NCT03123393终止2 期
Phase 2 Study of TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After at Least 2 Prior Lines of Chemotherapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 49
- 试验地点
- 41
- 主要终点
- Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria
研究概览
简要总结
The purpose of this study is to assess the efficacy of TAK-659 measured by independent radiologic review committee (IRC)-assessed overall response rate (ORR) in participants with relapsed or refractory DLBCL.
详细描述
The drug being tested is TAK-659. This study will evaluate overall response rate (ORR) in participants with relapsed or refractory DLBCL who take TAK-659.
The study will enroll approximately 122 participants. Participants will be assigned to:
• TAK-659 60 mg to 100 mg
All participants will be asked to take the tablets of TAK-659 at the same time each day throughout the study in a 28-day cycle.
This multi-center trial will be conducted in the United States, United Kingdom, Spain, Italy, France, Canada, Germany. The overall time to participate in this study is approximately 48 months. Participants will be assessed for disease response and progression during the PFS follow-up every 3 months after end of treatment (for participants who discontinue due to reasons other than disease progression) and OS follow-up every 3 months from the last dose of study drug until death or conclusion of the study, whichever occurs first.
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
- •Must have histologically confirmed DLBCL, including de novo disease or transformed disease from indolent NHL.
- •a. High-grade B-cell lymphoma (BCL) with MYC and BCL-2 and/or BCL-6 translocations (double-hit DLBCL under DLBCL, not otherwise specified [NOS], based on the 2008 World Health Organization [WHO] classification criteria) is not eligible for this study.
- •Local pathology review for histological confirmation; A formalin-fixed, paraffin-embedded (FFPE) tumor block or appropriately stained slides from a fresh biopsy is required.
- •Relapsed or refractory to greater than or equal to (>=) 2 prior lines of chemotherapy based on standard of care with certain requirements for prior therapy.
- •Documented investigator-assessed relapse or progression after the last treatment is required if the participant responded and then progressed on the prior treatment.
- •Measurable disease per IWG 2007 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status less than (<)
- •Life expectancy of greater than (>) 3 months.
- •Adequate organ function, including the following:
- •Bone marrow reserve: absolute neutrophil count (ANC) >=1000/microliter (μL), platelet count >=75,000/μL (>=50,000/μL for participants with bone marrow involvement), and hemoglobin >=8 gram per deciliter (g/dL).
- •Hepatic: total bilirubin less than or equal to (<=) 1.5 times the upper limit of the normal range (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5*ULN.
- •Renal: creatinine clearance >=60 milliliter per minute (mL/min).
- •Lipase <=1.5*ULN and amylase <=1.5*ULN with no clinical symptoms suggestive of pancreatitis or cholecystitis.
- •Blood pressure <=Grade 1 (hypertensive participants are permitted if their blood pressure is controlled to <=Grade 1 by hypertensive medications.
- •Glycosylated hemoglobin is <=6.5% hyperglycemic participants permitted if glucose is well controlled by antihyperglycemic medication).
排除标准
- •Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases.
- •Known human immunodeficiency virus (HIV)-related malignancy.
- •Systemic anticancer treatment (including investigational agents) less than 3 weeks before the first dose of study treatment (<=4 weeks for antibody-based therapy including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell engager agents; <=8 weeks for cell-based therapy or anti-tumor vaccine).
- •Radiotherapy less than 3 weeks before the first dose of study treatment. If prior radiotherapy occurred <4 to 6 weeks before study start, as radiated lesions cannot be reliably assessed by fluorodeoxyglucose-positron emission tomography (FDG-PET), nonradiated target lesions are required for eligibility, and prior radiotherapy information must be submitted to the IRC.
- •Known HIV positive, hepatitis B surface antigen positive or known or suspected active hepatitis C infection.
- •Prior autologous stem cell transplant (ASCT) within 6 months or prior ASCT at any time without full hematopoietic recovery before Cycle 1 Day 1, or allogeneic stem cell transplant any time.
- •Participants with certain cardiovascular conditions are excluded.
- •Major surgery within 14 days before the first dose of study drug or incomplete recovery from any complications from surgery.
- •Systemic infection requiring parenteral antibiotic therapy or other serious infection (bacterial, fungal, or viral) within 21 days before the first dose of study drug.
- •Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of TAK-
- •Participants with another malignancy within 2 years of study start. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry.
- •Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-
- •Received medications, supplements, or food/beverages that are P-glycoprotein (P-gp) inhibitors or inducers or strong cytochrome P450 (CYP) 3A inhibitors or inducers within a certain timeframe prior to the first dose of study drug. Depending on the substance, the washout period for P-gp inhibitors or inducers or strong CYP3A inhibitors or inducers will be either 7 days or 5 times the half-life (half-life is related to the time required for elimination from the body). The washout period for grapefruit containing food or beverages is 5 days.
研究组 & 干预措施
Cohort A: TAK-659 100 mg
Experimental
TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).
干预措施: TAK-659 (Drug)
Cohort B: TAK-659 Ramp-up Dosing
Experimental
TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).
干预措施: TAK-659 (Drug)
结局指标
主要结局
Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria
时间窗: Up to 12 months
ORR was defined as the percentage of participants with complete response (CR), or partial response (PR) as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
次要结局
- Stage 2: CR Rate as Assessed by IRRC Based on 2014 IWG-Lugano Criteria(Up to 12 months)
- Stage 2: CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria(Up to 12 months)
- Stage 2: Duration of Response (DOR)(Up to 12 months)
- Stage 2: ORR as Assessed by IRRC Based on 2014 IWG-Lugano Criteria(Up to 12 months)
- Stage 2: ORR as Assessed by IRC in Participants With DLBCL Transformed From Indolent Non-Hodgkin's Lymphoma (NHL)(Up to 12 months)
- Stage 1: ORR as Assessed by IRRC to Select Stage 2 Dose Regimen of TAK-659 From the Lead-in Dose Exploration Phase(Up to 12 months)
- Stage 2: Duration of CR(Up to 12 months)
- Stage 2: ORR as Assessed by IRRC in Participants With Germinal Center B-cell (GCB) DLBCL(Up to 12 months)
- Stage 2: ORR as Assessed by IRC at 3, 6, and 9 Cycles in Participants With DLBCL(At Cycles 3, 6 and 9 (Up to 12 months) (Each cycle of 28 days))
- Stage 2: Progression Free Survival (PFS) as Assessed by IRC(Up to 18 months)
- Stage 2: Overall Survival (OS)(Up to 24 months)
研究者
研究点 (41)
Loading locations...
相似试验
进行中（未招募）
1 期
TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell LymphomaRelapsed or Refractory Diffuse Large B-Cell LymphomaMedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851EUCTR2016-003716-12-ESMillennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited82
进行中（未招募）
1 期
TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell LymphomaRelapsed or Refractory Diffuse Large B-Cell LymphomaMedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851EUCTR2016-003716-12-DEMillennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited122
进行中（未招募）
1 期
TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell LymphomaRelapsed or Refractory Diffuse Large B-Cell LymphomaMedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851EUCTR2016-003716-12-GBMillennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited122
进行中（未招募）
1 期
TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell LymphomaRelapsed or Refractory Diffuse Large B-Cell LymphomaMedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851EUCTR2016-003716-12-ITMILLENNIUM PHARMACEUTICALS, INC.49
终止
1 期
Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition Ofthe Proteasome Inhibitor IxazomibAML, AdultAMLNCT04079738H Scott Boswell8