NCT07223190尚未招募3 期
A Phase 3, Open-label, Randomized, Controlled Trial of Subcutaneous Versus Intravenous Blinatumomab in Newly Diagnosed Adults With Philadelphia Chromosome Negative B-cell Precursor Acute Lymphoblastic Leukaemia
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- Amgen
- 入组人数
- 560
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The main objective of this trial is to demonstrate that subcutaneous (SC) blinatumomab in conjunction with chemotherapy (Arm B) is non-inferior to continuous intravenous infusion (cIV) blinatumomab in conjunction with chemotherapy (Arm A) in overall survival (OS) in newly diagnosed participants with Philadelphia chromosome (Ph) negative B-cell precursor acute lymphoblastic leukemia (B-ALL) who are in complete remission (CR) or CR with incomplete peripheral count recovery (CRi) after induction.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL).
- •Age ≥18 years old.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤2, higher ECOG score allowed if due to underlying leukemia.
- •Adequate organ function as described below:
- •Renal: estimated glomerular filtration rate (GFR) ≥30 mL/min/1.73m^2 per the Modification of Diet in Renal Disease for adult participants equation
- •Hepatic function: total bilirubin ≤3.0 mg/dL prior to start of treatment; unless due to Gilbert's Disease or if liver involvement with leukemia
- •Cardiac: left ventricular ejection fraction (LVEF) ≥50% and no clinically significant, uncontrolled, or active cardiovascular, cerebrovascular, or peripheral vascular disease, or history of or active venous thromboembolism (VTE) disease.
排除标准
- •Other Medical Conditions
- •Isolated extramedullary disease.
- •History or presence of clinically relevant central nervous system (CNS) pathology or event such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis.
- •Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
- •History of other malignancy within the past 3 years, except for malignancy treated with curative intent with low risk for recurrence. Exceptions include:
- •Adequately treated non-melanoma 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.
- •Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B or hepatitis C virus.
- •Participant with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.
- •Prior/Concomitant Therapy • Prior cancer chemotherapy/immunotherapy for this newly diagnosed B-ALL before the start of protocol-required therapy with the exception of intrathecal (IT) chemotherapy or pre-phase chemotherapy. Localized radiation for pain or disease control is allowed.
- •Prior/Concurrent Clinical Trial Experience
- •Currently receiving a trial intervention, or less than 30 days or 5 half-lives if known (whichever is later) since ending a trial intervention in another investigational device or drug trial.
- •Other Exclusions
- •History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety.
- •Female participants of childbearing potential unwilling to use contraception.
- •Female participants who are breastfeeding or who plan to breastfeed.
- •Female participants planning to become pregnant or donate eggs.
- •Female participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive urine or serum pregnancy test.
- •Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception.
- •Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom.
- •Male participants unwilling to abstain from donating sperm.
- •Participant has known sensitivity to any of the products or components to be administered during dosing.
- •Participant considered unlikely to be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the participant and investigator's knowledge; exception - unavailability of a patient-reported outcome (PRO) in the participants' preferred/native language is not prohibitive to enrollment for eligible participants.
研究组 & 干预措施
HyperCVAD + cIV Blinatumomab in Consolidation
Active Comparator
Participants with Ph-negative B-ALL will receive cIV blinatumomab infusion for cycles 1, 2, 5 and 6 (each cycle will be 35 days), in conjunction with chemotherapy (HyperCVAD) for cycles 3, 4, 7 and 8 (each cycle will be 2-4 weeks).
干预措施: Blinatumomab (Drug)
HyperCVAD + SC Blinatumomab in Consolidation
Experimental
Participants with Ph-negative B-ALL will receive SC injections of blinatumomab for cycles 1, 2, 5 and 6 (each cycle will be 35 days), in conjunction with chemotherapy (HyperCVAD) for cycles 3, 4, 7 and 8 (each cycle will be 2-4 weeks).
干预措施: HyperCVAD (Drug)
HyperCVAD + cIV Blinatumomab in Consolidation
Active Comparator
Participants with Ph-negative B-ALL will receive cIV blinatumomab infusion for cycles 1, 2, 5 and 6 (each cycle will be 35 days), in conjunction with chemotherapy (HyperCVAD) for cycles 3, 4, 7 and 8 (each cycle will be 2-4 weeks).
干预措施: HyperCVAD (Drug)
HyperCVAD + SC Blinatumomab in Consolidation
Experimental
Participants with Ph-negative B-ALL will receive SC injections of blinatumomab for cycles 1, 2, 5 and 6 (each cycle will be 35 days), in conjunction with chemotherapy (HyperCVAD) for cycles 3, 4, 7 and 8 (each cycle will be 2-4 weeks).
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to 5 years from randomization
次要结局
- Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs)(Up to 5 years from randomization)
- Area Under the Concentration-time Curve in Cycle 1 (AUCcycle 1) for SC Blinatumomab(Up to Cycle 1 Day 35 (Cycle length = 35 days))
- AUCcycle 1 for cIV Blinatumomab(Up to Cycle 1 Day 35 (Cycle length = 35 days))
- Average Concentration Following Cycle 1 Day 19 Dosing (Cavgd19dose) for SC Blinatumomab(From predose on Cycle 1 Day 19 to predose on Cycle 1 Day 22 (Cycle length = 35 days))
- Steady-state Concentration (Css) for cIV Blinatumomab(Up to Cycle 1 Day 29 (Cycle length = 35 days))
- Relapse-free Survival (RFS)(Up to 5 years from randomization)
- Number of Participants With CR With MRD Response(Up to 5 years from randomization)
- Number of Participants With Deep CR With MRD Response(Up to 5 years from randomization)
- Change from Day 1 Consolidation Cycle 1 to End of Consolidation in Role Functioning as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)(Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days))
- Change from Day 1 Consolidation Cycle 1 to End of Consolidation in Overall Quality of Life as Measured by EORTC QLQ-C30(Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days))
- Change from Day 1 Consolidation Cycle 1 to End of Consolidation in All Other Domains/Items as Measured by EORTC QLQ-C30(Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days))
- Change From Day 1 Consolidation Cycle 1 to End of Consolidation in the Visual Analogue Scale (VAS)(Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days))
- Percentage of Time on Treatment With High Side Effect Bother From Consolidation Cycle 1 to End of Consolidation(Consolidation Cycle 1 up to Day 8 and then weekly until end of Consolidation Cycle (Cycle length = 35 days))
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