Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT)
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia
Study type: Interventional
Phase: Phase 2

Summary: 
      The goal of this clinical research study is to learn if adding Zevalin (ibritumomab tiuxetan)
      to low-intensity chemotherapy (the combination of rituximab, bendamustine, and fludarabine),
      followed by an allogeneic stem cell transplant, can help to control lymphoma. The safety of
      this combination will also be studied.

      Two (2) forms of ibritumomab tiuxetan will be used in this study. 90Y-ibritumomab tiuxetan is
      designed to attach to lymphoma cells and destroy the cells using a radioactive particle that
      is attached to it. 111In-ibritumomab tiuxetan is like 90Y- ibritumomab tiuxetan, 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.

      Rituximab is designed to attach to lymphoma cells, which may cause them to die.

      Bendamustine is designed to damage and destroy the DNA (genetic material) of cancer cells.

      Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may
      increase the likelihood of the cells dying.
    

Detailed description: 
      Study Drug Administration and Procedures:

      The chemotherapy, some of the other drugs in this study, and the stem cell transplant will be
      given by vein through your central venous catheter (CVC). A central venous catheter is a
      sterile flexible tube that will be placed into a large vein while you are under local
      anesthesia and will remain in your body during treatment. Your doctor will explain this
      procedure to you in more detail, and you will be required to sign a separate consent form.
      Blood samples will also be drawn through the CVC.

      On Days -22 (22 days before you receive the stem cell transplant), you will receive rituximab
      by vein over 3-4 hours. You will then receive 111In-ibritumomab tiuxetan by vein over 30
      minutes.

      From Day -22 through Day -16, you will have scans called whole-body planar scintigraphy
      imaging. In these scans, a special camera will capture 2-dimensional images of the whole body
      to see where the radioactive 111In- ibritumomab tiuxetan that was injected on Day -22 has
      spread. No additional radiation will be used in this scan. Scintigraphy will be performed
      right after the injection, then 3-6 hours after the injection, then 24, 72, and 144 hours
      (+/- 2 hours) after the injection.

      After the last scintigraphy imaging scan, the scans will be reviewed to learn how much
      radiation has traveled to different organs and to decide how much 90Y- ibritumomab should be
      used.

      On Day-14, you will receive rituximab by vein over 3-4 hours. You will then receive the
      calculated dose of 90Y-ibritumomab tiuxetan by vein over 30 minutes.

      On Days -5, -4, and -3, you will receive fludarabine and bendamustine by vein over 1 hour
      each day.

      On Days -3 through Day 100, if your stem cells are from cord blood, you will receive
      mycophenolate mofetil (MMF) by vein or by mouth. MMF is designed to block the donor cells
      from growing and spreading in a way that could cause graft versus host disease (GVHD -- a
      condition in which transplanted tissue attacks the recipient's body).

      Starting on Day -2, if your stem cells are from a related or matched unrelated donor, you
      will receive tacrolimus by vein as a continuous (nonstop) infusion until you are able to take
      it by mouth to help prevent GVHD. You will then take tacrolimus by mouth 2 times a day for
      about 3 months. After that, your tacrolimus dose may be lowered if you do not have GVHD. Your
      doctor will discuss this with you.

      On Days -2 and -1, if your stems cells are from a matched unrelated donor or from cord blood,
      you will receive thymoglobulin (ATG) by vein over about 4 hours. ATG is designed to weaken
      your immune system to reduce the risk of rejecting of the transplant.

      On Day 0, you will receive the blood stem cells by vein over about 30-45 minutes. Blood (less
      than 1 teaspoon) will also be drawn to measure how much (if any) radiation from the 90Y-
      ibritumomab tiuxetan is left in the blood.

      Starting on Day 0, if your stem cells are from cord blood, you will receive filgrastim
      (G-CSF) through a needle under the skin 1 time a day every day until your white blood count
      begins to recover. G-CSF is designed to help cells in the bone marrow to divide, which helps
      raise white blood cells counts more quickly, lower fever, and decrease the risk of infection.

      On Days 1, 3, and 6, if your stem cells are from a related or matched unrelated donor, you
      will receive methotrexate over 30 minutes each day by vein to help prevent GVHD. Patients
      receiving a matched unrelated donor will also be given methotrexate on Day 11 after the
      transplant.

      Starting on Day 7, if your stem cells are from a related or matched unrelated donor, you will
      receive G-CSF through a needle under the skin 1 time a day every day until your white blood
      count begins to recover.

      When your doctor thinks they are needed, you will also receive antibiotics and antifungal
      drugs to help prevent and/or treat infections. Your doctor will tell you more about how these
      drugs are given and possible side effects.

      You will be in the hospital for about 3-4 weeks after you receive the stem cell transplant.
      During this time, the following tests and procedures will be performed at any point that your
      doctor thinks they are needed:

        -  You will have a physical exam, including measurement of your vital signs (blood
           pressure, heart rate, temperature, and breathing rate).

        -  You will be asked about how you are feeling and about any side effects you may be
           having.

        -  Blood (about 4-6 teaspoons) will be collected for routine tests, to check your kidney
           and liver function, and to learn if and how well the transplant is working.

      The following may also be performed if at any point the doctor thinks they are needed:

        -  You may have imaging scans to check the status of the disease and/or to check for
           possible infections.

