Clinical Trials /

Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT)

NCT01490723

Description:

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.

Related Conditions:
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Zevalin</span>-Containing Nonmyeloablative Conditioning for <span class="go-doc-concept go-doc-intervention">Stem Cell</span> Transplantation (SCT)

Title

  • Brief Title: Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT)
  • Official Title: Dose-Intense Yttrium-90 Ibritumomab Tiuxetan (Zevalin)-Containing Non-Myeloablative Conditioning for Allogeneic Stem Cell Transplantation in B-cell Malignancies
  • Clinical Trial IDs

    NCT ID: NCT01490723

    ORG ID: 2011-0393

    Trial Conditions

    Leukemia

    Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    Rituximab Rituxan Yttrium-90 Ibritumomab + Chemo
    111In Ibritumomab Zevalin Yttrium-90 Ibritumomab + Chemo
    90Y IbritumomabTiuxetan Zevalin Yttrium-90 Ibritumomab + Chemo
    Fludarabine Fludarabine Phosphate, Fludara Yttrium-90 Ibritumomab + Chemo
    Bendamustine Bendamustine Hydrochoride, Bendamustine HCL, CEP-18083, SDX-105, Treanda Yttrium-90 Ibritumomab + Chemo
    Thymoglobulin ATG, Antithymocyte Globulin Yttrium-90 Ibritumomab + Chemo
    Tacrolimus Prograf Yttrium-90 Ibritumomab + Chemo
    Methotrexate Yttrium-90 Ibritumomab + Chemo
    Mycophenolate MMF, Mycophenolate Mofetil, CellCept Yttrium-90 Ibritumomab + Chemo
    G-CSF Filgrastim, Neupogen Yttrium-90 Ibritumomab + Chemo

    Trial Purpose

    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.

    Trial Arms

    Name Type Description Interventions
    Yttrium-90 Ibritumomab + Chemo Experimental Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment. Rituximab, 111In Ibritumomab, 90Y IbritumomabTiuxetan, Fludarabine, Bendamustine, Thymoglobulin, Tacrolimus, Methotrexate, Mycophenolate, G-CSF

    Eligibility Criteria

    Inclusion Criteria:

    1. 18 to 70 years of age.

    2. Patients with the following CD20+ lymphoid malignancies who are eligible for
    allogeneic transplantation: a. Relapsed or refractory follicular lymphoma; b.
    Relapsed or refractory or high risk mantle cell lymphoma (hi ki67; blastic); c.
    Recurrent or refractory marginal zone; d. Recurrent or refractory CLL/small
    lymphocytic lymphoma; e. Double-hit lymphoma; f. Diffuse large B cell lymphoma; g.
    Richter's patients; or h. Refractory or recurrent Burkitts.

    3. Patients who meet criterion #2 or have any of the following are eligible: a. Less
    than PR to salvage chemotherapy; b. Kinetic failure; c. Having received more than 3
    lines of therapy; d. Failure to mobilize autologous stem cell; e. 10% or more marrow
    involvement; f. 6 months post autologous stem cell transplant.

    4. Patients must have a fully-matched related donor or a matched unrelated donor
    identified. Double cord (at least 4/6 matched) can be used if no adult matched donor
    is available.

    5. Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.

    6. Left ventricular EF >/= 45% with no uncontrolled arrythmias or symptomatic heart
    disease.

    7. FEV1, FVC >/= 60% and corrected DLCO >/= 60%.

    8. Serum creatinine </=1.6 mg/dL. Serum bilirubin < 2 mg/dL (unless due to Gilbert's
    Syndrome).

    9. SGPT < 2 X upper limit of normal.

    10. Men and women of reproductive potential must agree to follow accepted birth control
    methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with
    spermicide, condom with spermicide, or abstinence) for the duration of the study.

    11. Negative Beta HCG test within 30 days in a woman with child bearing potential defined
    as not post-menopausal for 12 months or no previous surgical sterilization).
    Pregnancy testing is not required for post-menopausal or surgically sterilized women.

    Exclusion Criteria:

    1. Patient with active CNS involvement with lymphoid malignancy.

    2. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.

    3. Patients with other malignancies diagnosed within 2 years prior to study
    registration. Skin squamous or basal cell carcinoma are exceptions.

    4. Active bacterial, viral or fungal infections.

    5. History of stroke within 6 months prior to study registration.

    6. A prior allogeneic stem cell transplant.

    7. Patient has received other investigational drugs within 3 weeks before study
    registration.

    8. Presence of circulating malignant lymphoid cells or bone marrow with lymphoma that
    constituted more than 25% of the cellular elements.

    9. Serious nonmalignant or malignant disease or psychiatric illness, which, in the
    opinion of the investigator would compromise protocol objectives or interfere with
    participation.

    10. Patients who are breast-feeding.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 70 Years

    Eligible Gender: Both

    Primary Outcome Measures

    100 Day Treatment-Related Mortality (TRM)

    Secondary Outcome Measures

    Overall Survival (OS)

    Trial 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

    Allogeneic 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