Anti-Tac(Fv)-PE38 (LMB-2) to Treat Cutaneous T-Cell Lymphomas
Condition: Lymphoma; T-Cell; Cutaneous
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
Intervention: LMB-2
Intervention description: 30 micrograms/kg every other day (QOD) x 3 every 4 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: LMB-2; Cutaneous T Cell Lymphoma; CTCL; Immunotoxin; Oncology

Summary:

      This study will evaluate the effectiveness of an experimental drug called LMB-2 for treating
      cutaneous T-cell lymphoma in patients who have a protein called cluster of differentiation 25
      (CD25) on their cancer cells. LMB-2 is a recombinant immunotoxin. It is made up of two parts:
      a genetically engineered monoclonal antibody that binds to CD25, and a toxin produced by
      bacteria that kills the cancer cells to which it binds. LMB-2 has killed CD25-containing
      cells in laboratory experiments and has caused tumors in mice to shrink. Preliminary studies
      in humans have shown some effectiveness in shrinking tumors in patients with various types of
      lymph and blood cancers.

      Patients 18 years of age and older with stage 1b to IV cutaneous T-cell lymphoma that has
      progressed within 2 years of systemic or topical therapy and who have CD25 receptor proteins
      on their cancer cells may be eligible for this study. Candidates are screened with a medical
      history and physical examination, blood and urine tests, electrocardiogram (EKG),
      echocardiogram, chest x-ray, computed tomography (CT) scans of the chest, abdomen and pelvis,
      skin punch biopsy to evaluate tumor infiltration in the skin, and a bone marrow biopsy on
      patients with stage IIa disease and higher. In addition, the patient's blood, bone marrow,
      tumor, or other tissue is tested to determine the presence of CD25 on cancer cells.

      Participants receive up to nine cycles of LMB-2 therapy as long as their cancer does not
      worsen and they do not develop serious side effects. Each 28-day cycle consists of 30-minute
      infusions of LMB-2 on cycle days 1, 3, and 5. The drug is infused through an intravenous (IV)
      catheter (plastic tube placed in a vein) or a central venous line - an IV tube placed in a
      large vein in the neck or chest that leads to the heart. In addition to drug therapy,
      patients undergo the following procedures:

      Blood draws: Blood is drawn before, during, and after each LMB-2 infusion to measure blood
      levels of the drug, evaluate its effects on the cancer cells, and monitor side effects. Blood
      tests are also done before and during each cycle to determine how the immune system is
      interacting with the drug.

      Disease evaluations: Patients undergo a careful skin examination, blood tests, chest x-ray,
      and EKG before each treatment cycle and at follow-up visits. A CT scan and echocardiogram
      (heart ultrasound) are done before the first cycle. Before the first and second cycles,
      patients have a biopsy of the lymphoma on the skin. If the biopsy is helpful in evaluating
      the disease response to LMB-2, additional biopsies may be requested prior to other cycles as
      well. A nuclear medicine scan may be done, and a bone marrow biopsy may be done in patients
      with stage II to IV disease. If these tests are helpful in understanding the response of the
      lymphoma to treatment, they may also be repeated prior to other cycles, with the patient's
      permission.

      Patients are admitted to the National Institutes of Health (NIH) Clinical Center for the
      first treatment cycle. Subsequent cycles are given as outpatients. If the infusions are well
      tolerated, patients may return home after about one week (or possibly longer if complications
      occur). After returning home, patients have blood tests done weekly by their local
      physicians.
    

Eligibility criteria:

        -  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.