NCT03516760终止1 期
A Multicenter, Open-label, Dose-escalating, Phase I Trial With GEM333, a CD33 Targeted Bispecific Antibody Engaging T-cells, in Relapsed or Refractory Acute Myeloid Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 36
- 试验地点
- 7
- 主要终点
- Incidence of dose limiting toxicity (DLT)
研究概览
简要总结
This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug GEM333 in patients with acute myeloid leukemia (AML). This AML was relapsed after previous therapy or was refractory to the standard therapy.
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
- •Male or female patients, ≥ 18 years of age
- •Documented definitive diagnosis of CD33 positive AML (according to standard of care testing) in
- •2a. Patients having received standard induction chemotherapy: either refractory to standard induction treatment, or is relapsed within 6 months after achieving 1st CR, or relapsed later than 6 months after 1st CR and refractory to standard salvage regimen, or relapse after ≥ 2nd CR and not eligible for curative treatment (i.e. allogeneic stem cell transplantation)
- •2b. Patients not eligible for standard induction chemotherapy: either refractory or progressive after at least 1 cycle of demethylating agents
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Life expectancy of at least 2 months
- •Adequate renal and hepatic laboratory assessments:
- •Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of ≥ 45% as assessed by transthoracal two-dimensional echocardiography
- •A female of childbearing potential may be enrolled providing she has a negative pregnancy test at screening visit and is routinely using a highly effective method of birth control (pearl index of ≤ 1 required) resulting in a low failure rate (e.g. hormonal contraception, intrauterine device, total sexual abstinence or sterilization) until 3 months from the last study drug administration. Male patients must also practice a highly effective method of birth control.
- •Able to give written informed consent
- •Weight ≥ 45 kg
排除标准
- •Acute promyelocytic leukemia (t15;17)
- •Manifestation of AML in central nervous system
- •Leukocytosis > 10 Gpt/L
- •Cardiac disease: i.e. heart failure NYHA III or IV; unstable coronary artery disease (Myocardial Infarction more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- •Patients undergoing renal dialysis
- •Pulmonary disease with clinical relevant hypoxia (need for continuous oxygen inhalation)
- •Active central nervous diseases (e.g. parkinson, multiple sclerosis, epilepsy) and stroke within last 6 months
- •Active infectious disease considered by investigator to be incompatible with protocol
- •Allogeneic stem cell transplantation within last three months or GvHD requiring immune-suppressive therapy
- •Major surgery within 28 days prior to start of study medication
- •Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
- •Checkpoint inhibitors und CD33 targeting agents within 8 weeks prior to start of trial medication
- •Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants
- •Treatment with any investigational drug substance or experimental therapy within 4 weeks prior to start of trial medication or 5 half lives of the substance prior to start of trial medication
- •Pregnant or breastfeeding women
- •Psychologic disorders, drug and/or significant active alcohol abuse
- •Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
- •Known hypersensitivity to GEM333 excipients
- •Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
- •Incapability of understanding purpose and possible consequences of the trial
- •Patients who should not be included according to the opinion of the investigator
研究组 & 干预措施
GEM333
Experimental
application of GEM333, a CD33 targeted bispecific antibody engaging T-cells
干预措施: GEM333 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicity (DLT)
时间窗: End of Treatment (EOT) +8 days resp. +28 days
Dose Limiting Toxicity is defined as any event at least possibly related to IMP (complete definition provided protocol)
Incidence and intensity of adverse events graded according to CTCAE V4.03
时间窗: End of Treatment (EOT) +8 days resp. +28 days
Maximum tolerated dose (MTD)
时间窗: End of Treatment (EOT) +8 days resp. +28 days (DLT period)
MTD is the previous dose level of the cohort where a DLT is observed in at least wo subjects.
次要结局
- Composite complete remission (CRc) rate(until two years after start of study medication)
- Overall survival(until two years after start of study medication)
- Complete remission (CR)(until two years after start of study medication)
- Partial Remission (PR)(until two years after start of study medication)
- Best response rate(until two years after start of study medication)
- Recommended phase 2 dose(From start of treatment until up to +28 days after last treatment cycle (1 initial cycle + max. 2 additional cycles per patient). Each cycle consists of 10 days treatment plus DLT evaluation period (8 resp. 28 days, depending on blast clearance).)
- Disease stabilization (DS)(until two years after start of study medication)
- Duration of CRc(until two years after start of study medication)
- Duration of PR(until two years after start of study medication)
- Progression free survival (PFS)(until two years after start of study medication)
研究者
研究点 (7)
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