A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Adults with Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- Amgen K.K.
- 入组人数
- 125
- 主要终点
- Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs)
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
- 分配方式
- Non-randomized Controlled Trial
- 干预模型
- Single Assignment
- 主要目的
- Treatment Purpose
- 盲法
- Open(masking Not Used)
入排标准
- 年龄范围
- 18age old over 至 No limit（—）
- 性别
- All
入选标准
- •Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
- •Participants with B-precursor ALL with any of the following:
- •Either refractory to primary induction therapy or refractory to at least 1 salvage therapy OR
- •In untreated first, second, third or greater relapse or refractory relapse
- •First Relapse is defined as achievement of first Complete Remission (CR) [CR1] during upfront therapy then relapse during or after continuation therapy
- •Primary Refractory disease is defined as the absence of CR after standard induction therapy
- •Refractory relapse is defined as lack of CR after salvage treatment
- •Second relapse or later relapse is defined as relapse after achieving a second CR (CR2) in first or later salvage
- •Refractory to salvage is defined as no attainment of CR after salvage
- •Relapsed or Refractory at any time after first salvage therapy.
- •Relapse at any time after allogenic hematopoietic stem cell transplant (HSCT).
- •Greater than or equal to 5% blasts in the Bone Marrow (Exception: Isolated Non-central nervous system (CNS) extramedullary disease [EMD]).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to
- •Participants with relapse or refractory B Cell ALL Ph+ disease and that are intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
- •The above is a summary, other inclusion criteria details may apply.
排除标准
- •Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia.
- •History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (>= grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
- •Isolated Extramedullary (EM) Disease
- •Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
- •Testicular leukemia
- •History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
- •Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
- •Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
- •Immunotherapy within 4 weeks before start of protocol-specified therapy. Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed, if treatment ended more than 4 weeks prior to start of protocol therapy and no prior CNS complications.
- •Currently receiving treatment in or less than 30 days or 5 half-lives since ending treatment on another investigational study(ies).
- •Abnormal screening laboratory parameters.
- •Female participant: Expected to breastfeed during treatment and for 96 hours after the last dose of investigational product (SC blinatumomab).
- •The above is a summary, other exclusion criteria details may apply.
结局指标
主要结局
Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs)
时间窗: Up to 29 days
Number of participants who experience dose limiting toxicities (DLTs)
Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
时间窗: Up to approximately 28 weeks
Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
Dose Escalation Phase: Number of participants who experience one or more serious TEAEs
时间窗: Up to approximately 28 weeks
Number of participants who experience one or more serious TEAEs
Dose Escalation Phase: Number of participants who experience one or more treatment-related treatment-emergent adverse events
时间窗: Up to approximately 28 weeks
Number of participants who experience one or more treatment-related treatment-emergent adverse events
Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs) of Interest (AEIs)
时间窗: Up to approximately 28 weeks
Number of participants who experience one or more adverse events (AEs) of Interest (AEIs)
Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission (CR)
时间窗: Up to 68 days
Number of participants who achieve complete remission (CR)
Dose Expansion Phase (R/R B-ALL): Number of participants who achieve complete remission with partial hematological recovery (CRh)
时间窗: Up to 68 days
Number of participants who achieve complete remission with partial hematological recovery (CRh)
Phase 2 Ph-IIC: Maximum concentration (Cmax) of blinatumomab SC1 and SC2
时间窗: Up to approximately 4 weeks
Maximum concentration (Cmax) of blinatumomab SC1 and SC2
Phase 2 Ph-IIC: Average concentration (Cavg) of blinatumomab SC1 and SC2
时间窗: Up to approximately 4 weeks
Average concentration (Cavg) of blinatumomab SC1 and SC2
Phase 2 Ph-IIC: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2
时间窗: Up to approximately 4 weeks
Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2
Phase 2 Ph-IIC: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2
时间窗: Up to approximately 4 weeks
Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2
次要结局
未报告次要终点