An Open Label, Multicenter, Exploratory Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 9
- 主要终点
- Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment
研究概览
简要总结
The purpose of this study is to determine whether the bispecific T-cell engager blinatumomab is effective, safe and tolerable in the treatment of patients with relapsed/refractory B-precursor ALL.
详细描述
Relapsed/refractory B-precursor ALL in adult patients is an aggressive malignant disease with dismal prognosis and unmet medical need. Additional therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. The purpose of this study is to investigate the efficacy, safety and tolerability of different doses of the bispecific T-cell engager blinatumomab in adult patients with relapsed/refractory B-precursor ALL. Patrticipants will receive up to five 4-week cycles of intravenous blinatumomab treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Patients with B-precursor ALL relapsed after at least induction and consolidation or having refractory disease
- •More than 5% blasts in bone marrow
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Life expectancy of ≥ 12 weeks
排除标准
- •History or presence of clinically relevant central nervous system (CNS) pathology
- •Infiltration of cerebrospinal fluid (CSF) by ALL
- •Autologous/allogeneic hematopoietic stem cell transplantation (HSCT) within six weeks/three months prior to start of blinatumomab treatment
- •Active Graft-versus-Host Disease (GvHD)
- •Patients with Philadelphia chromosome (Ph)+ ALL eligible for treatment with dasatinib or imatinib
- •Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
- •Immunotherapy (e.g. rituximab) within four weeks prior to start of blinatumomab treatment
- •Infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
- •Pregnant or nursing women
- •Previous treatment with blinatumomab
结局指标
主要结局
Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment
时间窗: Within the first 2 cycles of treatment, 12 weeks
At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria: Complete Response/Remission (CR): * Less than or equal to 5% blasts in the bone marrow * No evidence of circulating blasts or extramedullar disease * Full recovery of peripheral blood counts: * Platelets \> 100,000/μL * Hemoglobin ≥ 11 g/dL * Absolute neutrophil count (ANC) \> 1,500/μL Complete Remission with only Partial Hematological Recovery (CRh\*): * Less than or equal to 5% blasts in the bone marrow * No evidence of circulating blasts or extramedullar disease * Partial recovery of peripheral blood counts: * Platelets \> 50,000/μL * Hemoglobin ≥ 7 g/dL * ANC \> 500/μL.
次要结局
- Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment(Within the first 2 cycles of treatment, 12 weeks)
- Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab(Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days)
- Percentage of Participants With a Minimal Residual Disease (MRD) Response During the Core Study(During the core study treatment period (up to 30 weeks).)
- Steady State Blinatumomab Concentration(Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.)
- Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment(Within the first 2 cycles of treatment, 12 weeks)
- Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment(Within the first 2 cycles of treatment, 12 weeks)
- Time to Hematological Relapse(Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.)
- Serum Cytokine Peak Levels(Samples were collected prior to treatment start (baseline), and at 2, 6, 24, and 48 hours after drug infusion start, and at these same time points when dose is escalated in each treatment cycle.)
- Relapse-free Survival(Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.)
- Number of Participants With Treatment-emergent Adverse Events(From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle; median treatment duration was 55.7 days.)
- Clearance of Blinatumomab(Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.)
- Overall Survival(Up to the data cut-off date of 15 October 2012; maximum follow up time was 667 days.)