High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

• Treatment-related mortality [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
  Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.
• Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
• Response rates [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
• Engraftment and hematopoietic toxicity [ Time Frame: Up to day 100 ] [ Designated as safety issue: Yes ]
  Engraftment assessed by need for blood transfusion support. Toxicity graded in severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.

• Treatment-related mortality [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
• Overall survival [ Time Frame: At 1, 3, 6, 12, 18, and 24 months and annually thereafter ] [ Designated as safety issue: No ]
• Response rates [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
• Engraftment and hematopoietic toxicity [ Time Frame: Daily from date of transplant through engraftment (typically less than 3 weeks), then weekly until approximately 12 weeks after transplant. ] [ Designated as safety issue: Yes ]
  Engraftment assessed by need for blood transfusion support. Toxicity graded in severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.
• Estimation of absorbed radiation doses to normal organs, marrow and tumor [ Time Frame: After test dose of indium In 111 ibritumomab tiuxetan (24-48 hours following test dose) ] [ Designated as safety issue: No ]
  Gamma camera images taken within 24-48 hours following test dose, plus up to 3 additional timepoints if needed.

This phase II trial studies the side effects and how well giving high-dose yttrium-90 (Y-90)-ibritumomab tiuxetan (anti-CD20) followed by fludarabine phosphate, low-dose total body irradiation (TBI), and donor peripheral blood stem cell transplant (PBSCT) works in treating patients with relapsed or refractory aggressive B-cell lymphoma. 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

OBJECTIVES:

I. To assess the safety and efficacy of 1.5 mCi/kg (max 120 mCi) 90Y-Ibritumomab tiuxetan (yttrium Y 90 ibritumomab tiuxetan) (anti-CD20) combined with fludarabine (fludarabine phosphate) (30 mg/m^2 x 3) and 2 Gy total body irradiation followed by human leukocyte antigens (HLA) matched allogeneic hematopoietic transplantation for patients with relapsed or refractory aggressive B-cell lymphoma.

OUTLINE:

Patients receive a dosimetry test dose of indium In 111 ibritumomab tiuxetan intravenously (IV) within four weeks prior to transplant and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV on day -14 prior to transplant. Both ibritumomab tiuxetan infusions may be preceded by rituximab IV, depending on results of blood tests to determine rituximab concentration. Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56 with taper to day 180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate mofetil PO BID on days 0-27 (related donor) or PO thrice daily (TID) on days 0-40 with taper to day 96 (unrelated donor).

After completion of study treatment and assessments through ~day 100 following transplant, patients are followed up at 1, 3, 6, and 12 months and then annually thereafter.

• Post-transplant Lymphoproliferative Disorder
• Recurrent Adult Burkitt Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Adult Diffuse Mixed Cell Lymphoma
• Recurrent Adult Grade III Lymphomatoid Granulomatosis
• Recurrent Adult Immunoblastic Large Cell Lymphoma
• Recurrent Adult Lymphoblastic Lymphoma

• Drug: fludarabine phosphate
  Given IV
  Other Names:

  • 2-F-ara-AMP
  • Beneflur
  • Fludara
• Radiation: total-body irradiation
  Undergo TBI
  Other Name: TBI
• Radiation: yttrium Y 90 ibritumomab tiuxetan
  Given IV
  Other Names:

  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan
• Procedure: allogeneic hematopoietic stem cell transplantation
  Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter)
• Drug: cyclosporine
  Given PO
  Other Names:

  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
• Drug: mycophenolate mofetil
  Given PO
  Other Names:

  • Cellcept
  • MMF
• Biological: rituximab
  Given IV prior to yttrium Y 90 ibritumomab tiuxetan
  Other Names:

  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
• Radiation: indium In 111 ibritumomab tiuxetan
  Given IV
  Other Name: IDEC-In2B8

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 R-CHOP, double hit lymphoma, MYC+ lymphoma, persistent 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 < 1.5mg/dL with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5mg/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
• Patients must be >= 18 years old

Exclusion Criteria:

• Systemic anti-lymphoma therapy given within 30 days prior to therapeutic 90Y-ibritumomab tiuxetan dose
• Inability to understand or give an informed consent
• 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)
• Altered biodistribution (determined following trace-labeled 111In-ibritumomab tiuxetan dose)