A Phase 1 Multicenter Study Evaluating the Safety and Efficacy of ACE1831, an Allogeneic Anti-CD20 Antibody-Conjugated Gamma Delta T-cell Therapy, in Adult Subjects With Relapsed/Refractory CD20-expressing B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 26
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
ACE1831 is an off-the-shelf, allogeneic gamma delta T (gdT) cell therapy derived from healthy donors, that is under investigation for the treatment of CD20-expressing B-cell malignancies.
The ACE1831-001 study is an open-label, Phase I, first-in-human (FIH) study that aims to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, and efficacy of ACE1831 in patients with CD20-expressing Non-Hodgkin lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •CD20-positive B-cell NHL that is persistent or progressive after having received at least 2 prior systemic therapies per NCCN guidelines
- •At least 1 measurable lesion according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 or subjects with ECOG scores of 2 with a serum albumin of >3.5
- •Adequate hematologic and renal, hepatic, and cardiac function
- •Oxygen saturation via pulse oxygenation ≥ 92% at rest on room air
排除标准
- •Prior treatment with a genetically modified cell therapy product targeting CD20
- •Autologous stem cell transplant within 6 weeks of informed consent or history of allogeneic stem cell transplantation
- •History of central nervous system (CNS) lymphoma or primary CNS lymphoma
- •History or presence of clinically relevant CNS disorder (e.g. epilepsy)
- •Clinically significant active infection
- •Currently active, clinically significant cardiovascular disease
- •Human Immunodeficiency virus (HIV) infection (however, subjects on anti-retroviral therapy for at least 4 weeks and with HIV viral loads of <400 copies/mL are eligible), active hepatitis B infection, or hepatitis C infection
- •History of other malignancies with the exception of certain treated malignancies with no evidence of disease
- •Primary immunodeficiency disorder
- •Pregnant or lactating female
- •Any medical, psychological, familial, or sociological conditions that, in the opinion of the Investigator or Sponsor Medical Monitor, would impair the ability of the subject to receive study treatment, comply with study requirements, or understanding of the informed consent
研究组 & 干预措施
Treatment Group A (ACE1831)
ACE1831 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE1831.
干预措施: Fludarabine (Drug)
Treatment Group A (ACE1831)
ACE1831 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE1831.
干预措施: Cyclophosphamide (Drug)
Treatment Group B (ACE1831 and obinutuzumab)
ACE1831 dose escalation, in combination with obinutuzumab. Lymphodepleting regimen followed by escalating doses of ACE1831, given in combination with obinutuzumab.
干预措施: Cyclophosphamide (Drug)
Treatment Group B (ACE1831 and obinutuzumab)
ACE1831 dose escalation, in combination with obinutuzumab. Lymphodepleting regimen followed by escalating doses of ACE1831, given in combination with obinutuzumab.
干预措施: Fludarabine (Drug)
Treatment Group A (ACE1831)
ACE1831 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE1831.
干预措施: ACE1831 (Drug)
Treatment Group B (ACE1831 and obinutuzumab)
ACE1831 dose escalation, in combination with obinutuzumab. Lymphodepleting regimen followed by escalating doses of ACE1831, given in combination with obinutuzumab.
干预措施: ACE1831 (Drug)
Treatment Group B (ACE1831 and obinutuzumab)
ACE1831 dose escalation, in combination with obinutuzumab. Lymphodepleting regimen followed by escalating doses of ACE1831, given in combination with obinutuzumab.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 1 month
Change from baseline in ECOG status
时间窗: 1 year
Change from baseline clinical laboratory tests results
时间窗: 1 year
Number of subjects with change from baseline clinically significant lab findings by dose level (descriptive)
Change from baseline in vital signs results
时间窗: 1 year
Number of subjects with change from baseline clinical significant vital signs findings by dose level (descriptive)
Incidence of adverse events (AEs), Dose Limiting Toxicities (DLTs), adverse events of special interest (AESIs), and serious adverse events (SAEs)
时间窗: 2 years
Change from baseline in physical examination results
时间窗: 1 year
Number of subject with change from baseline clinically significant physical examination findings by dose level (descriptive)
Change from baseline in urinalysis results
时间窗: 1 year
Number of subjects with change from baseline clinically significant urinalysis findings by dose level (descriptive)
Change from baseline in electrocardiogram (ECG) results
时间窗: 1 month
Number of subjects with change from baseline clinically significant ECG findings by dose level (descriptive)
次要结局
- Objective Response Rate (ORR)(2 years)
- Measure of anti-ACE1831 antibodies after administration(1 month)
- Persistence of ACE1831 after administration(1 month)