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

NCT01434472

Description:

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.

Related Conditions:
  • Burkitt Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Mature B-Cell Lymphoma/Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma
  • Official Title: A Phase II Trial of High-Dose 90Y-Ibritumomab Tiuxetan (Anti-CD20) Followed by Fludarabine and Low-Dose Total Body Irradiation and HLA-Matched Allogeneic Hematopoietic Transplantation for Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 2398.00
  • SECONDARY ID: NCI-2011-01189
  • SECONDARY ID: 2398.00
  • SECONDARY ID: P01CA044991
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT01434472

Conditions

  • 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

Interventions

DrugSynonymsArms
Cyclosporine27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCyaTreatment (radiolabeled antibody, TBI, allogeneic PBSCT)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)
Mycophenolate MofetilCellcept, MMFTreatment (radiolabeled antibody, TBI, allogeneic PBSCT)
RituximabABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Purpose

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.

Detailed Description

      PRIMARY 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 gray (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:

      Beginning 24-48 hours prior to therapy infusion, patients receive rituximab intravenously
      (IV) over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab
      tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)ExperimentalBeginning 24-48 hours prior to therapy infusion, patients receive rituximab IV over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine PO 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 TID on days 0-40 with taper to day 96 (unrelated donor).
  • Cyclosporine
  • Fludarabine Phosphate
  • Mycophenolate Mofetil
  • Rituximab

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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:1 year
Safety Issue:
Description:Based on a one-sample chi-square test with one-sided significance level of five percent. This study will be deemed successful if the 1 year progression-free survival of this highest-risk group of patients is 54% or greater.

Secondary Outcome Measures

Measure:Engraftment and hematopoietic toxicity
Time Frame:Up to day 100
Safety Issue:
Description:Toxicity graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.
Measure:Overall survival
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Response rates
Time Frame:Day 100
Safety Issue:
Description:
Measure:Treatment-related mortality
Time Frame:Day 100
Safety Issue:
Description:Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

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