Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT)
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia
Intervention: Rituximab; 111In Ibritumomab; Planar Scintigraphy Imaging; 90Y IbritumomabTiuxetan; Fludarabine; Bendamustine; Thymoglobulin; Tacrolimus; Methotrexate; Mycophenolate; G-CSF; Stem Cell Transplantation
Intervention description: 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
Intervention MeSH terms: Mycophenolic Acid; Rituximab; Methotrexate; Fludarabine; Fludarabine phosphate; Bendamustine Hydrochloride; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
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

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.
    

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.