Immunotoxin Therapy in Treating Patients With Hairy Cell Leukemia

Study Overview
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Brief Summary
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RATIONALE: An immunotoxin can locate cancer cells and kill them without harming normal cells. This may be an effective treatment for hairy cell leukemia. PURPOSE: Phase I trial to study the effectiveness of BL22 immunotoxin in treating patients who have refractory or recurrent hairy cell leukemia.

Detailed Description
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OBJECTIVES: Assess the toxicity and therapeutic efficacy of recombinant BL22 immunotoxin in patients with refractory or recurrent CD22+ hairy cell leukemia. Define the pharmacokinetics of this drug, including the terminal elimination serum half-life area under the curve and volume of distribution, in these patients. Evaluate 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 dose-escalation study. Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats at least every 42 days for up to 4 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 at which no more than 1 of 6 patients experiences dose-limiting toxicity. PROJECTED ACCRUAL: A maximum of 46 patients will be accrued for this study within 3 years.

Official Title
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Phase I Study of BL22, a Recombinant Immunotoxin for Treatment of CD22+ Leukemias and Lymphomas

Conditions
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Leukemia

Intervention / Treatment
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* Biological: BL22 immunotoxin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed refractory or recurrent hairy cell leukemia Relapsed after less than 2 years of complete remission after purine analog therapy Must have at least one of the following indications for therapy: Progressive or massive splenomegaly Cytopenia defined by the following: Absolute neutrophil count less than 1,000/mm^3 OR Platelet count less than 100,000/mm^3 OR Hemoglobin less than 12 g/dL More than 20,000 hairy cells/mm^3 Symptomatic adenopathy Constitutional symptoms including tumor-related fever or bone pain Evidence of CD22 positivity by 1 of the following: More than 15% of malignant cells from a site must react with anti-CD22 by immunohistochemistry More than 30% of malignant cells from a site CD22+ by fluorescent-activated cell sorter More than 400 CD22 sites/cell (average) on malignant cells as assessed by radiolabeled anti-CD22 binding No CNS disease requiring treatment No patients whose serum neutralizes BL22 immunotoxin in tissue culture, due to either antitoxin or antimouse-IgG antibodies No patients whose serum neutralizes more than 75% of the activity of 1 microgram/mL of BL22 immunotoxin PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: More than 6 months Hematopoietic: See Disease Characteristics Pancytopenia due to disease allowed Hepatic: ALT and AST less than 2.5 times upper limit of normal (ULN) Bilirubin less than 1.5 times ULN Renal: Creatinine no greater than 2.0 mg/dL Pulmonary: FEV1 at least 60% of predicted DLCO at least 55% of predicted Other: HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Prior bone marrow transplantation allowed At least 3 weeks since prior interferon for the malignancy More than 3 months since prior monoclonal antibody therapy (e.g., rituximab) Chemotherapy: See Disease Characteristics At least 3 weeks since prior cytotoxic chemotherapy for the malignancy Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior whole body electron beam radiotherapy for the malignancy Radiotherapy within the past 3 weeks allowed provided less than 10% of total bone marrow was treated and patient has measurable disease outside the radiation port Surgery: Not specified Other: At least 3 weeks since prior retinoids for the malignancy At least 3 weeks since any other prior systemic therapy for the malignancy No concurrent therapeutic warfarin

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 |
| --- |
|Biological: BL22 immunotoxin|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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refractory hairy cell leukemia