LMB-2 to Treat Hairy Cell Leukemia
Condition: Hairy Cell Leukemia
MeSH terms: Leukemia; Leukemia, Hairy Cell
Intervention: Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin
Intervention description: LMB-2 Infusion: 40 micro-g/Kg will be infused in 50 ml of 0.9% Sodium Chloride (NaCl) and 0.2% albumin via over 30 minutes every other day for 3 doses. Patients may receive up to six treatment cycles every 4 weeks.
Intervention MeSH terms: Immunotoxins
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
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Biologic Therapy; Monoclonal Antibody; Immunotherapy; Pseudomonas Exotoxin; Targeted Therapy; Hairy Cell Leukemia; HCL

Summary:

      Background:

        -  About 80% of patients with hairy cell leukemia (HCL) have tumor cells that have a
           protein on their surface called cluster of differentiation 25 (CD25).

        -  The experimental drug LMB-2 is a recombinant immunotoxin that has been shown to kill
           leukemia and lymphoma cells with the CD25 protein. (A recombinant immunotoxin is a
           genetically engineered drug that has two parts - a protein that binds or targets a
           cancer cell, and a toxin that kills the cancer cell to which it binds.)

      Objectives:

        -  To evaluate the safety and effectiveness of LMB-2 in patients with HCL whose cancer
           cells contain the CD25 protein.

        -  To evaluate the effects of LMB-2 on the immune system, determine how the drug is
           metabolized by the body and examine its side effects.

      Eligibility:

      -Adults with hairy cell leukemia whose tumor cells have CD25 on their surface

      Design:

        -  Up to 27 patients may be included in the study.

        -  Patients receive an infusion of LMB-2 through a vein every other day for three doses
           (days 1, 3, 5), constituting one treatment cycle.

        -  Patients may receive up to six treatment cycles every 4 weeks unless their cancer
           worsens or they develop unacceptable side effects.

        -  Blood is drawn weekly for various tests.

        -  Before each cycle and in follow-up visits, disease status is evaluated with a physical
           examination, blood tests, chest x-ray and electrocardiogram.

        -  Before the first cycle, patients may have a computed tomography (CT) scan,
           echocardiogram (heart ultrasound test) and bone marrow biopsy. With the patient's
           permission, these tests may be repeated before other cycles also.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Histopathological evidence of cluster of differentiation 25 (CD25)+ Hairy Cell
                  Leukemia (HCL) confirmed by the National Institutes of Health (NIH) pathology
                  department. This will require a monoclonal population of peripheral malignant
                  lymphocytes that are 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. HCLv (HCL variant) is usually CD25 negative, and eligibility would require
                  CD25+ HCLv.

               2. At least one of the following indications for treatment: neutropenia (absolute
                  neutrophil count (ANC) less than 1000 cells/ microL), anemia (hemoglobin (Hgb)
                  less than 10g/dL), thrombocytopenia (platelet (Plt) less than 100,000/ microL),
                  an absolute lymphocyte count of greater than 20,000 cells/microL or symptomatic
                  splenomegaly.

               3. Previous treatment with or inability to receive BL22 or HA22 recombinant
                  immunotoxin. Patients must have had at least 2 prior systemic therapies,
                  including 2 courses of a purine nucleoside analog (PNA), or 1 course of either
                  rituximab or BRAF inhibitor following a single prior course of PNA.

               4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.

               5. At least 18 years old.

               6. Understand and give informed consent.

               7. A negative pregnancy test in female patients of childbearing potential. Women
                  must not be breast-feeding.

               8. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or
                  equal to 5-times the upper limits of normal. Albumin greater than or equal to 3.0
                  gm/dL. Total bilirubin less than or equal to 2.2 mg/dL.

               9. Creatinine less than or equal to 1.4 mg/dL or creatinine clearance greater than
                  or equal to 50 ml/min.

              10. Serum that neutralizes less than or equal to 75% of the activity of 1 microg/mL
                  of LMB-2 using a bioassay.

              11. No systemic cytotoxic chemotherapy within 4 weeks of enrollment or systemic
                  steroids (except stable doses of Prednisone less than or equal to 20 mg/day, or
                  up to 4 doses of steroid given for non-therapy reasons) within 4 weeks of
                  enrollment.

              12. No anti-cluster of differentiation 25 (CD25) monoclonal antibody therapy within
                  12 weeks of enrollment.

              13. No prior treatment with LMB-2.

              14. Patients may not be receiving any other investigational agents.

              15. Patients should not have uncontrolled intercurrent illness including, but not
                  limited to, symptomatic congestive heart failure, unstable angina pectoris,
                  cardiac arrhythmia, or psychiatric illness/social situations that would limit
                  compliance with study requirements.

        EXCLUSION CRITERIA:

          -  Patients who have human immunodeficiency virus (HIV) or hepatitis C. Patients would
             not be excluded for hepatitis B surface antigen positivity if on Lamivudine.

          -  Patients receiving coumadin.

          -  Patients with a left ventricular ejection fraction of less than 45%.

          -  Patients with a diffusing capacity of the lungs for carbon monoxide (DLCO) less than
             55% of normal or an forced expiratory volume 1 (FEV1) less than 60% of normal based on
             either National Institutes of Health (NIH) or United States of America (USA) normal
             ranges.

          -  Patients who have an active 2nd malignancy requiring systemic treatment.