Anti-Tac(90 Y-HAT) to Treat Hodgkin's Disease, Non-Hodgkin's Lymphoma and Lymphoid Leukemia
Condition: Hodgkin's Disease; Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study will examine the use of a radioactive monoclonal antibody called yttrium
      90-labeled humanized anti-Tac (90 Y-HAT) for treating certain cancers. Monoclonal antibodies
      are genetically engineered proteins made in large quantities and directed against a specific
      target in the body. The anti-Tac antibody in this study is targeted to tumor cells and is
      tagged (labeled) with a radioactive substance called Yttrium-90 (Y-90). The study will
      determine the maximum tolerated dose of 90Y-HAT and examine its safety and effectiveness.

      Patients 18 years of age and older with Hodgkin's disease, non-Hodgkin's lymphoma and
      lymphoid leukemia who have proteins on their cancer cells that react with anti-Tac may be
      eligible for this study. Candidates are screened with a medical history and physical
      examination, blood and urine tests, electrocardiogram (EKG), chest x-ray, computed tomography
      (CT) scan or ultrasound of the abdomen, positron emission tomography (PET) scan of the neck
      and body, and skin test for immune reactivity to antigens (similar to skin tuberculin test).

      Before beginning treatment, participants may undergo additional procedures, including the
      following:

        -  Patients with suspicious skin lesions have a skin biopsy. An area of skin is numbed and
           a circular piece of skin about 1/4-inch diameter is removed with a cookie cutter-like
           instrument.

        -  Patients with hearing loss have a hearing test.

        -  Patients with neurological symptoms have a lumbar puncture (spinal tap). A local
           anesthetic is given and a needle is inserted in the space between the bones in the lower
           back where the cerebrospinal fluid circulates below the spinal cord. A small amount of
           fluid is collected through the needle.

        -  Patients who have not had a bone marrow biopsy within 6 months of screening also undergo
           this procedure. The skin and bone at the back of the hip are numbed with a local
           anesthetic and a small piece of bone is withdrawn through a needle.

      Patients receive 90 Y-HAT in escalating doses to determine the highest dose that can be
      safely given. The first group of three patients receives a low dose and, if there are no
      significant side effects at that dose, the next three patients receive a higher dose. This
      continues with subsequent groups until the maximum study dose is reached. 90 Y-HAT is given
      through a vein (intravenous (IV)) over a 2-hour period. In addition, a drug called Pentetate
      Calcium Trisodium Inj (Ca-DTPA) is given via IV over 5 hours for 3 days to help reduce the
      side effects of the 90Y-HAT. In some patients, the 90 Y-HAT may also be attached to a
      radioactive metal called Indium-111 to monitor what happens to the injected material. During
      infusion of the drug, patients undergo PET scanning to trace the path of the injected
      material in the body. For this procedure, the patient lies in the scanner, remaining in one
      position during the entire infusion.

      Blood and urine specimens are collected periodically over a 6-week period following the
      infusion to determine the level of the radioactive antibody. Bone marrow, lymph node, or skin
      biopsies may be done to determine how much of the antibody entered these sites. Patients
      whose disease remains stable or improves with therapy may receive up to six more infusions of
      90 Y-HAT, with at least a 6-week interval between treatments.
    

Detailed description: 
      Background:

      Cluster of differentiation 25 (CD25) is expressed on the malignant cells of patients with
      certain lymphoid malignancies as well as the non-malignant T cells that surround the
      malignant tumor cells of patients with Hodgkin's disease.

      Zenapax is a humanized monoclonal antibody that binds to CD25.

      Zenapax has been chemically modified by the addition of a chelating molecule to permit
      binding of radioactive yttrium.

      The yttrium labeled Zenapax binds to CD25 to deliver radiation treatment to the tumor.

      Objective:

      To assess the toxicity and therapeutic efficacy of (90)Yttrium-labeled humanized
      anti-Tac((90)Y-HAT) in patients with Tac-expressing hematologic malignancies.

      To determine the sites of localization of radiolabeled Zenapax.

      Eligibility:

      Patients with Hodgkin's disease and other CD25 positive lymphoid malignancies.

      The patient must have a granulocyte of at least 1,200/mm^3 and a platelet count of greater
      than 100,000/mm^3.

      Design:

      Patients will be treated with 10 mCi (if a bone marrow transplant was part of the patient's
      previous therapy) or 15 mCi of yttrium labeled Zenapax.

      Indium labeled Zenapax is given to demonstrate the antibody distribution and confirm
      localization at sites of tumor.

      Treatment is given every six weeks if tolerated and patients will be hospitalized for about
      one week for each treatment.

      Tumor response will be evaluated after every treatment. Stable or responding patients will
      continue treatment with evaluations after every cycle of treatment. Patients will be treated
      for up to seven cycles.
    

Intervention name(s): Y-90 Humanized Anti-Tac; Calcium-DTPA
Intervention type(s): Biological; Drug
Intervention description(s): 10 mCi (if a bone marrow transplant was part of the patient's previous therapy) or 15 mCi of yttrium labeled anti-TAC; followed by calcium trisodium Inj (Ca DTPA).; Ca-DTPA will be administered intravenously on Days 1-3 to clear the radioactive agent from the body
Intervention MeSH terms: Edetic Acid; Calcium; Pentetic Acid
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Yttrium 90; Radiolabeled; Anti -Tac; Calcium DTPA