A Phase 1b Open-label Study to Investigate Safety, Tolerability and Pharmacokinetics of Intravenous Blinatumomab in Japanese Adult Subjects With Newly Diagnosed Philadelphia-negative B-precursor Acute Lymphoblastic Leukemia (B-ALL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The main objective of the study is to evaluate safety and tolerability of blinatumomab in adult Japanese participants with newly diagnosed B-ALL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Japanese adult participants ≥ 18 years and ≤ 70 years at enrollment.
- •Participant should have newly diagnosed B-cell precursor (BCP)
- •Philadelphia-negative ALL in CR/CRh after induction/consolidation therapy with any MRD (+ or -).
- •CR/CRh as defined in Section 11.10, Appendix 10 after induction and at any time during consolidation chemotherapy with ALL MRD2008/2019/2023 protocol regimen or 3 blocks of Hyper-CVAD.
- •Bone marrow function as defined below:
- •Absolute neutrophil count (ANC) (Neutrophils) ≥500/μL
- •Platelets ≥50.000/μL (transfusion permitted)
- •Adequate renal and hepatic function:
- •Total bilirubin (TBL) ≤ 2.0 x upper limit of normal (ULN) (ULN; unless Gilbert's Disease or if liver involvement with leukemia)
- •Creatinine clearance ≥50 mL/min/1.73 m^2
- •Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.
排除标准
- •Disease Related
- •Current infiltration of cerebrospinal fluid (CSF) by ALL. If screening CSF demonstrates leukemic blasts, participants must receive intrathecal treatment and demonstrate negative CSF before enrollment and starting blinatumomab infusion.
- •Immunotherapy (eg, rituximab, alemtuzumab) within 4 weeks before start of protocol-specified therapy.
- •Other Medical Conditions
- •History of relevant central nervous system (CNS) pathology or current relevant CNS pathology (e.g., seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or coordination or movement disorders).
- •Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
- •Active uncontrolled infection requiring therapy.
- •History of other malignancy within the past 3 years, with the following exceptions:
- •Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
- •Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease.
- •Adequately treated cervical carcinoma in situ without evidence of disease.
- •Adequately treated breast ductal carcinoma in situ without evidence of disease.
- •Prostatic intraepithelial neoplasia without evidence of prostate cancer.
- •Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
- •Prior/Concomitant Therapy
- •Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis)
- •Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus. In Japan, follow the JSH Guidelines for the Management of Hepatitis B Virus Infection version 4 (The Japan Society of Hepatology, 2022) for the screening of Hepatis B virus infection.
- •Radiotherapy within 4 weeks prior to study treatment.
- •Prior/Concurrent Clinical Study Experience
- •Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). This does not apply to other investigational procedures or participation in observational research studies while participating in this study are excluded.
- •Other Exclusions
- •Participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment and for an additional 48 hours after the last dose of blinatumomab.
- •Participants who are breastfeeding or who plan to breastfeed while on study through 48 hours after the last dose of blinatumomab.
- •Participants planning to become pregnant or donate eggs while on study through 48 hours after the last dose of blinatumomab.
- •Participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive urine or serum pregnancy test.
- •Participant has known hypersensitivity to blinatumomab or to any component of the product formulation.
- •Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g., Clinical Outcome Assessments) to the best of the participant and investigator's knowledge.
- •History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety, or interfere with the study evaluation, procedures, or completion.
研究组 & 干预措施
Blinatumomab
Participants affected by B-ALL will receive blinatumomab as an intravenous (IV) infusion.
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to approximately 31 weeks
An adverse event (AE) is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurred after the participant received study treatment. A serious AE (SAE) is defined as any untoward medical occurrence that is: immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect.
Number of Participants Experiencing Adverse Events of Interest (EOI)
时间窗: Up to 31 weeks
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-related TEAEs
时间窗: From first dose until 33 days after last dose of trial; median (min,max) overall duration was 107.4 (41.2, 190.2) days
An adverse event (AE) was any untoward medical occurrence in a clinical trial participant irrespective of a causal relationship with the trial treatment. TEAEs are any events that occurred after the participant received trial treatment. A serious TEAE was defined as any untoward medical occurrence that: was immediately life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was any other medically important serious event. Treatment-related TEAEs were any AEs that could be considered attributable to the trial treatment.
Number of Participants Experiencing Adverse Events of Interest (EOI)
时间窗: From first dose until 33 days after last dose of trial; median (min,max) overall duration was 107.4 (41.2, 190.2) days
An AE was any untoward medical occurrence in a clinical trial participant irrespective of a causal relationship with the trial treatment. TEAEs were any events that occurred after the participant received trial treatment.
次要结局
- Steady-state Concentration (Css) of Blinatumomab(Day 1 pre-dose, 2 and 6 hours post-dose on Day 1, Day 2, Day 3, Day 29)
- Clearance (CL) of Blinatumomab(Day 1 pre-dose, 2 and 6 hours post-dose on Day 1, Day 2, Day 3, Day 29)
- Number of Participants Achieving Minimal Residual Disease (MRD) After Each Cycle of Blinatumomab(Cycles 1-4: Day 29 (each cycle is 6 weeks))
- Number of Participants Achieving Hematologic Complete Remission (CR)(Cycles 1-4: Day 29 (each cycle is 6 weeks))
- Number of Participants Achieving Hematologic CR with Partial Peripheral Count Recovery (CRh)(Cycles 1-4: Day 29 (each cycle is 6 weeks))
- Steady-state Concentration (Css) of Blinatumomab(Cycle 1: Day 1 pre-dose, 2 and 6 hours post-dose on Day 1, Day 2, Day 3, Day 29; Cycle 2: Day 1 pre-dose, and Days 2 and 29; Cycles 3 and 4: Day 1 pre-dose, and Day 29)
- Clearance (CL) of Blinatumomab(Cycle 1: Day 1 pre-dose, 2 and 6 hours post-dose on Day 1, Day 2, Day 3, Day 29; Cycle 2: Day 1 pre-dose, and Days 2 and 29; Cycles 3 and 4: Day 1 pre-dose, and Day 29)
- Number of Participants Achieving Minimal Residual Disease (MRD) After Each Cycle of Blinatumomab(Cycles 1-4: Day 29 (each cycle is 42 days))
- Number of Participants Achieving Hematologic CR(Cycles 1-4: Day 29 (each cycle is 42 days))
- Number of Participants Achieving Hematologic CR With Partial Peripheral Count Recovery (CRh)(Cycles 1-4: Day 29 (each cycle is 42 days))