Phase II Study of Venetoclax (ABT-199/GDC-0199) in Combination With Obinutuzumab and Bendamustine in Patients With High Tumor Burden Follicular Lymphoma as Front Line Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- PrECOG, LLC.
- 入组人数
- 56
- 试验地点
- 10
- 主要终点
- Complete Response (CR) at End of Induction
研究概览
简要总结
Patients with high tumor burden, low grade follicular lymphoma that has never been treated, will receive venetoclax in combination with obinutuzumab and bendamustine.
Venetoclax is an oral Bcl-2 family protein inhibitor. It targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with follicular lymphoma. Venetoclax may help to slow down the growth of cancer or may cause cancer cells to die.
The purpose of this study is to see whether adding venetoclax to obinutuzumab and bendamustine improves the response (the tumor shrinks or disappears) in patients with follicular lymphoma.
As of 9/5/2018, a higher than expected incidence of tumor lysis syndrome (TLS) was experienced among patients receiving venetoclax, obinutuzumab and bendamustine on Cycle 1, Day 1 of treatment. TLS is caused by the fast breakdown of cancer cells. These patients developed an increase in some of their blood tests (uric acid, phosphorus, potassium and/or creatinine). They received a medication called rasburicase and continued with treatment. It is unclear if the TLS was due to the venetoclax or the standard treatment of obinutuzumab and bendamustine. For the remaining patients, venetoclax will start on Cycle 2, Day 1 (previously Cycle 1, Day 1).
As of 9/16/2021, additional maintenance therapy has been suspended for those patients who remain on study. These patients will not receive any further treatment and will move on to the two year survival follow-up.
详细描述
Follicular lymphoma (FL) is the most common low grade lymphoma comprising 70% of low-grade non-Hodgkin's lymphoma (NHL) and 22% of all cases of NHL. The survival rates for patients with indolent NHL remained unchanged from the 1950s through the early 1990s, but recent evidence suggests that outcomes continue to improve. High-risk patients with FL, defined as having advanced stage and high tumor burden have significantly shorter progression free survival despite significant advances.
This is an open-label phase II study of venetoclax in combination with obinutuzumab and bendamustine. Patients will receive induction therapy with obinutuzumab and bendamustine for six cycles (1 cycle = 28 days). Venetoclax will start with 2nd cycle of induction therapy (previously started with cycle 1). There will be a formal, detailed toxicity evaluation after 21 patients complete 3 cycles of treatment.
Patients who achieve partial response or stable disease will receive therapy with obinutuzumab every 2 months for 12 cycles and venetoclax every month for 24 cycles. Patients who achieve a complete response will receive obinutuzumab every 2 months for 12 cycles. Patients with progressive disease will not continue onto the maintenance arm.
Tumor assessments will be performed approximately every 12 weeks during induction and every 6 months during maintenance therapy.
Mandatory pre-treatment tumor tissue sample (i.e., obtained during a previous procedure or biopsy) will be required for research (if sufficient tissue is available). Optional tumor biopsy samples obtained during treatment or post-treatment will also be requested for research.
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 —（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
Induction Venetoclax
Cycle 1-6: Obinutuzumab intravenously (IV) and bendamustine IV. Cycle 2-6: Venetoclax (oral)
干预措施: Induction Venetoclax (Drug)
Maintenance Venetoclax
Patients with stable or improved disease will receive venetoclax by mouth daily for 24 cycles (1 cycle=1 month) and obinutuzumab IV every 2 months for 12 cycles. Patients with no evidence of disease will receive obinutuzumab IV every 2 months for 12 cycles.
干预措施: Maintenance Venetoclax (Drug)
结局指标
主要结局
Complete Response (CR) at End of Induction
时间窗: After 6 cycles (at 28 days/cycle) of induction therapy.
CR assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
次要结局
- Convert to CR During Maintenance Therapy (From PR in Induction)(Up to 24 cycles which corresponds to 22 months (at 28 days/cycle))
- Progression-Free Survival (PFS) in the Intent to Treat (ITT) Population.(Up to 24 months)
- Patient Compliance in Receiving Induction Therapy(Up to 6 cycles (at 28 days/cycle))
- Number of Participants With Treatment-related GRADE 3+ Adverse Events as Assessed by CTCAE V4.0(Adverse events were captured through 6 cycles of therapy (at 28 days/cycle) and for 30 days after the last dose, for a total assessment period of approximately 7 months.)
- Overall Response Rate (ORR)(After 6 cycles (at 28 days/cycle) of induction therapy)
- Overall Survival (OS) in the ITT Population.(Up to 24 months)