LMB-2 to Treat Hairy Cell Leukemia
Condition: Hairy Cell Leukemia
MeSH terms: Leukemia; Leukemia, Hairy Cell
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Background: About 80% of patients with hairy cell leukemia (HCL) have malignant cells that
      express cluster of differentiation 25 (CD25) (Tac or Interleukin-2 receptor alpha (IL2Ra)).
      Normal resting B- and 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 x3). The
      most common adverse events were transient fever, hypoalbuminemia and transaminase elevations.
      In that trial, 4 of 4 patients with chemoresistant HCL had major responses, including one
      complete (CR) and 3 partial remissions. The patient with CR entered the trial transfusion
      dependent and now still has normal hemoglobin and platelet counts over 7 years later. Because
      HCL is more frequently cluster of differentiation 22 (CD22+) than CD25+ (100 vs 80%), HCL
      patients were subsequently treated with the anti-CD22 recombinant immunotoxin BL22 and no
      further HCL patients were treated with LMB-2. BL22 has induced 25 CRs out of 51 evaluable HCL
      patients. LMB-2 may be useful in patients incompletely responding to BL22, because it may
      distribute more evenly through extravascular sites of disease. Moreover, BL22 but not LMB-2
      has caused hemolytic uremic syndrome (HUS) in 7 patients, 6 with HCL, and several of these
      patients could benefit by LMB-2. Thus, LMB-2 may be a useful and potentially lifesaving agent
      in patients who are unable to receive or who have not responded adequately to BL22.

      Objectives: The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38
      (LMB-2) in patients with CD25-expressing hairy cell leukemia (HCL). The primary endpoint of
      this trial is response rate. We will also evaluate response duration, LMB-2 immunogenicity,
      pharmacokinetics, toxicity, and monitor soluble Tac levels in the serum.

      Eligibility: Patients must have CD25+ HCL cells by flow cytometry, cytopenia or high
      circulating HCL count, prior treatment with or inability to receive BL22, prior treatment
      with cladribine, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2, at
      least 18 years old, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) grade
      0-2, albumin grade 0-1, bilirubin less than or equal to 2.2, creatinine less than or equal to
      1.4 or creatinine clearance greater than or equal to 50, lack of high levels of neutralizing
      antibodies, lack of anti-CD25 Mab therapy for 12 weeks and other systemic treatment for 4
      weeks, no prior treatment with LMB-2, lack of other uncontrolled illness including 2nd
      malignancy, no human immunodeficiency virus (HIV) or hepatitis C positivity, no coumadin
      therapy, left ventricular ejection fraction (LVEF) greater than or equal to 45%, diffusing
      capacity of the lungs for carbon monoxide (DLCO) greater than or equal to 55%, and forced
      expiratory volume 1 (FEV1) greater than or equal to 60%.

      Design: Patients will receive LMB-2 at 40 microg/Kg every other day (QOD) x3 at intervals of
      at least 25 days for up to 6 cycles. Retreatment is permitted in the absence of neutralizing
      antibodies or progressive disease. Patients in CR may receive 2 consolidation cycles, or 4
      consolidation cycles if CR is with minimal residual disease.

      Dose level: LMB-2 40 microg/Kg QOD x3

      Expected Accrual: 5-10 patients/year, total of 25 patients
    

Intervention name(s): Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin
Intervention type(s): Drug
Intervention description(s): 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Biologic Therapy; Monoclonal Antibody; Immunotherapy; Pseudomonas Exotoxin; Targeted Therapy; Hairy Cell Leukemia; HCL