A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 238
- 试验地点
- 439
- 主要终点
- Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)
研究概览
简要总结
This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four years, and possibly longer, if the disease does not progress.
详细描述
This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (Arm A) to investigator's choice of either idelalisib plus rituximab or bendamustine plus rituximab (Arm B) in CLL/SLL patients who have been treated with at least a covalent BTK inhibitor (BTKi). Patients may have discontinued the prior covalent BTKi due to disease progression (PD) or intolerance. Patients who have received venetoclax are eligible for the study. Eligible patients will be randomized in 1:1 to Arm A or Arm B.
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
- •Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria.
- •Previously treated with a covalent BTK inhibitor.
- •Eastern Cooperative Oncology Group (ECOG) 0-
- •Absolute neutrophil count ≥ 0.75 × 10^9/L without granulocyte-colony-stimulating factor support, or ≥ 0.50 × 10^9/L in patients with documented bone marrow involvement considered to impair hematopoiesis. Granulocyte-colony-stimulating factor support is permitted in patients with documented bone marrow involvement.
- •Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Transfusion support is permitted in patients with bone marrow involvement.
- •Platelets ≥ 50 × 10^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75 × 10^9/L. Patients may enroll below these thresholds if the Investigator determines the cytopenia is related to bone marrow involvement considered to impair hematopoiesis. Patients with a platelet count < 30 x 10^9/L are excluded.
- •AST and ALT ≤ 3.0 x upper limit of normal (ULN).
- •Total bilirubin ≤ 1.5 x ULN.
- •Estimated creatinine clearance of ≥ 30 mL/min.
排除标准
- •Known or suspected Richter's transformation at any time preceding enrollment.
- •Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.
- •Ongoing drug-induced liver injury.
- •Active uncontrolled auto-immune cytopenia.
- •Significant cardiovascular disease.
- •History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor-modified T cells (CAR-T) therapy within the past 60 days.
- •Active hepatitis B or hepatitis C.
- •Known active cytomegalovirus (CMV) infection.
- •Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
- •Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.
- •Clinically significant active malabsorption syndrome or inflammatory bowel disease
- •Prior exposure to non-covalent (reversible) BTK inhibitor.
- •Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
- •Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers.
- •Vaccination with a live vaccine within 28 days prior to randomization.
- •Patients with the following hypersensitivity:
- •Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-
- •For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine.
- •Prior significant hypersensitivity to rituximab.
研究组 & 干预措施
Arm A - Pirtobrutinib
Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
干预措施: Pirtobrutinib (Drug)
Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab
Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m^2 every 4 weeks (Q4W) or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.
干预措施: Idelalisib (Drug)
Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab
Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m^2 every 4 weeks (Q4W) or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.
干预措施: Bendamustine (Drug)
Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab
Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m^2 every 4 weeks (Q4W) or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.
干预措施: Rituximab (Drug)
结局指标
主要结局
Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)
时间窗: Randomization to Disease Progression or Death Due to Any Cause (Up to 29 Months)
PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an IRC according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018.
次要结局
- PFS Assessed by Investigator(Randomization to Disease Progression or Death Due to Any Cause (Up to 36 Months))
- Overall Survival (OS)(Randomization to Death from Any Cause (Up to 36 months))
- Time to Next Treatment (TTNT)(Randomization to Subsequent Anticancer Therapy, Therapy of Pirtobrutinib or Death Due to Any Cause (Up to 36 Months))
- Event Free Survival (EFS)(Randomization to Disease Progression, Subsequent Anticancer Therapy, Unacceptable Toxicity Leading to Treatment Discontinuation, or Death Due to Any Cause (Up to 36 Months))
- Percentage of Participants With Overall Response Rate (ORR) Assessed by Investigator(Randomization to Subsequent Anticancer Therapy, Disease Progression or Death Due to Any Cause (Up to 36 Months))
- Time to Worsening (TTW) of CLL/SLL Related Symptoms(Baseline up to Week 25 (Arm A and Arm B - Idelalisib plus Rituximab) & Baseline up to Week 21 + Safety Follow-Up of up to 5 Weeks (Arm B - Bendamustine plus Rituximab))
- Time to Worsening (TTW) of Physical Function(Baseline up to Week 25 (Arm A and Arm B - Idelalisib plus Rituximab) & Baseline up to Week 21 + Safety Follow-Up of up to 5 Weeks (Arm B - Bendamustine plus Rituximab))