Phase I Study of BL22, A Recombinant Immunotoxin for Chronic Lymphocytic Leukemia and CD22+ Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
研究概览
简要总结
RATIONALE: BL22 immunotoxin can find tumor cells and kill them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating patients with refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or non-Hodgkin's lymphoma.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of recombinant BL22 immunotoxin in patients with CD22-positive refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or indolent non-Hodgkin's lymphoma.
- Determine the safety and efficacy of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the immunogenicity of this drug in these patients.
- Determine the effect of this drug on various components of the circulating cellular immune system in these patients.
OUTLINE: This is a nonrandomized, dose-escalation study. Patients are stratified according to disease type (chronic lymphocytic leukemia vs non-Hodgkin's lymphoma).
Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats ≥ every 27 days for up to 6 courses in the absence of neutralizing antibodies to BL22 or PE38, disease progression, or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients who relapse from a CR lasting ≥ 6 months may receive additional courses.
Cohorts of 3-6 patients per stratum receive escalating doses of recombinant BL22 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •DISEASE CHARACTERISTICS:
- •Diagnosis of B-cell leukemia or lymphoma of 1 of the following types:
- •Chronic lymphocytic leukemia
- •Failed standard chemotherapy
- •Prolymphocytic leukemia
- •Failed standard chemotherapy
- •Indolent non-Hodgkin's lymphoma, including mantle cell lymphoma
- •Stage III or IV disease
- •Failed ≥ 1 prior doxorubicin- or fludarabine-containing standard therapy
- •CD22-positive disease, as evidenced by 1 of the following:
- •More than 15% malignant cells react with anti-CD22 by immunohistochemistry
- •More than 30% malignant cells are CD22-positive by fluorescence-activated cell sorting analysis
- •More than 400 CD22 sites per malignant cell (average) by radiolabeled anti-CD22 binding
- •Treatment is medically indicated, as evidenced by any of the following:
- •Progressive disease-related symptoms
- •Progressive cytopenias due to marrow involvement
- •Progressive or painful splenomegaly or adenopathy
- •Rapidly increasing lymphocytosis
- •Autoimmune hemolytic anemia or thrombocytopenia
- •Increased frequency of infections
- •No neutralizing anti-toxin or anti-mouse immunoglobulin G (IgG) antibodies to BL22 or PE38
- •No serum neutralization of > 75% of the activity of 1 μg/mL of BL22
- •No CNS disease requiring treatment
- •No hairy cell leukemia
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •More than 6 months
- •Hematopoietic
- •Absolute neutrophil count > 1,000/mm^3*
- •Platelet count > 40,000/mm^3 NOTE: *Patients with leukemia are eligible regardless of absolute neutrophil count; Grade III-IV pancytopenia or growth factor dependence allowed if due to disease
- •Bilirubin < 1.5 times upper limit of normal (ULN)
- •ALT and AST < 2.5 times ULN
- •Creatinine ≤ 1.5 mg/dL
- •FEV1 ≥ 60% of predicted
- •DLCO ≥ 55% of predicted
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV negative
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Prior bone marrow transplantation allowed
- •More than 3 weeks since prior biologic therapy, including interferon, denileukin diftitox, or LMB-2 immunotoxin
- •More than 3 months since prior monoclonal antibody therapy (e.g., rituximab)
- •Chemotherapy
- •See Disease Characteristics
- •More than 3 weeks since prior cytotoxic chemotherapy
- •Endocrine therapy
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排除标准
- 未提供