Clinical Trial: Hu-Mik-beta1 to Treat T-Cell Large Granular Lymphocytic Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Open-Label Single-Dose Study of Humanized Mik-Beta-1 Monoclonal Antibody Directed Toward the IL-2R/IL-15R-Beta Subunit (CD122) in T Cell Large Granular Lymphocytic Leukem

Brief Summary:

This study will examine the use of the humanized Mik-beta-1 (Hu-Mik-beta1) antibody in patients with T-cell large granular lymphocytic leukemia (T-LGL). Patients with T-LGL often have reduced white blood cells, red blood cells, and platelets, and increased numbers of abnormal cells called large granular lymphocytes (LGLs). Patients may have recurrent infections, anemia, or abnormal bleeding. Hu-Mik-beta1 attaches to LGL cells and blocks the action of growth factors called interleukins that stimulate LGL growth. Blocking these interleukins may stop T-LGL leukemia cells from growing. This study will determine the dose and frequency of treatment with Hu-Mik-(SqrRoot) 1 that can safely be given to patients to coat the surface of their leukemic cells with antibody, determine how long the antibody lasts in the blood after injection, and examine the side effects and possible benefits of the drug in these patients.

Patients age 18 or older with T-LGL may be eligible for this study. Candidates will be screened with a medical history and physical examination, review of pathology studies, skin biopsy, evaluation of rheumatoid arthritis if present, chest x-ray, computerized tomography (CT) scans and other imaging studies as needed, bone marrow biopsy, and blood and urine tests.

Participants will receive a single dose of Hu-Mik-beta1 by a 90-minute infusion through a vein. Groups of patients will be treated with increasing doses (0.5, 1.0, and 1.5 mg/kg) of the antibody. Patients who develop serious drug side effects are taken off the study. The treatment requires a 3- to 4-day hospital stay. In addition to Hu-Mik-(SqrRoot) 1 treatment, patients will undergo the following tests and procedures:

  • Collection of blood for 8 days following the dose of Hu-Mik-be

    Detailed Summary:

    Background:

    • T cell large granular lymphocyte (T-LGL) leukemia is a chronic lymphoproliferative disorder associated with granulocytopenia, anemia and/or thrombocytopenia.
    • Although agents such as cyclosporine and methotrexate have shown activity in T-LGL, treatment of T-LGL has remained largely undefined and symptomatic.
    • The shared IL-2R/Il-15R Beta receptor (CD122) is over expressed on T-LGL cells and may stimulate growth T-LGL cells through its interaction with IL-15.
    • Hu-Mik-Beta1 is a humanized monoclonal antibody that binds to IL-2R/IL-15R Beta
    • Hu-Mik-Beta1 may inhibit the growth and exert cytotoxic activity against T-LGL cells.

    Objectives:

    • To determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of Hu-Mik-Beta1 when administered to patients with T-LGL.
    • To determine the dose of Hu-Mik-Beta1 required to saturate IL-2R/IL-15R Beta (CD122) on -T-LGL cells in the peripheral blood.
    • To determine the pharmacokinetics and serum die-away curve of Hu-Mik-Beta1.
    • To provide preliminary information on the clinical response following single dose administration of Hu-MiK-Beta1 in patients with CD122 expressing T-LGL leukemia.

    Eligibility:

    --T cell large granular lymphocyte leukemia (T-LGL).

    Patients must have a granulocyte count of less than 1000/microL, or hemoglobin less than 10 gm/dL, or be tra
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome: DLT and MTD of Hu MIK Beta 1 [ Time Frame: 21 days ]

    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: January 14, 2004
    Date Started: January 6, 2004
    Date Completion:
    Last Updated: May 12, 2017
    Last Verified: March 2, 2017