Phase I Open Label, Single Arm, Dose Escalation Trial to Evaluate the Biodistribution and Safety of AHN-12 In Patients With Advanced Leukemia HM2010-05
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Optimal Dose of AHN-12 Non-radiolabeled Antibody
研究概览
简要总结
This study is a single institution phase I study for the treatment of patients with relapsed or refractory leukemia aged 12 years and older using 90Y-AHN-12.
详细描述
A dose escalation schema will be used with the initial patient receiving the current lowest dose of nonradiolabeled AHN-12 (from 0.20 mg/kg to 1.0 mg/kg). If a favorable biodistribution is not achieved and the patient remains negative for HAMA, the infusion may be repeated up to two more times (with a one level increase in nonradiolabeled AHN-12 each time) in an attempt of achieving favorable biodistribution.
In order to achieve the primary objective of identifying the optimal nonradiolabeled dose of AHN-12 antibody for all patients, if the first patient at the current antibody dose does not achieve favorable biodistribution, the next patient(s) will be treated at the next higher dose level.
Patients achieving favorable biodistribution and remaining negative for HAMA will be eligible for the therapeutic component of this trial. Those not meeting these requirements will be taken off study and followed.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have one of the following histologically confirmed CD45+ diseases. If possible, AHN-12 positivity will be confirmed by flow cytometry on a recent bone marrow or a peripheral blood sample, if circulating blasts are present.
- •Acute myelogenous leukemia (AML), primary refractory or relapsed disease
- •Refractory myelodysplastic syndrome (MDS)
- •AML arising from pre-existing MDS, refractory
- •Acute lymphoblastic leukemia (ALL), primary refractory or relapsed disease
- •Chronic myelogenous leukemia (CML) following blast crisis
- •Age ≥ 12 years
- •Karnofsky Performance Status ≥ 60% (16 years and older) or Lansky Play Score ≥ 60 (<16 years)
- •Life expectancy of > 12 weeks in the opinion of the enrolling medical provider
- •Patients must have adequate organ function
- •Human anti-mouse antibody (HAMA) must be negative (perform on all patients regardless of prior therapies).
- •Consent to adequate contraception. The effects of 90Y-AHN-12 on the developing fetus are unknown.
- •Source of allogeneic stem cells must have been identified in event of severe myelosuppression
- •Able to give written consent.
- •Both men and women of all ethnic groups are eligible for this trial.
排除标准
- •Ongoing grade 2 or greater non-hematologic toxicity due to previously administered therapies
- •< 8 days from completion of therapy with any biologic agent
- •Receiving any investigational agents
- •Active central nervous system (CNS) leukemia are excluded from this clinical trial
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-AHN-12 or other agents used in study.
- •Uncontrolled illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the enrolling medical provider.
- •Pregnant and breastfeeding women are excluded from this study because 90Y-AHN-12, being radioactive, as well as high dose chemotherapy and total body irradiation (TBI) have the potential for teratogenic or abortifacient effects.
- •Human immunodeficiency virus (HIV) positive patients:
- •< 60 days since an autologous transplant
- •Bone marrow cellularity <5% (because of concern of myelosuppression)
研究组 & 干预措施
receiving AHN-12 and 90Y-AHN-12
Patients receiving nonradiolabeled cold AHN-12 (.20 mg/kg to 1.0 mg/kg) of at least one dose and up to a total of 3 dosimetry infusions (intervals no sooner than 8 days and up to 21 days).
干预措施: 90Y-AHN-12 (Biological)
结局指标
主要结局
Optimal Dose of AHN-12 Non-radiolabeled Antibody
时间窗: Day 2
doses of nonradiolabeled antibody are specified: 0.20, 0.40, 0.60, 0.80 and 1.00 mg/kg.
次要结局
- Human Anti-Mouse Antibody (HAMA) Response(30 and 90 Days Post Therapy, Then Every 6 Months If Positive)
- Anti-tumor Activity of 90Y-AHN-12(30 and 90 Days Post Therapy)
- Maximum Tolerated Dose (MTD) of 90Y-AHN-12(Within 14 days of achieving favorable biodistribution)