BL22 Immunotoxin in Treating Patients With Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: The BL22 immunotoxin can locate tumor cells and kill them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of the BL22 immunotoxin in treating patients who have non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Determine the toxicity and therapeutic efficacy of recombinant BL22 immunotoxin in patients with CD22-positive B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia. Determine the pharmacokinetics, including the terminal elimination serum half-life area under the curve and volume of distribution, of recombinant BL22 immunotoxin in these patients. Determine the immunogenicity of recombinant BL22 immunotoxin in these patients. Determine the effect of recombinant BL22 immunotoxin on various components of the circulating cellular immune system in these patients. OUTLINE: This is a dose-escalation study. Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Patients may be retreated at least every 20 days for up to 25 courses in the absence of disease progression and sufficient neutralizing antibodies. Cohorts of 3-6 patients 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 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.

Official Title
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Phase I Study of Recombinant BL22 Immunotoxin in Patients With CD22-Positive B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: BL22 immunotoxin
* Procedure: antibody therapy
* Procedure: biological response modifier therapy
* Procedure: immunotoxin therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed chronic lymphocytic leukemia or prolymphocytic leukemia: Failed prior standard chemotherapy and treatment is medically indicated as evidenced by 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 OR Confirmed CD22+ B-cell indolent non-Hodgkin's lymphoma Stages II-IV that have failed at least 1 prior standard therapy and treatment is medically indicated No patients whose serum neutralizes BL22 or PE38 in tissue culture, due to antitoxin or antimouse-IgG antibodies No central nervous system disease requiring treatment If the patient is non-leukemic, the absolute neutrophil count must be greater than 1,000/mm3 and the platelet count greater than 40,000/mm3 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: More than 6 months Hematopoietic: See Disease Characteristics Hepatic: ALT and AST less than 5 times upper limit of normal Renal: Adequate renal function Pulmonary: Adequate pulmonary function Other: 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 At least 3 weeks since prior interferon for malignancy Chemotherapy: See Disease Characteristics At least 3 weeks since prior cytotoxic chemotherapy for malignancy Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy for malignancy Surgery: Not specified Other: At least 3 weeks since prior retinoids At least 3 weeks since prior systemic therapy for cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BL22 immunotoxin|nan|
|Procedure: antibody therapy|nan|
|Procedure: biological response modifier therapy|nan|
|Procedure: immunotoxin therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prolymphocytic leukemia, refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia, stage III grade I follicular small cleaved cell lymphoma, stage III grade II follicular mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV grade I follicular small cleaved cell lymphoma, stage IV grade II follicular mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, recurrent grade I follicular small cleaved cell lymphoma, recurrent grade II follicular mixed cell lymphoma, recurrent grade III follicular large cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult diffuse small noncleaved cell/Burkitt's lymphoma, contiguous stage II grade I follicular small cleaved cell lymphoma, contiguous stage II grade II follicular mixed cell lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade I follicular small cleaved cell lymphoma, noncontiguous stage II grade II follicular mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, stage III diffuse small lymphocytic/marginal zone lymphoma, contiguous stage II diffuse small lymphocytic/marginal zone lymphoma, noncontiguous stage II diffuse small lymphocytic/marginal zone lymphoma, stage IV diffuse small lymphocytic/marginal zone lymphoma, recurrent diffuse small lymphocytic/marginal zone lymphoma, recurrent mantle cell lymphoma