Zevalin/BEAM/Rituximab vs BEAM/Rituximab With or Without Rituximab in Autologous Stem Cell Transplantation
Condition: Diffuse Large Cell Lymphoma; Lymphoma
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Study type: Interventional
Phase: Phase 2

Summary: 
      The goal of this clinical research study is to learn if the addition of 90Y Zevalin to BEAM
      chemotherapy (carmustine, etoposide, cytarabine, and melphalan) and rituximab is more
      effective than the combination of BEAM and rituximab alone in patients with lymphoma who
      receive a stem cell transplant.
    

Detailed description: 
      The Study Drugs:

      90Y Zevalin is designed to attach to lymphoma cells, and destroy the cells using a radiation
      particle that is attached to it.

      111In Zevalin is like 90Y Zevalin, but the radioactive particle that is attached to it does
      not kill lymphoma cells. The radioactive particle makes the drug able to be seen inside your
      body. It is being used in this study to predict how fast the study drug will travel in the
      body and how long the drug stays in the body.

      Carmustine, etoposide, cytarabine, and melphalan (BEAM) are designed to kill lymphoma cells
      by damaging the cells DNA.

      Rituximab is designed to attach to lymphoma cells, which may cause them to die.

      Study Groups 1 and 2:

      If you are found to be eligible to take part in this study, you will be randomly assigned (as
      in the toss of a coin) to 1 of 2 groups. You will have an equal chance of being assigned to
      each group. Group 1 will receive 90Y Zevalin along with rituximab and BEAM therapy. Group 2
      will receive rituximab and BEAM therapy. You and the study staff will know which group you
      are in.

      Study Drug Administration:

      If you are in Group 1, you will receive rituximab through a needle in your vein (over 4-5
      hours) followed by 111In Zevalin by vein (over 15 minutes). A nuclear scan will be done
      within the following 40 to 48 hours to see how the drug is traveling through your body.

      If intolerable side effects are not shown by the scans, you will receive rituximab (over 4-5
      hours) and 90Y Zevalin (over 15 minutes) through a needle in your vein 7 days after the 111In
      Zevalin infusion.

      You will begin BEAM chemotherapy 7 days after the second 90Y Zevalin infusion.

      BEAM Chemotherapy:

      Both groups will have 7 days of BEAM combination chemotherapy.

        -  On Day 1, you will receive carmustine through a needle in your vein over 1 hour.

        -  On Days 2-5 you will receive cytarabine by vein (over 1 hour) followed by etoposide
           (over 3 hours). Both infusions will be repeated every 12 hours on Days 2-5.

        -  On Day 6 you will be given melphalan by vein over 30 minutes.

        -  On Day 7 the stem cells that were collected earlier from you will be given back
           ("transplanted") through a catheter over 30-45 minutes.

        -  You will also receive rituximab by vein (over 5-7 hours) on Day 8.

      You will receive rituximab (over 4-5 hours) 7 days after the stem cell transplant. You will
      receive G-CSF by injection once a day starting 7 days after the stem cell transplant until
      your blood counts return to a normal level. You should stay in the Houston area for about 2-4
      weeks after the transplant.

      Study Procedures:

      At about 1 month after the transplant you will have x-rays, CT scans, and positron emission
      tomography (PET) scans. You will also have a bone marrow aspirate and biopsy to check the
      status of the disease.

      Blood (about 1 tablespoon) will be drawn once a day while you are in the hospital to check
      your blood counts.

      Blood tests (about 1-2 tablespoons), urine tests, bone marrow collections, and x-rays may be
      done as needed to track the effects of the transplant.

      You will have transfusions of blood and platelets as needed.

      Study Groups A and B:

      About 1 month after the transplant, you will be randomly assigned (as in the toss of a coin)
      to 1 of 2 new groups (Group A and Group B). Group A will receive rituximab by vein over 5-7
      hours, once every 3 months, starting 3 months after the stem cell transplant. You will
      receive rituximab for the first 18 months after the stem cell transplant. Group B will not
      receive rituximab. You will have an equal chance of being in each group.

      Follow-up Visits:

      You will return to the clinic every 6 months for 5 years to check the status of the disease.
      The following tests and procedures will be performed:

        -  Blood (about 1-2 tablespoons) and urine will be collected for routine tests.

        -  You will have a bone marrow biopsy to check the status of the disease.

        -  You will have a chest x-ray and a CT scan.

        -  You will have a PET scan.

      Length of Study:

      You may stay on study as long as you are benefitting. You will be taken off-study if the
      disease gets worse or intolerable side effects occur.

      This is an investigational study. 90Y-Zevalin is approved by the FDA for relapsed and
      refractory lymphoma. Its use in this study is investigational. 111In Zevalin, Carmustine,
      etoposide, cytarabine, melphalan, and Rituximab are all FDA approved and commercially
      available. However, their use together in this study is also investigational. Up to 50
      patients will be take part in this study. All will be enrolled at MD Anderson.
    

Intervention name(s): Zevalin; Carmustine; Etoposide; Cytarabine; Melphalan; Rituximab; Stem Cell Transplant
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Procedure
Intervention description(s): (111In Zevalin) 5 millicurie (mCi) by vein and (90Y Zevalin) 0.4 mCI/kg by vein.; 300 mg/m^2 by vein.; 200 mg/m^2 by vein every 12 hours.; 200 mg/m^2 by vein every 12 hours.; 140 mg/m^2 by vein.; Arm 1, Arm 2 = 250 mg/m^2 by vein;
Arm 1, Arm 2, Arm 3, Arm 4 = 1000 mg/m^2 by vein following Stem Cell Transplant;
Arm 1, Arm 3 = 375 mg/m² by vein Maintenance Therapy.; Injection of stem cells (Autologous SCT)
Other intervention name(s): Ibritumomab; IDEC-Y2B8; BCNU; BiCNU; VePesid; Ara-C; Cytosar; DepoCyt; Cytosine arabinosine hydrocholoride; Rituxan; Stem Cell Transplantation; SCT
Intervention MeSH terms: Cytarabine; Rituximab; Etoposide; Melphalan; Carmustine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diffuse Large Cell Lymphoma; Lymphoma; Zevalin; Ibritumomab; IDEC-Y2B8; Carmustine; BCNU; BiCNU; Etoposide; VePesid; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Melphalan; Rituximab; Rituxan; BEAM