Allogeneic Hematopoietic Stem Cell Transplantation After Reduced-intensity Conditioning for Relapsed Follicular Lymphoma
Condition: Lymphoma, Follicular; Stem Cell Transplantation
MeSH terms: Lymphoma; Lymphoma, Follicular
Study type: Interventional
Phase: Phase 2

Summary: 
      This trial will evaluate the efficacy and the safety of a strategy of allogeneic stem cell
      transplantation including Rituximab in the conditioning regimen for the treatment of relapsed
      follicular lymphoma. The rationale for using Rituximab relies on a better control of the
      disease and a better prophylaxis of the graft versus host disease.
    

Detailed description: 
      Follicular lymphomas are chemosensitive neoplasms characterized by a relentless succession of
      remissions and relapses when treated with conventional chemotherapy. The successive periods
      of remission are of shorter duration and patients invariably die of their disease. At first
      line, patients are treated with conventional chemotherapy. At first relapse, intensive
      chemotherapy with autologous stem cell transplantation (SCT) is often proposed.

      Allogeneic hematopoietic stem cell transplantation after reduced-intensity conditioning
      (RIC-allo) is an option for patients relapsing after autologous SCT, allowing long-term
      progression free survival of 50 to 60%. The toxic mortality related to severe acute graft
      versus host disease (GVHD) remains a critical issue. The goal of our study is to test in a
      multicentric approach a strategy of RIC-allo including rituximab in order to reduce the
      incidence of acute GVHD.

      Around half of patients with relapsed or refractory follicular lymphomas treated with
      allogeneic SCT achieve long-term progression free survival whatever the conditioning regimen.
      Because the median age of patients with follicular lymphoma is 55 years, a reduced intensity
      conditioning is the most appropriate option in this setting. The outcome of patients with a
      chemoresistant disease is usually poor because of a high toxic mortality. As a consequence,
      only patients with a chemosensitive disease will be included in this study. To further reduce
      the toxic mortality, it is critical to reduce the incidence of severe acute GVHD. A low
      incidence of acute GVHD could be obtained by the use of Rituximab before and after the
      transplantation as reported by the MD Anderson's experience in several hematological
      malignancies including follicular lymphoma. Their results are impressive in patients with
      follicular lymphoma with long-term survival of 85%. The favored hypothesis is a depletion of
      patient and donor B cells reducing the presentation of minor histocompatibility alloantigens.
      The benefit of Rituximab could also be explained by its anti-lymphoma effects that could
      compensate the putative reduction of a graft versus lymphoma effect due to a better control
      of GVHD.

      The primary objective is to estimate 2-year overall survival in this setting.
    

Intervention name(s): Reduced_intensity conditioning
Intervention type(s): Drug
Intervention description(s): The conditioning regimen is composed of Fludarabine (30 mg/m2) and Cyclophosphamide (750 mg/m2), both administered intravenously at Days -5, -4, -3 with Day 0 being the day of transplantation. Rituximab will be administered intravenously at 375 mg/m2 at Day -13 and 1000 mg/m2 at Days -6, +1, +8. Tacrolimus and low-doses of methotrexate will be used for prophylaxis of GVHD.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Allogeneic hematopoietic stem cell transplantation; Reduced-intensity conditioning; Chemosensitive relapsed follicular lymphoma