A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 500
- 试验地点
- 350
- 主要终点
- To compare progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL)
研究概览
简要总结
This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two 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 pirtobrutinib (Arm A) to investigator's choice of ibrutinib, acalabrutinib or zanubrutinib (Arm B) in MCL patients who have received 1 or more lines of therapy and are BTK inhibitor naïve.
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 MCL diagnosis
- •Previously treated with at least one prior line of systemic therapy for MCL
- •Measurable disease per Lugano criteria
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening
- •Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7 days of screening
- •Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening.
- •AST and ALT ≤ 3.0 x upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 x ULN.
- •Creatinine clearance of ≥ 30 mL/min according to Cockcroft/Gault Formula
排除标准
- •Prior treatment with an approved or investigational BTK inhibitor
- •History of bleeding diathesis
- •History of stroke or intracranial hemorrhage within 6 months of randomization
- •History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization
- •Clinically significant cardiovascular disease
- •Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3 consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs
- •Known HIV infection or active HBV, HCV, or CMV infections. (Certain participants with controlled HBV infections may still be eligible)
- •Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption
- •Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.
- •Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
- •Vaccination with live vaccine within 28 days prior to randomization
研究组 & 干预措施
Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib)
Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.
干预措施: Acalabrutinib (Drug)
Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib)
Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.
干预措施: Zanubrutinib (Drug)
Arm A (Pirtobrutinib)
Orally
干预措施: Pirtobrutinib (Drug)
Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib)
Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
To compare progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL)
时间窗: Up to approximately 24 months
Assessed per Lugano criteria
次要结局
- To compare Overall Response Rate (ORR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms(Up to approximately 24 months)
- To compare Overall Survival of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms(Up to approximately 24 months)
- To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms(Up to approximately 24 months)
- To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms(Up to approximately 24 months)
- Time to worsening (TTW) of MCL-related symptoms(Up to approximately 24 months)
- Comparative Tolerability as measured by proportion of time with high side effect burden(Up to approximately 24 months)
- To compare Duration of Response (DOR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms(Up to approximately 24 months)