High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma
Condition: Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma
MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; Recurrence
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation; Cyclosporine; Fludarabine Phosphate; Indium In-111 Ibritumomab Tiuxetan; Mycophenolate Mofetil; Pharmacological Study; Rituximab; Total-Body Irradiation; Yttrium Y-90 Ibritumomab Tiuxetan; Fludarabine
Intervention description: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter); Given PO; Given IV; Given IV; Given PO; Correlative studies; Given IV prior to yttrium Y 90 ibritumomab tiuxetan; Undergo TBI; Given IV; Given IV
Intervention MeSH terms: Vidarabine; Cyclosporine; Mycophenolic Acid; Rituximab; Antineoplastic Agents, Immunological; Fludarabine; Fludarabine phosphate; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Cyclosporins
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
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well high-dose yttrium-90
      (Y-90)-ibritumomab tiuxetan (anti-cluster of differentiation [CD]20) followed by fludarabine
      phosphate, low-dose total body irradiation (TBI), and donor peripheral blood stem cell
      transplant (PBSCT) work in treating patients with aggressive B-cell lymphoma that has
      returned after a period of improvement (relapsed) or has not responded to previous treatment
      (refractory). Radiolabeled monoclonal antibodies, such as Y-90-ibritumomab tiuxetan, can find
      cancer cells and carry cancer-killing substances to them with less effect on normal cells.
      Giving chemotherapy, such as fludarabine phosphate, and TBI before a donor PBSCT helps stop
      the growth of cancer cells. It may also stop the patient's immune system from rejecting the
      donor's stem cells. However, high-dose radiolabeled antibodies also destroy healthy blood
      cells in the patient's body. When healthy stem cells from a donor are infused into the
      patient (stem cell transplant), they may help the patient's body replace these blood cells.
      Giving high-dose Y-90-ibritumomab tiuxetan followed by fludarabine phosphate, TBI, and donor
      PBSCT may be an effective treatment for patients with B-cell lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of aggressive B-cell lymphoma
             (diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL], etc.) expressing the
             CD20 antigen and have failed at least one prior standard systemic therapy

          -  Patients must have relapsed after high-dose therapy and autologous transplantation or
             be ineligible for high-dose therapy and autologous transplantation; patients that have
             failed autologous transplantation are those with persistent disease > 30 days after
             transplant; those ineligible for autologous transplant include those with
             chemoresistant disease (i.e., patients who have not achieved a partial response or
             better with their most recent chemotherapy regimen), are expected to have a poor
             outcome from autologous transplant (e.g., DLBCL relapsing within one year of
             rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate,
             prednisone [R-CHOP]-like chemotherapy, double hit lymphoma, v-myc myelocytomatosis
             viral oncogene homolog (avian) positive [MYC+] lymphoma, persistent positron emission
             tomography [PET] positivity after chemotherapy), are unable to collect sufficient or
             tumor-free autologous stem cells per Seattle Cancer Care Alliance (SCCA) standard
             practice, are unable to tolerate the high-dose autologous conditioning regimens, or
             who refuse a high-dose autologous transplant regimen

          -  Creatinine (Cr) < 2.0

          -  Bilirubin < 1.5 mg/dL with the exception of patients thought to have Gilbert's
             syndrome, who may have a total bilirubin above 1.5 mg/dL

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limit of
             normal (ULN)

          -  Patients must have an expected survival without treatment of > 60 days and must be
             free of major infection including human immunodeficiency virus (HIV)

          -  Patients must have an HLA-identical related or HLA-matched unrelated donor

        Exclusion Criteria:

          -  Receipt of systemic anti-lymphoma therapy withinthe following intervals prior to the
             therapeutic 90Y-ibritumomab tiuxetan dose:

               -  < 30 days for intravenously-administered cytotoxic chemotherapy and/or monoclonal
                  antibodies

               -  < 5 half-lives for all other anti-cancer agents (e.g., targeted therapies,
                  corticosteroids, immunomodulatory agents, etc.)

          -  Inability to understand or give an informed consent

          -  Active central nervous system lymphoma

          -  Pregnancy

          -  Fertile men or women unwilling to use contraceptive techniques during and for 12
             months following treatment

          -  Southwest Oncology Group (SWOG)/Eastern Cooperative Oncology Group (ECOG) performance
             score >= 2

          -  High-dose chemotherapy or external beam radiation therapy to lung, liver, or kidneys >
             20 Gy within the previous 100 days prior to therapeutic 90Y-ibritumomab tiuxetan dose

          -  Medical condition that would contraindicate allogeneic transplantation as per standard
             practice guidelines (e.g., impaired cardiopulmonary function, hepatitis, etc)