Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Relapsed or Refractory Follicular Lymphoma
Condition: Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the rate and duration of complete remission and
      molecular response in patients with relapsed/refractory follicular lymphoma, using a combined
      treatment with rituximab plus chemotherapy followed by in vivo purged peripheral blood stem
      cells (PBSC) mobilization and autotransplant.
    

Detailed description: 
      Autologous stem cell transplantation has been shown effective in the long-term control of
      follicular lymphoma. Lymphoma, however, can progress after high-dose treatments. Lymphoma
      cells have been proved to contaminate bone marrow and peripheral blood stem cells (PBSC)
      collections and may contribute to relapse after autotransplant. The presence in peripheral
      blood and marrow of PCR-detectable cells bearing the bcl-2 rearrangement appeared to be a
      surrogate marker of disease and the achievement of a bcl-2 negative status is associated with
      a lower risk of recurrence. Several methods have been attempted to abolish graft
      contamination: in vitro treatment with cytotoxic agents, in vitro treatment with anti-B-cell
      monoclonal antibodies and complement, immunomagnetic beads, positive selection of CD34+
      cells. All these techniques usually produce loss of cells, are time-consuming and expensive,
      and neoplastic depletion is often partial with residual polymerase chain reaction
      (PCR)-positive cells in the graft.

      In the last years the chimeric anti-CD20 monoclonal antibody Rituximab has been shown to be
      an effective therapeutic option for low-grade lymphoma. Owing to the different mechanism of
      action, the synergism with cytotoxic agents, and the non-overlapping toxicity, Rituximab is
      an ideal drug for combination with chemotherapy. On this basis, Rituximab has been used
      during mobilisation procedures as a tool to obtain in vivo purging and collection of
      lymphoma-free progenitor cells. In addition, several studies have demonstrated that the
      efficiency of peripheral blood stem cells (PBSC) harvested is not adversely affected by
      Rituximab and that engraftment and all parameters of hematopoietic recovery are not
      compromised. The incorporation of Rituximab into sequential high-dose therapy programs
      produced high rates of clinical and molecular remission in patients with indolent lymphoma,
      indicating that the antibody has an additive effect on chemotherapy.
    

Intervention name(s): Immunochemotherapy, in vivo purging and autrotransplant
Intervention type(s): Procedure
Intervention description(s): 2-4 courses every 3 weeks with rituximab 375 mg/m^2 on day 1, vincristine 1.4 mg/m^2 on day 2 and cyclophosphamide 400 mg/m^2 on days 2-6. Courses were started if granulocytes >1.5 · 10^9/l. The phase of peripheral blood stem cells (PBSC) mobilization coupled rituximab 375 mg/m^2 on days 1 and 9 with high-dose cytarabine (AraC) 2 g/m^2 every 12 hours on days 2 and 3. Granulocyte colony-stimulating factor (G-CSF)(5 mcg/kg/day subcutaneously) was administered from day 6. High-dose chemotherapy with autotransplant consisted of BEAM [carmustine (BCNU), etoposide, Cytarabine (AraC), melphalan] followed by the infusion of in vivo purged peripheral blood stem cells (PBSC) + 2 consolidation doses of rituximab 375 mg/m^2 on days +14 and +21 after autotransplant.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: follicular lymphoma; rituximab; immunochemotherapy; peripheral blood stem cells (PBSC) mobilization; in vivo purging; autotransplant; bcl-2 rearrangement; molecular response