Campath-1H for Treating Adult T-Cell Leukemia/Lymphoma
Condition: Acute T-Cell Leukemia-Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Intervention: Alemtuzumab
Intervention description: Infusion of Campath-1H 3 mg on day # 1, 10 mg on day #2, and 30 mg day # 3 followed by maintenance Campath-1H 30 mg intravenously three times per week. Patients are eligible to receive a maximum of 12 weeks of maintenance Campath-1H treatment.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Monoclonal Antibody; HTLV-1; CD52; Flow Cytometry; Antibody Saturation; Adult T-Cell Leukemia (ATL); ATL

Summary:

      This study will examine the safety and effectiveness of Alemtuzumab (Campath-1H) for treating
      patients with adult T-cell leukemia/lymphoma (ATL). ATL is caused by a virus called human
      T-cell lymphotrophic virus type-1 (HTLV-1) that infects lymphocytes (white blood cells)
      called T-cells. Cancerous cells can be found not only in the blood, but also in the skin,
      lungs, lymph nodes, liver, bone, bone marrow, spleen, and meninges (tissues covering the
      brain). There are four categories of ATL, based on the aggressiveness of disease-smoldering,
      chronic, lymphoma, and acute. Campath-1H is a monoclonal antibody that attaches to and kills
      normal and cancerous lymphocytes, including T cells. Although Campath-1H is an experimental
      drug for treating ATL, it is approved by the Food and Drug Administration for treating
      chronic lymphocytic leukemia.

      Patients 18 years of age and older with any type of ATL except smoldering may be eligible for
      this study. Candidates are screened with a medical history and physical examination, photos
      of skin lesions, measurement of lesions such as lymph nodes and skin nodules, blood and urine
      tests, electrocardiogram (EKG), chest x-ray, computed tomography (CT) scan or ultrasound of
      the abdomen, skin biopsy, bone marrow aspirate and biopsy, skin test, and lumbar puncture
      (spinal tap). Participants undergo treatment in two phases, as follows:

        -  Dose escalation phase: Patients receive an infusion of Campath-1H daily for three days.
           The initial dose is low and is increased daily as long as there are no side effects, or
           only mild reactions, until the patient is receiving the maximum dose of 30 milligrams
           per day.

        -  Stable dose phase: Patients receive infusions of Campath-1H 30 mg three times a week for
           up to 12 weeks.

      In addition to treatment, patients are evaluated with the following tests and procedures:

        -  History and physical examination every 4 weeks.

        -  Blood tests every 4 weeks.

        -  CT scans to measure the size of the tumors every 4 weeks.

        -  Skin biopsies (if skin disease is present) and lymph note aspirates: Up to five biopsies
           and five aspirates may be taken to help diagnose the disease and evaluate the effect of
           Campath-1H on the cancer.

        -  Bone marrow biopsy: This procedure may be done to document or monitor disease progress.

      Patients receive treatment for up to 12 weeks. Treatment may stop earlier if the patient
      achieves a complete response before the end of 12 weeks. Patients completing the study are
      followed periodically with a history and physical examination, blood and urine tests, tumor
      evaluation, skin biopsy and skin testing. They are seen monthly at first and then at 3-month
      intervals the first year; every 4 months the second year, every 6 months for the third
      through fifth years, and then yearly.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have serum antibodies directed to Human T-lymphotropic Virus Type 1
             (HTLV-1).

          -  All patients must have a histologically confirmed diagnosis of adult T- cell
             leukemia/lymphoma and more than 10% of the malignant cells must express CD52 and CD25.

          -  All stages of Tac-expressing adult T-cell leukemia except smoldering are eligible:
             patients with chronic, lymphoma or acute Acute T-cell leukemia/lymphoma (ATL) are
             eligible.

          -  Patients must have measurable disease. All patients with greater than 10% abnormal
             (i.e. Tac homogeneous strongly expressing) peripheral blood mononuclear cell (PBMC)in
             the peripheral blood will be deemed to have measurable disease.

          -  The patient must have a granulocyte count of at least 100/mm(3) and a platelet count
             of greater than or equal to 50,000/mm(3).

          -  Patients must have a creatinine of less than 3.0 mg/dl.

          -  Omission of cytotoxic chemotherapy for ATL for 3 weeks prior to entry into the trial
             is required. However patients receiving a stable dose of corticosteroids for at least
             three to four weeks without evidence of tumor response will be eligible.

          -  Patients must have a life expectancy of greater than 2 months.

          -  Eligible patients must be greater than or equal to 18 years old. There is no upper age
             limit.

          -  Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic
             pyruvic transaminase (SGPT) value less than or equal to 2.5-fold greater than the
             upper limit of normal and bilirubin less than or equal to 3.0/dl. If a liver function
             test is judged to be elevated due to the underlying ATL, this parameter will be
             considered an unevaluable parameter for toxicity determinations.

          -  Patients must be able to understand and sign an Informed Consent form.

          -  All patients must use adequate contraception during participation in this trial and
             for three months after completing therapy.

        Exclusion Criteria:

          -  Patients with symptomatic leukemic meningitis will be excluded. However patients that
             have both ATL and another HTLV-1-associated disease, tropical spastic paraparesis
             (TSP) will be included.

          -  Pregnant and nursing patients are not eligible for the study. Because the effects of
             CAMPATH-1H on the developing fetus are unknown pregnant women will be excluded.
             Breast-feeding in patients with HTLV-1 infection is contraindicated because of the
             risk of transmission of the virus to the child. In addition, CAMPATH-1H may be present
             in breast milk and produce adverse events in the breast-feeding child.

          -  Human immunodeficiency virus (HIV) positive patients are excluded from the study.
             CAMPATH-1H may produce a different pattern of toxicities in patients with HIV
             infection and in addition the depletion of T cells produced by CAMPATH-1H may have
             adverse effects on HIV positive individuals.

          -  Patients with smoldering ATL are excluded.

          -  Patients with previously received Campath-1GH are ineligible.