Yttrium-90 Ibritumomab Tiuxetan (Zevalin) With BEAM in Relapsed Low Grade B-Cell Lymphoma
Condition: B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The objective of this study is to evaluate the efficacy and the safety of Zevalin-BEAM
      preparative regimen before autologous stem cell transplantation (ASCT) as measured by the
      event free survival (EFS).

      The goal is to obtain a 15% increase of EFS at 2 years.
    

Detailed description: 
      The indolent course of the low-grade B-cell lymphoma is thus characterized by multiple
      remissions and relapses with ever-shortening "time to progression" intervals, and by
      ultimately becoming refractory to treatment. In this situation of recurrences, intensive
      therapy including high-dose chemotherapy or chemo-radiotherapy followed by autologous
      hematopoietic stem cell transplantation appears as a therapeutic option. With the use of
      peripheral blood stem cell, the autologous stem cell transplantation (ASCT) procedure has
      become easier and cheaper, and it has a mortality rate of below 5% and manageable morbidity.
      EBMT registry data or institution driven studies have shown an improvement in event free
      survival when compared to chemotherapy in relapsing patients. Recently Schouten et al
      reported in a randomized study a significant benefit in survival for patients submitted in
      relapse to ASCT. Consolidation with ASCT has been studied in first line treatment and showed
      a significant improvement in survival in one randomized study. BEAM regimen is a referent
      high-dose chemotherapy used in intensive therapy followed by ASCT in the treatment of
      malignant lymphoma. It could therefore be considered for patients with indolent lymphoma if
      it could be shown to improve survival. In most studies the conditioning regimen was
      associating chemotherapy and Total Body Irradiation (TBI) for indolent lymphoma as it is very
      sensitive to even low dose of radiotherapy. TBI however is time consuming and technically not
      available in all transplant centers and associated with some long term toxicities; a search
      for more specific targeted irradiation has been a goal for several years.

      Recently, a new preparative regimen for older patients with aggressive CD20-positive B-cell
      lymphoma utilizing standard-dose 0.4 mCi/kg 90Y ibritumomab tiuxetan combined with high-dose
      BEAM followed by ASCT showed a CR rate of 92% with a follow-up of 9 months. Finally,
      high-dose radioimmunotherapy with 90Y ibritumomab tiuxetan and high-dose
      cyclophosphamide/etoposide followed by ASCT for poor-risk or relapsed B-cell NHL have been
      reported, with a 2-year DFS of 80%. The use of conventional dose of Yttrium did not need
      heavy radioprotection procedures, and can be widely distributed in transplant centers.

      Overall toxicities were comparable to standard autologous transplantation conditioning
      regimens, and the combined treatment was well tolerated. The hematological reconstitution
      after transplantation occurred without delay, except in two cases than in control-based
      high-dose chemotherapy alone population. Mucositis and neutropenic fever were reported
      without increase of severity. Nonhematological adverse events have been observed, three
      interstitial pneumonitis, mild abnormalities on liver or kidney function tests, except one
      case of veno-occlusive disease, and 4 fatal infection (disseminated aspergillosis with a
      brain abscess, streptococcal sepsis, staphylococcal sepsis, and disseminated varicella
      zoster).

      Therefore, all these data support a phase II trial evaluating efficacy and toxicities in
      patients with low grade B-Cell lymphoma of a new preparative regimen combining a standard
      dose 90Y ibritumomab tiuxetan and high-dose BEAM chemotherapy followed by ASCT.
    

Intervention name(s): Zevalin plus BEAM
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: lymphoma; chemotherapy; Zevalin ( Yttrium-90 Ibritumomab Tiuxetan)