Phase Ib/II Study Assessing the Clinical Activity and Safety of Brexucabtagene Autoleucel as a Consolidation in Patients With Relapsed/Refractory (R/R) and Newly Diagnosed B-cell Acute Lymphocytic Leukemia (ALL) Post Cytoreduction With Mini-HCVD-inotuzumab-blinatumomab/HCVAD-inotuzumab-blinatumomab
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety and adverse events (AEs)
研究概览
简要总结
To learn about the safety of giving the drug brexucabtagene autoleucel to participants with relapsed/refractory B-cell ALL after treatment with inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD. Also, to learn if giving brexucabtagene autoleucel to patients with relapsed/refractory or high-risk, newly diagnosed B-cell ALL after treatment with inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD can help to control the disease.
详细描述
Primary Objectives:
To assess the Efficacy of Brexucabtagene autoleucel [anti-CD19 autologous derived chimeric antigen receptor T-cell (CAR-T)] in terms of EFS in patients with R/R and high-risk newly diagnosed B-cell acute lymphoblastic leukemia (B-cell ALL) post cytoreduction with mini-hyper-CVD-inotuzumab-blinatumomab/Hyper-CVAD-inotuzumab-blinatumomab
The EFS will be estimated in terms of median EFS and 9-month EFS for the R/R cohort and 18-month EFS for the frontline cohort.
Secondary Objectives:
- 12 and 24-months overall survival (OS): 12 months for the R/R cohort and 24 months for the frontline cohort
- Duration of persistent MRD negativity by flow cytometry and NGS at 9 and 18 months: 9 months for the R/R cohort and 18 months for the frontline cohort
- Best Ooverall response rates [complete remission (CR) and CR with incomplete count recovery (CRi)]
- Achievement of MRD negativity amongst patients in CR and not MRD negative before Brexucabtagene autoleucel infusion
- Safety
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants of age ≥18 years with documented relapsed or refractory B-cell ALL
- •In the newly diagnosed cohort: Participants of age ≥18 years with high-risk newly diagnosed B-cell ALL defined as:
- •KMT2A rearranged ALL
- •Complex cytogenetics as per NCCN 2022
- •Low-hypodiploidy/tetraploidy
- •Philadelphia-like ALL (based on CRLF2 overexpression or recurrent Ph-like genetic fusions)
- •Performance status of 0, 1, or 2
- •Adequate organ function with creatinine less than or equal to 1.6 mg/dl, bilirubin less than or equal to 3.5 mg and ALT and AST less than or equal to 5 times institutional upper limit of normal
- •Participants should be CD19 expression positive (>50%) before enrollment
- •Participants with chronic viral infections like Hepatitis B-virus, Hepatitis C virus or Human Immunodeficiency virus I/II will be eligible if they are on therapy and infections are under control.
排除标准
- •Philadelphia positive B-cell ALL
- •Pregnant or lactating; women of child-bearing potential (WOCBP) must have negative pregnancy test. WOCBP defined as not post-menopausal for 12 months or no previous surgical sterilization
- •Prior exposure to brexu-cel or other anti-CD-19 CAR T cell therapy
- •Active and uncontrolled disease/infection as judged by the treating physician
- •Unable or unwilling to sign the consent form
- •No other investigational therapy within the past 14 days
研究组 & 干预措施
Phase 1B + Phase 2
Participants found to be eligible to take part in this study, you will be assigned to a study phase (Phase 1B or Phase 2). Up to 10 participants will be enrolled in Phase 1B, and up to 30 will be enrolled in Phase 2. All participants will first receive cytoreductive therapy (inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD), followed by lymphodepletion chemotherapy and 1 dose of brexucabtagene autoleucel.
干预措施: Blinatumomab (Drug)
Phase 1B + Phase 2
Participants found to be eligible to take part in this study, you will be assigned to a study phase (Phase 1B or Phase 2). Up to 10 participants will be enrolled in Phase 1B, and up to 30 will be enrolled in Phase 2. All participants will first receive cytoreductive therapy (inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD), followed by lymphodepletion chemotherapy and 1 dose of brexucabtagene autoleucel.
干预措施: Inotuzumab Ozogamicin (Drug)
Phase 1B + Phase 2
Participants found to be eligible to take part in this study, you will be assigned to a study phase (Phase 1B or Phase 2). Up to 10 participants will be enrolled in Phase 1B, and up to 30 will be enrolled in Phase 2. All participants will first receive cytoreductive therapy (inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD), followed by lymphodepletion chemotherapy and 1 dose of brexucabtagene autoleucel.
干预措施: Hyper-CVAD (Drug)
Phase 1B + Phase 2
Participants found to be eligible to take part in this study, you will be assigned to a study phase (Phase 1B or Phase 2). Up to 10 participants will be enrolled in Phase 1B, and up to 30 will be enrolled in Phase 2. All participants will first receive cytoreductive therapy (inotuzumab ozogamicin, blinatumomab, and either hyper-CVAD or mini-hyper-CVD), followed by lymphodepletion chemotherapy and 1 dose of brexucabtagene autoleucel.
干预措施: Mini-hyper-CVD (Drug)
结局指标
主要结局
Safety and adverse events (AEs)
时间窗: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
次要结局
未报告次要终点