Anti-Tac(Fv)-PE38 (LMB-2) to Treat Chronic Lymphocytic Leukemia
Condition: Leukemia; Lymphocytic; Chronic
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: LMB-2
Intervention description: 40 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: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: LMB-2; Chronic Lymphocytic Leukemia; CLL; Immunotoxin; Oncology; Lymphocytes; Hematological Disease; Monoclonal Antibody; Neutralizing Antibodies

Summary:

      This study will evaluate the effectiveness of an experimental drug called LMB-2 for treating
      chronic lymphocytic leukemia (CLL) 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 cancer cells
      with CD25 on their surface, and a toxin produced by bacteria that kills the cancer cells to
      which it binds. LMB-2 has killed CD 25-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 CLL who have CD25 receptor proteins on their cancer
      cells and whose disease has progressed within 2 years of treatment with fludarabine 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, and a bone marrow biopsy.

      Participants receive up to six cycles of LMB-2 therapy. 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. Patients are admitted to
      the National Institutes of Health (NIH) Clinical Center for the first treatment cycle. If the
      infusion is well tolerated, subsequent cycles may be given on an outpatient basis. 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 physical examination, blood tests, chest x-ray,
           and EKG before each treatment cycle and at follow-up visits. With the patient's
           permission, CT scans, echocardiogram, and bone marrow biopsies may be repeated before
           some treatment cycles if these tests prove useful in evaluating the disease response to
           LMB-2.

      Patients may receive up to six cycles of LMB-2 as long as their cancer does not worsen and
      they do not develop serious side effects. At the end of the treatment cycles, patients will
      have blood tests done weekly by their local physician, and the results will be sent to the
      NCI study investigators.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients must have histopathological evidence of CD25+ CLL or prolymphocytic leukemia (PLL)
        confirmed by the NIH pathology department. This requires that at least 50% of the
        peripheral malignant lymphocytes be CD25 positive by fluorescence activated cell sorting
        (FACS) with anti-CD25 antibody. Positive expression in a FACS assay is defined as more than
        2 times the mean fluorescence intensity (MFI) of the control antibody by FACS, or greater
        than 400 CD25 sites/cell by FACS or radiolabeled binding assay.

        In the three stage modified Rai system, patients must be intermediate or high risk. This
        means they must have circulating CLL cells and at least one of the following:
        lymphadenopathy, splenomegaly, hepatomegaly, anemia (Hgb less than 11g/dL), or
        thrombocytopenia (Plt less than 100,000/ul).

        Patients must have had progressive disease after prior standard therapy containing either a
        purine analog or an alkylating agent.

        Patients must not have received systemic cytotoxic chemotherapy within 4 weeks of
        enrollment or systemic steroids (except stable doses of Prednisone less than or equal to 20
        mg/day) within 4 weeks of enrollment.

        Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.

        At least 18 years old.

        Patients must be able to understand and give informed consent.

        Female patients of childbearing potential must have a negative pregnancy test and all
        patients 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 except
        in patients with Gilbert's syndrome (as defined by greater than 80% unconjugated bilirubin)
        it must be less than 5 mg/dl.

        The creatinine must be less than or equal to 1.4 mg/dL or the creatinine clearance must be
        greater than or equal to 50 ml/min as measured from a 24-hour urine collection.

        Patients should not have 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.

        EXCLUSION CRITERIA:

        Patients whose serum neutralizes LMB-2 in tissue culture, due either to anti-toxin or
        anti-mouse-lgG antibodies. No patient whose serum neutralizes greater than 75% of the
        activity of 1 micro g/mL of LMB-2 will be treated.

        Patients who received LMB-2 on another trial.

        Monoclonal antibody therapy within 12 weeks of enrollment.

        Patients who are pregnant or breast-feeding.

        Patients who are human immunodeficiency virus (HIV) positive.

        Patients who have hepatitis C or chronic liver disease. Patients would not be excluded for
        hepatitis B surface antigen positivity if on Lamivudine.

        Patients receiving warfarin for anticoagulation.

        Patients with a left ventricular ejection fraction of less than the institutional lower
        limit of normal.

        Patients with a carbon monoxide diffusing capacity (DLCO) less than 55% of normal or an
        forced expiratory volume 1 (FEV1) less than 60% of normal.

        Patients who have active cancer requiring treatment.