NCT00002765已完成1 期
PHASE I STUDY OF ANTI-TAC(Fv)-PE38 (LMB-2), A RECOMBINANT SINGLE-CHAIN IMMUNOTOXIN FOR TREATMENT OF TAC-EXPRESSING MALIGNANCIES
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 2
研究概览
简要总结
RATIONALE: Immunotoxins can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of LMB-2 immunotoxin in treating patients who have leukemia or lymphoma.
详细描述
OBJECTIVES:
- Assess the therapeutic efficacy and toxicity of the recombinant immunotoxin LMB-2, an anti-Tac murine monoclonal antibody fragment conjugated to a truncated portion of Pseudomonas exotoxin, in patients with Tac-expressing leukemias and lymphomas.
- Define the pharmacokinetics of LMB-2, including the terminal elimination serum half-life, area under the curve, and volume of distribution.
- Evaluate, in a preliminary manner, the immunogenicity of LMB-2 in these patients.
- Determine the effect of LMB-2 on various components of the circulating cellular immune system.
OUTLINE: This is a dose escalation study.
Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 15-21 days for up to 10 courses in the absence of disease progression, neutralizing antibodies, or unacceptable toxicity.
Cohorts of 3-6 patients each receive escalating doses of LMB-2 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 patient experiences dose limiting toxicity.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed Hodgkin's disease, non-Hodgkin's lymphoma, or leukemia in one of the following categories:
- •Adult T-cell leukemia or lymphoma (ATL)
- •No smoldering ATL
- •No limitation on prior therapy
- •Cutaneous T-cell lymphoma (CTCL)
- •Stages IB-III and failed at least 1 standard therapy
- •Stage IV regardless of prior therapy
- •Stages I-IV peripheral T-cell lymphoma
- •Relapsed after standard chemotherapy
- •Ineligible for or refused salvage chemotherapy or bone marrow transplantation (BMT)
- •B-cell non-Hodgkin's lymphoma (NHL) of any histology
- •Indolent stages II-IV NHL
- •Failed at least 1 standard therapy
- •Disease symptomatic and requiring treatment
- •Aggressive NHL
- •Relapsed after standard chemotherapy
- •Ineligible for or refused salvage chemotherapy or BMT
- •Chronic lymphocytic leukemia (CLL)
- •Rai stages III and IV or Binet stage C
- •Failed standard therapy and at least 1 salvage chemotherapy
- •Primary B-cell prolymphocytic leukemia or prolymphocytic transformation of CLL
- •Failed standard therapy and at least 1 salvage chemotherapy
- •Hairy cell leukemia
- •Failed standard and salvage chemotherapy
- •Ineligible for or refused further salvage chemotherapy or BMT
- •Acute myelogenous leukemia
- •Failed standard chemotherapy
- •Ineligible for or refused salvage chemotherapy or BMT
- •Stages II-IV Hodgkin's disease
- •Failed standard chemotherapy
- •Ineligible for curative salvage radiotherapy or chemotherapy
- •Ineligible for or refused BMT
- •Patients with leukemias or lymphomas not easily classified in above categories who have failed standard therapy and are ineligible for or have refused bone marrow transplant
- •Evidence of interleukin-2 receptor-alpha (IL2Ra) expression by one of the following:
- •Greater than 10% of malignant cells reactive with anti-Tac by immunohistochemistry
- •Greater than 10% of malignant cells from a particular site positive by FACS
- •Greater than 400 IL2Ra sites per malignant cell by radiolabeled anti-Tac binding
- •Soluble IL2Ra level greater than 1,000 U/mL (normal geometric mean 235, with 95% confidence levels of 112-502 U)
- •Hodgkin's disease with measurable disease not amenable to biopsy
- •No CNS disease requiring treatment
- •Malignant cells in CSF allowed if judged not to represent clinically significant leukemic or lymphomatous meningitis (as in CSF contamination by blood)
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 50-100%
- •Life expectancy:
- •Greater than 2 months
- •Hematopoietic:
- •Absolute neutrophil count greater than 1,000/mm3*
- 另有 28 项未显示
排除标准
- 未提供
研究者
研究点 (2)
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