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

Study Overview
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Brief Summary
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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.

Detailed Description
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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. PROJECTED ACCRUAL: A total of 24 patients (12 per stratum) will be accrued for this study within 1-2 years.

Official Title
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Phase I Study of BL22, A Recombinant Immunotoxin for Chronic Lymphocytic Leukemia and CD22+ Lymphomas

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: BL22 immunotoxin
* Procedure: antibody-drug conjugate therapy
* Procedure: immunotoxin therapy


Participation Criteria
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Eligibility Criteria
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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: Age 18 and over Performance status ECOG 0-2 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 Hepatic Bilirubin < 1.5 times upper limit of normal (ULN) ALT and AST < 2.5 times ULN Renal Creatinine ≤ 1.5 mg/dL Pulmonary FEV1 ≥ 60% of predicted DLCO ≥ 55% of predicted 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 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 More than 1 week since prior steriods Less than 5 doses for non-treatment reasons (e.g., allergy prophylaxis) No evidence of disease response Radiotherapy More than 3 weeks since prior whole-body electron beam radiotherapy Radiotherapy within the past 3 weeks allowed provided the volume of bone marrow treated is < 10% AND the patient has measurable disease located outside the radiation port Surgery Not specified Other More than 3 weeks since prior retinoids More than 3 weeks since other prior systemic therapy for this malignancy

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BL22 immunotoxin|nan|
|Procedure: antibody-drug conjugate 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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B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, recurrent adult diffuse small cleaved cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, Waldenstrom macroglobulinemia, prolymphocytic leukemia