        -  You may have a bone marrow biopsy to check the status of the disease. To collect a bone
           marrow biopsy, an area of the hip or other site is numbed with anesthetic, and a small
           amount of bone marrow and bone is withdrawn through a needle.

        -  You may have transfusions of blood and/or platelets.

      You must stay in the Houston area for about 100 days after the stem cell transplant.

      Long-Term Follow-Up:

      About 3, 6, and 12 months after the stem cell transplant:

        -  Blood (about 6 teaspoons) will be collected for routine tests, to check kidney and liver
           function, and to see how well the transplant has taken.

        -  You will have CT and PET scans to check the status of the disease.

        -  You will have a bone marrow biopsy/aspirate to check the status of the disease.

      About 2 and 3 years after the stem cell transplant, you will receive a phone call that will
      take less than 10 minutes to learn how you are doing.

      Length of Study:

      You will be on study for up to about 3 years. You may be taken off study early if the disease
      gets worse, if you have any intolerable side effects, of if you are unable to follow study
      directions.

      You should talk to the study doctor if you want to leave the study early. If you are taken
      off study early, you still may need to return for routine post-transplant follow-up visits,
      if your transplant doctor decides it is needed. It may be life-threatening to leave the study
      after you have begun to receive the study drugs but before you receive the stem cells.

      This is an investigational study. Ibritumomab tiuxetan, rituximab, bendamustine, and
      fludarabine are FDA approved and commercially available for the treatment of lymphoma. The
      dose of ibritumomab tiuxetan in this study is designed to be higher than the FDA approved
      dose. The use of ibritumomab tiuxetan and bendamustine in combination with the other study
      drugs and a stem cell transplant for the treatment of lymphoma is investigational.

      Up to 20 patients will take part in this study. All will be enrolled at MD Anderson.
    

Intervention name(s): Rituximab; 111In Ibritumomab; Planar Scintigraphy Imaging; 90Y IbritumomabTiuxetan; Fludarabine; Bendamustine; Thymoglobulin; Tacrolimus; Methotrexate; Mycophenolate; G-CSF; Stem Cell Transplantation
Intervention type(s): Drug; Drug; Procedure; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure
Intervention description(s): 250 mg/m2 by vein preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively on Days -22 and -14.; (5.0 mCi +/- 10% of 111In) by vein immediately following the infusion of rituximab on Day -22.; Day -22, -21 to -16: Planar scintigraphy whole-body imaging started on Day -22 post 111In Ibritumomab infusion prior to voiding, and repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Whole-body planar scintigraphy imaging will be repeated between 22-26 hours, then between 70-74 hours, and later between 142-146 hours post 111In Ibritumomab injection.; Calculated to deliver not below 10 Gy to normal organs (liver, lungs, kidneys) by vein post rituximab on Day -14.; 30 mg/m2 intravenously on Days -5, -4, and -3.; 130 mg/m2 intravenously on D-5, -4 and -3.; 1 mg/kg (based on actual body weight) on Days -2 and -1 will be administrated to patients receiving a cord blood (CB) and a matched unrelated donor (MUD).; Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no Graft versus Host Disease (GVHD) is present.
For patients receiving cord blood (CB) graft, the Graft versus Host Disease (GvHD) prophylaxis will be with Tacrolimus. Tacrolimus will start on D-2 administrated at starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on D -2 and will be tapered around Day +180 if no GvHD is present.; 5 mg/m2 by vein on Day +1, +3 and +6. Patients receiving an unrelated graft will also be given methotrexate on Day +11 after the transplant.; 15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth administered from Days -3 to +45 and then tapered to end by day 100 if there is no Graft versus Host Disease (GVHD).; 5 mcg/kg/day subcutaneously beginning Day +7 for patients receiving related and matched unrelated donor (MUD) grafts and on Day 0 for patients receiving a cord blood (CB). G-CSF will continue until the absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.; Stem Cell Transplantation on Day 0
Other intervention name(s): Rituxan; Zevalin; Zevalin; Fludarabine Phosphate; Fludara; Bendamustine Hydrochoride; Bendamustine HCL; CEP-18083; SDX-105; Treanda; ATG; Antithymocyte Globulin; Prograf; MMF; Mycophenolate Mofetil; CellCept; Filgrastim; Neupogen; Allogeneic transplantation
Intervention MeSH terms: Mycophenolic Acid; Rituximab; Methotrexate; Fludarabine; Fludarabine phosphate; Bendamustine Hydrochloride; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Chronic lymphocytic leukemia; Lymphoma; CD20+ lymphoid malignancies; Diffuse large B-cell lymphoma; Allogeneic transplantation; Rituximab; Rituxan; In ibritumomab; Y ibritumomab; Zevalin; Fludarabine Phosphate; Fludara; Bendamustine Hydrochloride; Bendamustine HCL; CEP-18083; SDX-105; Treanda; Stem Cell Transplantation; Planar Scintigraphy; Spect Scan; Single Photon Emission-Computed Tomography; CT Scan; Computed Tomography; G-CSF; Filgrastim; Neupogen; Thymoglobulin; ATG; Antithymocyte Globulin; Methotrexate; Mycophenolate; MMF; Mycophenolate Mofetil; CellCept; Tacrolimus; Prograf