Y Zevalin and BEAM in Autologous Stem Cell Transplantation (ASCT) for Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The goal of this clinical research study is to see if high-dose chemotherapy (BEAM) and
      rituximab, given together with the new drug 90Y Zevalin, followed by a transplant of blood or
      marrow stem cells is safe. Another goal is to learn if this treatment can help decrease the
      chances of the cancer coming back.
    

Detailed description: 
      BEAM chemotherapy is the standard treatment for lymphoma. BEAM is a combination of
      chemotherapy drugs (carmustine, cytarabine, etoposide, and melphalan). Rituximab is an
      antibody made from human and mouse proteins. It reacts with a certain molecule on the surface
      of lymphoma cells and helps the body's immune system destroy the lymphoma cells. 90Y Zevalin
      is also an antibody made from mouse proteins. However, it has a particle of radiation
      attached to it. 90Y Zevalin works by attaching to lymphoma cells, and the radiation particle
      destroys the lymphoma cell.

      For this study, you will receive rituximab by vein followed by a dose of 111In Zevalin by
      vein (over 15 minutes). 111In Zevalin is different from the study drug (90Y Zevalin). 111In
      Zevalin has a different type of radioactive particle attached to it. This particle does not
      kill lymphoma cells, but it can be "seen" inside the body using a special camera (like an
      x-ray). 111In Zevalin is being used to predict how fast the study drug will travel in the
      body and how long the drug stays in the body. Doctors need to be able to see how much of the
      drug goes to the tumor and how much goes to normal organs to determine if it is safe to give
      90Y Zevalin on an outpatient basis. A scan will be done as soon as 111In Zevalin is given and
      about 2-24 hours later. Scans will also be done 2-3 days later. If the radiation in the 111In
      Zevalin is not a threat to normal organs and bone marrow, you may receive 90Y Zevalin. Seven
      (7) days after the 111In Zevalin injection, you will receive a second dose of rituximab
      followed by a dose of 90Y Zevalin by vein (over 15 minutes).

      Seven (7) days after the 90Y Zevalin injection, you will receive the BEAM combination of
      chemotherapy. You will receive carmustine (over 2 hours) on Day 1 of chemotherapy. You will
      receive cytarabine (over 2 hours) followed by etoposide (over 4 hours) twice a day on Days 2
      through 5. On Day 6, you will receive melphalan (over 20 minutes). A catheter (small flexible
      tube) will be placed in a large vein in your chest so that the chemotherapy drugs can be
      given to you more easily. This is called a central venous catheter. All of the chemotherapy
      drugs will be given through the central venous catheter.

      One day after finishing the chemotherapy, the stem cells that were collected earlier will be
      given back to you by vein over about 30 minutes. Starting on the same day, you will receive
      treatments with G-CSF by injection under the skin once a day. Treatment with G-CSF will
      continue until your blood counts reach a certain level.

      You will receive rituximab by vein (over 6 to 8 hours) on the day after the transplant and
      again 1-week later.

      Blood tests (about 1-2 tablespoons), urine tests, bone marrow collections, and x-rays will be
      done as needed to track the effects of the transplant. You will have transfusions of blood
      and platelets as needed. Blood tests (about 1 tablespoon) will be done once a day while you
      are in the hospital.

      Blood tests (about 1-2 tablespoons), urine tests, bone marrow collections, x-rays, CT scans,
      and PET scans will be done every 3 months for 1 year and then every 6 months for 5 years to
      check on the status of the disease.

      You will be asked to give some extra blood samples (around 1 tablespoon each) at study entry
      and upon return visits to M. D. Anderson. These samples will be used to test for certain
      molecules in the blood (HAMA and soluble CD20) and to check on the level of rituximab in the
      blood.

      Treatment will be given in the hospital at the University of Texas (UT) MD Anderson. You will
      need to stay in the hospital for about 3 to 4 weeks. You should stay in the Houston area for
      about 2 to 4 weeks after the transplant. After that, you will need to return to Houston from
      time to time for blood tests, urine tests, and other exams.

      This is an investigational study. This is an investigational study. 90Y-Zevalin is approved
      by the FDA for relapsed and refractory lymphoma. Its use in this trial, however, is
      investigational. All other drugs used in this study are FDA approved and are commercially
      available. Up to 60 participants will take part in this study. All will be enrolled at MD
      Anderson.
    

Intervention name(s): Y Zevalin; In Zevalin; Rituxan; BCNU; VP -16; Ara-C; Melphalan; Stem Cell Infusion; G-CSF
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Drug
Intervention description(s): Starting dose: 0.4 mCi/kg by vein after Rituxan infusion on Day -14.; Imaging dose: 5 mCi by vein following Rituxan infusion on Day -21.; 250 mg/m2 by vein on Day -21 and on Day -14.
1000 mg/m2 by vein on Days +1 and +8.; 300 mg/m2 by vein on Day -6.; 200 mg/m2 by vein every 12 hours on Days -5, -4, -3, and -2.; 200 mg/m2 by vein every 12 hours on Days -5, -4, -3,and -2.; 140 mg/m2 by vein on Day -1.; Autologous stem cell infusion on Day 0.; 5 mg/kg by vein daily starting Day 0 till recovery of granulocytes of 4.0 x 109/L.
Other intervention name(s): Rituximab; Carmustine; BiCNU; 1,3-bis(2-chloroethyl)-1-nitrosourea bis-chloronitrosourea; Cytarabine; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Alkeran; Filgrastim; Neupogen
Intervention MeSH terms: Cytarabine; Rituximab; Melphalan; Carmustine; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Lymphoma; Relapse B-cell CD20+ non-Hodgkin's lymphoma; High-dose BEAM chemotherapy; Y Zevalin; In Zevalin; Rituxan; Rituximab; BCNU; 1,3-bis(2-chloroethyl)-1-nitrosourea bis-chloronitrosourea; Carmustine; BiCNU; VP-16; Ara-C; Cytarabine; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Melphalan; Alkeran; G-CSF; Filgrastim; Neupogen; Stem cell infusion; Autologous stem cell transplantation