Background: It is estimated that 40-50% of patients with cutaneous T-cell lymphoma (CTCL) have tumors that express cluster of differentiation 25 (CD25) (Tac or IL2Ra). Normal resting T-cells do not express CD25. LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of MAb anti-Tac and truncated Pseudomonas exotoxin. A phase I trial at National Cancer Institute (NCI) found that the maximum tolerated dose (MTD) of LMB-2 was 40 microg/Kg intravenous (IV) given every other day for 3 doses (QOD times 3) with prophylactic IV fluid. The most common adverse events were transient fever, hypoalbuminemia and transaminase elevations. In that trial, two of two patients with cutaneous T-cell lymphoma had clinical benefit (1 partial response (PR), 1 stable disease (SD)). In 1999 another recombinant fusion protein, denileukin diftitox, was approved by the Food and Drug Administration (FDA) for treatment of patients with advanced or recurrent CTCL expressing the high affinity interleukin-2 (IL-2) receptor. This receptor is composed of three subunits: CD25, CD122 and CD132. Because LMB-2 is cytotoxic to cells expressing CD25 without the other IL-2 receptor subunits needed to form the high affinity receptor, CD25+ CTCL patients are good candidates for further testing with LMB-2. Objectives: The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38 (LMB-2) in patients with Tac-expressing Cutaneous T-cell Lymphoma (CTCL). The primary endpoints of this trial are the response rate and response duration. We will also evaluate LMB-2 immunogenicity, pharmacokinetics, and toxicity, and monitor soluble Tac levels in the serum. These will be evaluated using routine hematologic and clinical evaluation, and when appropriate, by monitoring the phenotype of circulating T-cells or of biopsied tissues using antibodies to CD25. Eligibility: CD25+ CTCL based on immunohistochemistry or flow cytometry of blood. Patients must have measurable stage 1b-IV disease which progressed after greater than or equal 2 prior systemic or topical therapies. Labs required: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5-time upper limit, albumin greater than or equal 3, bilirubin less than or equal to 2.2, creatinine less than or equal to 2.0 (unless creatinine clearance greater than or equal to 50 ml/min), absolute neutrophil count (ANC) greater than or equal to 1000/ul, and platelets greater than or equal to 50,000/ul (ANC and platelets greater than or equal 500 and 10,000 if blood/marrow involvement). Design: Patients receive LMB-2 30 ug/Kg QOD time 3 every 4 weeks in absence of neutralizing antibodies or progressive disease. Dose escalation to 40 ug/Kg QOD times 3 if less than 2/6 dose limiting toxicity (DLT) at 30 ug/Kg times 3. 1st stage is 16 patients, to expand to 25 if greater than 1 of 16 patients respond.
* INCLUSION CRITERIA: Patients must have histopathological evidence of cluster of differentiation 25 (CD25) + cutaneous T-cell lymphoma (CTCL) confirmed by the National Institutes of Health (NIH) pathology department. One of the following must be present: Greater than or equal to 20 percent expression of CD25 on the lymphocytes in the skin at a site of a patch, plaque, or tumor. Greater than or equal to 20 percent of the peripheral blood Sezary cells must be CD25+. Measurable stage Ib-IV disease that has progressed after at least 2 prior systemic or topical therapies. Patients must have a Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and be at least 18 years old. Patients must be able to understand and give informed consent. Patients must be 4 weeks from any monoclonal antibodies. Patients must be greater than or equal to 3 weeks from any CTCL-specific therapy and have evidence of progressive disease. Patients who are on chronic steroids must be on a stable dose of Prednisone less than or equal to 20 mg/day (or equivalent dose of another steroid) for at least 3 weeks and have evidence of progressive disease. Female patients of childbearing potential must have a negative pregnancy test and must use effective contraception (a barrier form of contraception). The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must each be less than or equal to 2.5-times the upper limits of normal. Albumin must be greater than or equal to 3.0 gm/dL. Total bilirubin must be less than or equal to 2.2 mg/dL. The creatinine must be less than or equal to 2.0 mg/dL or the creatinine clearance must be greater than or equal to 50 ml/min. The absolute neutrophil count (ANC) must be greater than or equal to 1000/mm\^3 and the unsupported platelet count must be greater than or equal to 50,000/mm\^3 in patients without blood or bone marrow involvement. If there is blood or bone marrow involvement, the ANC must be greater than or equal to 500 mm\^3 and the platelets must be greater than or equal to 10,000/mm\^3. The cardiac ejection fraction as assessed by echocardiogram or nuclear medicine study must not be less than the institutional limit of normal. Pulmonary function studies must demonstrate a carbon monoxide diffusing capacity (DLCO) greater than or equal to 55 percent and a forced expiratory volume 1 (FEV1) greater than or equal to 60 percent of normal for inclusion. EXCLUSION CRITERIA: Patients whose serum neutralizes LMB-2 in tissue culture, due either to anti-toxin or anti-mouse-IgG antibodies. No patient whose serum neutralizes greater than 75 percent of the activity of 1 microg/mL of LMB-2 will be treated. Patients who are pregnant or breast-feeding. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients who are human immunodeficiency virus (HIV) positive, hepatitis B antigen positive, hepatitis C polymerase chain reaction (PCR) positive, or who have other chronic liver disease. Patients with symptomatic cardiac or pulmonary disease. Patients on warfarin therapy. Such patients may be eligible if they can be switched to heparin or low-molecular weight heparin therapy and are off warfarin at least 4 days prior to study enrollment. Active cancer requiring treatment.
está designado en este estudio
de ser asignado al grupo placebo