Phase I Open Label, Single Arm Escalation Trial to Evaluate the Biodistribution and Safety of BU-12 in Patients With Advanced Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Biodistribution of indium-111 BU-12
研究概览
简要总结
RATIONALE: Radiolabeled monoclonal antibodies can find cancer cells and carry cancer-killing substances to them without harming normal cells. This may be effective treatment for leukemia.
PURPOSE: This phase I trial is studying the best dose of yttrium Y 90-labeled monoclonal antibody BU-12 in treating patients with advanced relapsed or refractory acute lymphoblastic leukemia or chronic lymphocytic leukemia.
详细描述
OBJECTIVES:
Primary
- To determine the biodistribution of indium-111 BU-12 in patients with refractory CD19+ leukemia.
Secondary
- To determine the maximum tolerated dose of yttrium Y 90 anti-CD19 antibody BU-12
- Determine the human anti-mouse antibody (HAMA) response.
- To define, preliminarily, the antitumor activity of yttrium Y 90 anti-CD19 antibody BU-12.
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
- •Histologically confirmed CD19-positive (> 25% by flow cytometry evaluation of bone marrow blasts) disease of 1 of the following types:
- •Primary refractory or relapsed acute lymphoblastic leukemia (ALL) defined as persistent disease following a minimum of two different standard effective chemotherapy induction attempts at time of diagnosis or at relapse
- •Chronic Lymphocytic leukemia (CLL) following blast crisis (≥15% bone marrow blasts following a minimum of one standard effective chemotherapy induction attempt)
- •Human anti-mouse antibody (HAMA) must be negative
- •Patients who have relapsed ≥ 60 days following an autologous or allogeneic transplant are eligible if all other eligibility criteria are met
- •No active central nervous system (CNS) disease
- •ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
- •Life expectancy > 8 weeks
- •Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •LVEF ≥ 45% by MUGA/ECHO
- •Oxygen saturation on room air > 92% and no oxygen requirement
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients mus use effective contraception
排除标准
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to of yttrium Y 90 anti-CD19 antibody BU-12 or other agents used in study
- •Uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness/social situations that would limit compliance with study requirements
- •HIV-positive
- •Active graft-vs-host disease
- •Less than 4 weeks since prior agents and recovered
- •Less than 7 days since prior therapy with any biologic agent, defined as a growth factor or cytokine
- •Less than 3 months since prior antibody or biologic anticancer therapy (e.g., alemtuzumab or epratuzumab)
- •Other concurrent investigational agents
- •Patients with peripheral blasts > 5,000/uL may receive concurrent hydroxyurea
研究组 & 干预措施
111 In-BU-12
111In-BU-12 is the 111Indium-labeled murine monoclonal antibody used for imaging and dosimetry.
干预措施: yttrium Y 90 anti-CD19 monoclonal antibody BU12 (Radiation)
111 In-BU-12
111In-BU-12 is the 111Indium-labeled murine monoclonal antibody used for imaging and dosimetry.
干预措施: 111In-BU-12 (Radiation)
结局指标
主要结局
Biodistribution of indium-111 BU-12
时间窗: Immediately post infusion, 4-6 hours after infusion and Days 1, 3, 4 and 7 after infusion
Perform a whole body scan acquiring both anterior and posterior images at a speed of 10 cm/min (20 minute scan) using a medium energy collimator, a 256 x 1024 computer acquisition matrix and acquisition photo peak settings of 172 and 247 keV with 15% windows.
次要结局
- Presence or absence of a human antibody to murine antibody(baseline, 28 and 60 days post therapy, and at 6 months post therapy)
- Maximum tolerated dose of yttrium Y 90 anti-CD19 antibody BU-12(Beginning Day 1 of treatment)
- Number of Patients by Clinical Response(day 28 and day 60)
- Time to Clinical Response(Day 28, 60, 6 Months)