open. These visits will involve a full medical exam, blood samples, lymph node and bone marrow biopsies, and imaging studies.
详细描述
OUTLINE:
Patients with adverse interphase cytogenetics (11q22 or 17p13 deletion) receive FCO induction therapy:
- Ofatumumab is given IV on day 1 (300 mg) and day 8 (1000 mg) of course 1 and on day 1 (1000 mg) of all subsequent courses.
- Fludarabine phosphate (25mg/m2/d) and cyclophosphamide (250mg/m2/d) are given IV on days 2 through 4 of course 1 and on days 1 through 3 of all subsequent courses. Patients age 70 or older will be given reduced doses of fludarabine (20mg/m2/d) and cyclophosphamide (150mg/m2/d).
- Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.
Patients without adverse interphase cytogenetics receive FO induction therapy:
- Ofatumumab is given IV on day 1 (300mg) and day 8 (1000mg) of course 1 and on day 1 (1000mg) of all subsequent courses.
- Fludarabine phosphate (25mg/m2/d) is given IV on days 2 through 6 of course 1 and on days 1 through 5 of all subsequent courses.
- Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
FO Arm (fludarabine and ofatumumab)
For patients with non-high risk FISH changes
干预措施: Fludarabine Phosphate (Drug)
FO Arm (fludarabine and ofatumumab)
For patients with non-high risk FISH changes
干预措施: Ofatumumab (Biological)
FCO Arm (fludarabine, cyclophosphamide, and ofatumumab)
For patients with high risk FISH changes
干预措施: Fludarabine Phosphate (Drug)
FCO Arm (fludarabine, cyclophosphamide, and ofatumumab)
For patients with high risk FISH changes
干预措施: Ofatumumab (Biological)
FCO Arm (fludarabine, cyclophosphamide, and ofatumumab)
For patients with high risk FISH changes
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Progression Free Survival Rate 2 Years After Initiation of Induction Therapy
时间窗: 2 years
Death or disease progression defined by the 2008 IWCLL guideline as follows; * Greater than or equal to 50% increase in the SPD of at least 2 lymph nodes (at least one node must be greater than or equal to 2 cm); appearance of any new lymph nodes on physical examination or imaging * Greater than or equal to 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin or CT scan or appearance of palpable hepatomegaly or splenomegaly, which was not previously present * Greater than or equal to 50% increase in the absolute number of circulating lymphocytes to at least 5000/ul * Transformation to a more aggressive histology * Occurrence of any cytopenia attributable to CLL. After treatment: the progression of any cytopenia (unrelated to autoimmune cytopenia), as documented by a decrease of Hb levels by more than 20 g/L (2 g/dL) or to less than 100 g/L (10 g/dL), or by a decrease of platelet counts by more than 50% or to les
次要结局
- Number of Grade 3 and 4 Treatment Related Adverse Events(2 years)
- Participants With Complete Response Rates Following Induction Chemoimmunotherapy.(2 years)
- Participants Overall Response Rates Following Induction Chemoimmunotherapy.(2 years)
- Participants With Minimal Residual Disease (MRD) Negativity(2 years)
- Participants Overall Survival Rate After Initiation of Induction Chemoimmunotherapy(Up to 2 years)
- Median Relationship of CD20 Expression With MRD Negativity Rate(2 years)
- Participants With MRD Negativity at the Completion of Consolidation Immunotherapy Who Failed to Achieve MRD Negativity(2 years)