A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 737
- 试验地点
- 228
- 主要终点
- Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 1
研究概览
简要总结
The purpose of Part 1 of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL; participants may or may not have already had treatment for their cancer. The purpose of Part 2 of this study evaluates pirtobrutinib monotherapy in treatment-naïve participants with CLL/SLL with 17p deletions. Participation could last up to six years for Part 1. Participation could last up to 2 years for Part 2.
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 per iwCLL 2018 criteria
- •Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- •Adequate organ function
- •Platelets greater than or equal to ≥ 50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis,
- •Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
- •Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis
- •Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)
排除标准
- •Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment
- •Known or suspected central nervous system (CNS) involvement
- •A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease
- •Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
- •Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter
- •Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
- •Active cytomegalovirus (CMV) infection
- •Active uncontrolled systemic bacterial, viral, or fungal infection
- •Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
- •Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments
- •Ongoing inflammatory bowel disease
- •Previous treatment for CLL/SLL - Part 1: Treatment-naïve and previously treated, except prior exposure to BTK inhibitor (covalent or noncovalent).
- •Part 2: participants must be treatment naïve
- •Concurrent use of investigational agent or anticancer therapy except hormonal therapy
- •Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
- •Use of > 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug
- •Vaccination with a live vaccine within 28 days prior to randomization
- •Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment
- •Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib
研究组 & 干预措施
Ibrutinib
Participants will receive ibrutinib orally.
干预措施: Ibrutinib (Drug)
Pirtobrutinib Part 1
Participants will receive pirtobrutinib orally.
干预措施: Pirtobrutinib (Drug)
Pirtobrutinib Part 2
Participants will receive pirtobrutinib orally.
干预措施: Pirtobrutinib (Drug)
Ibrutinib Part 1
Participants will receive ibrutinib orally.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 1
时间窗: Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest] (approximately 3 years and 5 months)
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (CRi), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 2
时间窗: Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest (Approximately 2 years and 3 months)
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
次要结局
- IRC-assessed Progression-Free Survival (PFS)(Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months))
- Investigator assessed Progression-Free Survival (PFS)(Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months))
- Event-Free Survival (EFS)(Randomization to first occurrence of treatment discontinuation due to adverse event/toxicity, treatment-emergent atrial fibrillation or atrial flutter of any grade, progressive disease (PD) or death (approximately 4 years))
- Duration of Response (DOR)(Time from the date of the first documented response of CR, CRi, nPR or PR to the earlier of documentation of definitive PD (per iwCLL 2018 criteria) or death from any cause (approximately 2 years))
- Overall Survival (OS)(Randomization to death from any cause (approximately 6 years))
- Time to Next Treatment (TTNT)(Randomization to initiation of the next systemic anticancer therapy for CLL/SLL or death from any cause, whichever occurs first (approximately 6 years))
- Time to Worsening (TTW) of CLL/SLL Related Symptoms(Randomization to time to worsening symptoms (approximately 4 years))
- Comparative Tolerability(From Baseline to Treatment Discontinuation for Any Reason (approximately 4 years))
- Percentage of Participants Achieving DOR Part 2(Time from the date of the first documented response of CR, CRi, nPR, or PR to the earlier of the documentation of definitive PD or death from any cause] (Approximately 2 years))