Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies 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 monoclonal antibody therapy in treating patients who have chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Evaluate the toxicity of murine monoclonal antibody Mik-beta-1 (MOAB Mik-beta-1) in patients with T-cell large granular lymphocytic leukemia associated with granulocytopenia, anemia, or thrombocytopenia. Determine the clinical response in patients treated with this drug. Assess the effect of this drug on the number of circulating CD3+, CD8+ expressing granular lymphocytes and the number of polymorphonuclear leukocytes, red blood cells, and platelets in this patient population. Monitor patients for the time course of decline in circulating infused MOAB Mik-beta-1 and for the production of human antibodies to IV infused murine MOAB Mik-beta-1. OUTLINE: This is a dose-escalation study. Patients receive monoclonal antibody Mik-beta-1 (MOAB Mik-beta-1) IV over 2 hours on days 1, 4, 7, and 10. Patients achieving a complete response (CR) or partial response (PR) may receive 1 additional course beginning no sooner than 4 weeks after completion of the first course, in the absence of antibodies to MOAB Mik-beta-1. Treatment continues in the absence of disease progression, unacceptable toxicity, or severe allergic reaction. Cohorts of 3-6 patients receive escalating doses of MOAB Mik-beta-1 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. Patients are followed at 6-10 days and at 4-6 weeks after therapy. Patients with a PR or CR may be followed every 6 months for 2 years or until relapse. All patients are followed for survival. PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.

Official Title
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PHASE I STUDY OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA USING THE MIK-BETA 1 MONOCLONAL ANTIBODY DIRECTED TOWARD THE IL-2R BETA SUBUNIT

Conditions
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Leukemia

Intervention / Treatment
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* Biological: monoclonal antibody Mik-beta-1


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed T-cell large granular lymphocytic (T-LGL) leukemia associated with clinically significant hematocytopenia demonstrated by one of the following values while off growth factor support: Absolute neutrophil count less than 1,000/mm^3 Hemoglobin less than 8 g/dL Platelet count less than 50,000/mm^3 Clinically evaluable disease with peripheral blood T-LGL leukemia cells expressing the CD3+, CD8+ phenotype detectable by FACS Monoclonal T-cell population in peripheral blood (circulating mononuclear cells) demonstrated by TCR beta or gamma chain gene rearrangement PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life expectancy: More than 2 months Hematopoietic: See Disease Characteristics No active major bleeding episode within the past 4 weeks Hepatic: Direct bilirubin less than 1.5 mg/dL Renal: Creatinine less than 2.0 mg/dL Other: No concurrent serious active infection Patients with fever without apparent site of infection may begin study while on antibiotics as long as the following are true: No pathogenic organism in culture Afebrile (maximum temperature less than 38°C) for at least 5 days HIV negative No other primary cancer other than basal cell skin cancer Not pregnant or nursing Negative pregnancy test PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior interferon Concurrent filgrastim (G-CSF), sargramostim (GM-CSF), interleukin-11, or similar sustained-release/long-acting product (e.g., pegylated G-CSF) allowed if dose established at least 4 weeks prior to study participation No concurrent interferon Chemotherapy: At least 4 weeks since prior chemotherapy No concurrent chemotherapy Endocrine therapy: Concurrent corticosteroids allowed if dose established at least 3 weeks prior to study participation Radiotherapy: Not specified Surgery: Not specified Other: At least 1 week since completion of prior antibiotic regimen for serious infectious episode No other concurrent investigational drugs

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: monoclonal antibody Mik-beta-1|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 chronic lymphocytic leukemia, T-cell large granular lymphocyte leukemia