Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies
Condition: Lymphoma; Leukemia
MeSH terms: Lymphoma; Leukemia; Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The goal of this clinical research study is to see if low intensity chemotherapy given
      together with the new drug 90Y Zevalin, followed by a transplant of blood or marrow stem
      cells from a donor can increase the length of remission in patients with leukemia and
      lymphoma. The safety of this treatment will also be studied.
    

Detailed description: 
      Rituxan is an antibody made from human and mouse protein. It reacts with a certain antigen on
      lymphoma cells and causes the body's immune system to destroy the lymphoma cells. 90Y Zevalin
      and 111In Zevalin are murine-based antibodies combined with a radioactive agent that can also
      destroy lymphoma cells. Unlike Rituxan, 90Y Zevalin cannot be traced by regular scanning and
      requires indium to determine its distribution through the body.

      Before treatment starts, patients will have a physical exam, including blood tests and urine
      tests. Women who are able to have children must have a negative blood pregnancy test. Bone
      marrow samples will be taken. For bone marrow sampling, a large needle is placed in the
      hipbone after it has been numbed. The bone marrow is then withdrawn through the needle.
      Patients will have a chest x-ray, computed tomography (CT) scans, an EKG, and tests of lung
      function.

      Blood tests, urine tests, bone marrow sampling, and x-rays will be done as needed to track
      the effects of the transplant. Patients will have transfusions of blood and platelets as
      needed. Blood tests will be done daily while patients are in the hospital.

      Patients in this study will receive an unlabeled antibody form of Y2B8 called rituxan by vein
      followed by a dose of 111In Zevalin by vein. 111In Zevalin includes the radioactive agent
      indium, which shows up when patients have x-rays or scans. The scans can show where and how
      fast the drug travels 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 see
      if it is safe to give 90Y Zevalin on an outpatient basis. A scan will be taken 48 to 72 hours
      after 111In Zevalin is given.

      If the radiation in the 111In Zevalin is not a threat to normal organs and bone marrow,
      patients may receive 90Y Zevalin. Seven days after the 111In Zevalin injection, patients will
      receive a second dose of rituxan followed by a dose of 90Y Zevalin.

      Patients will also receive fludarabine and cyclophosphamide daily for 3 days. All of the
      chemotherapy drugs will be given through a catheter (plastic tube) that extends into the
      large chest vein. The catheter will be left in place throughout treatment. When chemotherapy
      is finished, blood stem cells from a donor will be given through the catheter. Granulocyte
      colony-stimulating factor (G-CSF or GCSF), a hormone that helps the production of blood
      cells, will be injected under the skin once a day until the neutrophil counts recover in the
      blood. Patients will receive methotrexate for 3 days post transplant and tacrolimus for 6
      months or more to prevent graft versus host disease.

      All patients will have complete checkups, including blood and urine tests 2 or 3 times during
      the first 12 weeks of the study. Tumors will be measured by CT or MRI and gallium scans.
      Patients will be asked to fill out a survey about quality of life issues (maintaining normal
      routine, family life, social life, pain). It takes about half an hour to fill out the survey.
      A bone marrow sample may be taken. A test of heart function will be done. Checkups and tests
      will be done every 3 months for 1 year and then every 6 months for 4 more years.

      Treatment will be given in the hospital at M. D. Anderson. Patients will need to stay in the
      hospital for about 3 to 4 weeks. Patients must stay in the Houston area for about 100 days
      after the transplant. After that, patients will need to return to Houston from time to time
      for blood tests, urine tests, and other exams.

      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. About 70 patients
      will take part in this study. All will be enrolled at M. D. Anderson.
    

Intervention name(s): Zevalin Radioimmunotherapy; Rituximab; Fludarabine; Cyclophosphamide; Allogeneic Stem Cell Transplantation
Intervention type(s): Drug; Drug; Drug; Drug; Procedure
Intervention description(s): Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg; 250 mg/m^2 on day 1 and day 8; 30 mg/m^2/day for 3 days; 750 mg/m^2/day for 3 days, given on the same days as fludarabine, at 4-hour intervals; Allogeneic stem cell transplantation 2 days after chemotherapy
Other intervention name(s): 90Y Zevalin; Rituxan; Fludarabine phosphate; Fludara; Cytoxan; Neosar; ASCT
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Lymphoma; Lymphoid Malignancy; Cyclophosphamide; Cytoxan; Neosar; Fludarabine; Fludarabine Phosphate; Fludara; Rituximab; Rituxan; Zevalin; Indium Zevalin; 90Y Zevalin; CD-20-positive; B-cell Lymphoma; CD-20-positive B-cell Lymphoma; NHL; CLL; Chronic Lymphocytic Leukemia; Allogeneic Stem Cell Transplantation; ASCT