A Phase 1, Open Label, Dose Escalation, and Dose Expansion Study to Assess the Safety, Tolerability, and Preliminary Antileukemic Activity of GDX012 in Patients With Minimal Residual Disease (MRD) Positive Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Establish the maximum tolerated dose (MTD) of GDX012
研究概览
简要总结
The purpose of this first-in-human study is to assess the safety, tolerability, antileukemic activity and maximum tolerated dose (MTD) of GDX012 in AML patients who are MRD positive by multiparametric flow cytometry.
The study will consist of a dose escalation stage to evaluate various doses of GDX012 after a lymphodepletion regimen comprising fludarabine and cyclophosphamide. Following determination of the MTD of GDX012, the study will expand at the MTD. Patients will be followed up for 12 months, after receiving GDX012.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •≥ 18 years old
- •Weight ≥ 40 kg
- •Anticipated life expectancy > 3 months prior to lymphodepletion
- •Karnofsky Performance Score ≥ 70%
- •Histologically confirmed diagnosis of AML
- •In complete response (CR) (including CRi/CRp); patients in first, second or subsequent CR (including CRi/CRp) are permitted
- •MRD detected in bone marrow by MFC
- •Negative pregnancy test (females of childbearing potential only)
- •Agree to use effective birth control
- •Left ventricular ejection fraction (LVEF) ≥ 50%
- •Platelet Count ≥ 20 x 109/L
- •Prothrombin Time or INR ≤ 1.5 x ULN (unless receiving therapeutic anticoagulation)
- •Partial Thromboplastin Time ≤ 1.5 x ULN (unless receiving therapeutic anticoagulation)
- •Hemoglobin ≥ 8.0 g/dL
- •Creatinine Clearance ≥ 40mL/min
- •Serum Total Bilirubin ≤ 1.5 x ULN (unless documented Gilbert's Syndrome with Direct Bilirubin < 35% of Total Bilirubin)
- •ALT ≤ 2.5 x ULN
排除标准
- •Cytotoxic chemotherapy within 3 weeks
- •Immune therapy within 4 weeks
- •Immunosuppressive therapy within 2 weeks (with exceptions)
- •Investigational treatment or interventional clinical trial within 4 weeks or 5 half-lives (if known), whichever is longer
- •Major surgery within 4 weeks and/or not fully recovered from surgery-related toxicities
- •Known hypersensitivity to chemotherapy, other agents, or excipients used in this study
- •Female patient that is pregnant or lactating/breastfeeding
- •Ongoing toxicity from prior anti-cancer therapy that have not recovered to ≤ Grade 1 (with exceptions)
- •History of chronic or recurrent autoimmune or immune-mediated disease requiring steroids or other immunosuppressive treatments (including anti-tumor necrosis factor agents)
- •Active CNS involvement (i.e. leukemic infiltration)
- •Any other malignancy that requires active therapy
- •Uncontrolled intercurrent illness (i.e. acute coronary syndrome in the last 6 months)
- •Active infection with HIV, Hepatitis B or Hepatitis C
- •NOTE: other protocol defined inclusion/exclusion criteria may apply.
结局指标
主要结局
Establish the maximum tolerated dose (MTD) of GDX012
时间窗: Up to 100 days
Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs)
时间窗: Up to 100 days
AEs and SAEs occurring following administration of GDX012
Incidence of treatment emergent clinically significant abnormal laboratory assessments
时间窗: Up to 100 days
Standard clinical laboratory assessments for organ function (i.e. heart, kidney, liver)
Incidence of dose limiting toxicities (DLTs)
时间窗: Up to 100 days
DLTs occurring following administration of GDX012, measured using CTCAE 5.0 criteria
次要结局
- Evaluate the antileukemic activity of GDX012(Up to 1 year)