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.
Full Title of Study: “PHASE I STUDY OF T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA USING THE MIK-BETA 1 MONOCLONAL ANTIBODY DIRECTED TOWARD THE IL-2R BETA SUBUNIT”
- Study Type: Interventional
- Study Design
- Primary Purpose: Treatment
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.
- Biological: monoclonal antibody Mik-beta-1
Participating in This Clinical Trial
- 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
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- National Cancer Institute (NCI)
- Overall Official(s)
- Thomas A. Waldmann, MD, Study Chair, NCI – Metabolism Branch;MET
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