A Phase 2/3 Multi-center Study to Evaluate the Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Phase 2: Percentage of Participants Who Achieved Complete Metabolic Response (CMR)
研究概览
简要总结
This is a phase 2/3 open label, multicenter trial testing blinatumomab monotherapy for the treatment of subjects with Relapsed/Refractory (R/R) aggressive B-NHL not achieving CMR after 2 cycles of standard platinum-based chemotherapy regimens administered as S1. This study incorporates multiple interim analyses for futility, efficacy, and unblinded sample-size re-estimation. In the phase 3 part of the study, blinatumomab will be compared to Investigator's Choice chemotherapy.
In March 2019, decision made to not proceed with phase 3.
详细描述
This is a phase 2/3 open label, multicenter trial testing blinatumomab monotherapy for the treatment of subjects with R/R aggressive B-NHL not achieving CMR after standard platinum-based chemotherapy regimens administered as S1. This study incorporates multiple interim analyses for futility, efficacy, and unblinded sample-size re-estimation. In the phase 3 part of the study, blinatumomab will be compared to IC chemotherapy.The phase 2 component of the study will consist of up to a 28-day screening period, approximately 70 to 112 days of study treatment, a 30-day (+/- 3days) safety follow up, and long-term follow up that will conclude with the final analysis of the phase 3 component, estimated at 30 months after initiation of the phase 3 component. For the phase 3 component, the study will consist of up to a 28-day screening period, a treatment period of up to approximately 168 days, a 30-day safety follow-up visit, and long-term follow up. Long-term follow up will conclude with the final analysis.In the phase 2 component, enrolled subjects will receive blinatumomab monotherapy. In the phase 3 component, enrolled subjects will be randomized in a 1:1 ratio to blinatumomab or IC chemotherapy.
In March 2019, decision made to not proceed with phase 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Biopsy proven aggressive B-cell Non-Hodgkin Lymphoma (B-NHL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), follicular lymphoma Grade 3B, PMBCL, T-cell rich B-cell lymphoma, or DLBCL that represents transformation of indolent non-Hodgkin's Lymphoma (NHL), (including follicular, marginal zone, and lymphoplasmacytoid lymphoma) excluding chronic lymphocytic leukemia or Hodgkin Lymphoma. The following histologies are not eligible:
- •Lymphoblastic lymphoma
- •Burkitt lymphoma
- •Mantle cell lymphoma Any histologies not specifically mentioned must be discussed with medical monitor.
- •Refractory (no prior CR/CMR) or relapsed (prior CMR) following front line treatment of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. For subjects with refractory disease and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy
- •Biopsy proven confirmation of relapsed disease.
- •Received a minimum of 2 cycles of standard of care platinum-based chemotherapy in the S1 setting and had a response of progressive metabolic disease (PMD), no metabolic response (NMR), partial metabolic response (PMR) as centrally assessed by PET-/ CT scan or received at least 1 cycle of S1 chemotherapy and had evidence of PMD as centrally assessed. A pre-salvage scan is required to be submitted to the central reader if a subject had only 1 cycle of pre-salvage chemotherapy.
- •Radiographically measurable disease with a demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension
- •Eastern Cooperative Oncology Group performance status less than or equal to 2
- •Intention to proceed to high dose chemotherapy (HDT) and autologous hematopoietic stem cell transplant (HSCT)
- •Laboratory parameters:
- •Hematology:
- •Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
- •Platelets ≥ 75 x 10^9/L
- •Creatinine clearance ≥ 50 mL/min
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)
- •Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)
排除标准
- •CMR following S1 chemotherapy
- •Treatment within 30 days prior to randomization with another investigational device or drug study (ies).
- •Prior anti-CD19-directed therapies
- •Prior HDT with autologous HSCT
- •Prior allogeneic HSCT
- •Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
- •Evidence of CNS involvement by NHL
- •Known infection with human immunodeficiency virus or chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (anti hepatitis C virus positive)
- •History of malignancy other than B-NHL within the past 3 years with the exception of:
- •Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment
- •Adequately treated non-melanoma skin cancer or lentigo maligna
- •Adequately treated cervical carcinoma in situ
- •Adequately treated breast ductal carcinoma in situ
- •Prostatic intraepithelial neoplasia without evidence of prostate cancer
- •Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
- •Known sensitivity to immunoglobulins or any of the components to be administered during dosing.
- •Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required procedures.
- •History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- •Female subjects who are pregnant or breastfeeding or planning to become pregnant or breastfeed, or of childbearing potential unwilling to use an effective method of contraception while receiving, and for an additional 48 hours after the last dose of blinatumomab.
研究组 & 干预措施
Blinatumomab
Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab is continuous infusion with step dosing of 9 µg/day x 7 days, 28 µg/day x 7 days, and 112 µg/days until the end of the cycle.
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Phase 2: Percentage of Participants Who Achieved Complete Metabolic Response (CMR)
时间窗: Up to 12 weeks after first dose of blinatumomab
Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.
Phase 3: Number of Participants Who Achieved Complete Metabolic Response (CMR)
时间窗: Up to 12 weeks after first dose of study treatment
Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.
次要结局
- Phase 3: Objective Response Rate (ORR)(Up to 12 weeks after first dose of study treatment)
- Phase 3: Duration of Response (DOR)(From first dose of study treatment up to 12 weeks)
- Phase 2: Cumulative Incidence Function Estimate of 100-day Mortality After HSCT Presented as Percentage of Participants That Died Not Due to Relapse, With Relapse and Death Due to Relapse as Competing Events(100 days after HSCT)
- Phase 2: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)(From first dose of blinatumomab until 30 days after last dose. The maximum treatment duration for blinatumomab was 114 days)
- Phase 2: Progression Free Survival (PFS)(From first dose of blinatumomab until the end of study, up to 30 months)
- Phase 2: Blinatumomab Steady State Concentrations (Css)(Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days))
- Phase 2: Blinatumomab Clearance (CL)(Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days))
- Phase 2: Half-life of Blinatumomab(Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days))
- Phase 2: Overall Survival (OS)(From randomization until the end of study, up to 30 months)
- Phase 2: Duration of Response (DOR)(From first dose of blinatumomab up to 12 weeks)
- Phase 2: Percentage of Participants Who Experienced Successful Mobilization(From first dose of blinatumomab until the end of study, up to 30 months)
- Phase 3: Progression Free Survival (PFS)(From first dose of study treatment until the end of study, up to 30 months)
- Phase 3: Percentage of Participants Who Experienced Successful Mobilization(From baseline until the end of study, up to 30 months)
- Phase 3: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT)(From baseline HSCT until the end of study, up to 30 months)
- Phase 3: Change From Baseline in Patient Reported Clinical Outcome Assessments Quality of Life (QOLCOA) Scores(Up to 30 days after last dose after study treatment)
- Phase 3: Blinatumomab Clearance (CL)(Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days))
- Phase 2: Objective Response Rate (ORR)(Up to 12 weeks after first dose of blinatumomab)
- Phase 2: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT)(From baseline HSCT until the end of study, up to 30 months)
- Phase 3: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)(From first dose of study treatment until 30 days after last dose)
- Phase 3: Half-life of Blinatumomab(Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days))
- Phase 3: Percentage of Participants Who Died Within 100 Days After Hematopoietic Stem Cell Transplantation (HSCT) That Was Not Due to Relapse(100 days after HSCT)
- Phase 3: Serum Blinatumomab Steady State Concentration (Css)(24 hours after first dose of blinatumomab)