DSHNHL R3 is a randomized clinical phase II study. The main objective is to estimate the efficacy of rituximab as a prophylactic medication for prevention of graft-versus-host-disease after allogeneic peripheral stem cell transplantation in patients with a high risk relapse of aggressive B-cell Non-Hodgkin's lymphoma. The most important secondary objective is to estimate the efficacy of allogeneic stem cell transplantation in this clinical situation.
Drug: standard GVHD prophylaxis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open, Multicentral, Randomised Phase II Study of Allogene Stem Cell Transplantation After Pretreatment With Fludarabin, Busulfan, Cyclophospahmid and GVHD-Prophylaxis With or Without Rituximab in Patients With Recidivation of High Grade Non-Hodgkin's Lymphoma in Special Risk Situation in the Age of 18 - 65|
- The specific measure that will be used to determine the effect of the intervention(s) or, for observational studies, related to core objectives of the study and receiving the most emphasis in assessment. (a) rate of acute GVHD grade II-IV after one year [ Time Frame: One year after allogeneic stem cell transplantation ] [ Designated as safety issue: Yes ]
- progression free survival, progression rate, non-relapse mortality, rate of grade 3-4 infectious adverse event, chronic GVHD [ Time Frame: one and three years after allogeneic SZT ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2004|
|Estimated Study Completion Date:||April 2014|
|Estimated Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
No Intervention: A
Patients receiving no rituximab as GVHD prophylaxis after allogeneic SZT and only standard GVHD prophylaxis (tacrolimus with aimed serum level of 10 ng / ml and mycophenolat mofetil 2 x 1 g p.o. day 1 to 28 after allogeneic SZT
Drug: standard GVHD prophylaxis
Application of tacrolimus from day -1 with a goal of tacrolimus serum concentration of 10 ng / ml Aplication of mycophenolat mofetil from day +1 to day +28 in a dose of 2 x 1g per day
rituximab in addition to standard GVHD prophylaxis
Patients receiving 375 mg/ m2 of rituximab at weeks 3, 4, 5, 6, 25, 26, 27, 28 after allogeneic stem cell transplantation in addition to standard GVHD prophylaxis (tacrolimus with aimed serum level of 10 ng / ml and mycophenolat mofetil 2 x 1 g p.o. day 1 to 28 after allogeneic SZT
Patients in the age of 18 to 65 years with a high- risk relapse of a histology proven aggressive Non-Hodgkin's-lymphoma are eligible for the trial. Aggressive Non-Hodgkin's lymphoma within this study is defined as:
follicular lymphoma grade III° lymphoblastic (precursor) lymphoma diffuse large cell cell lymphoma any subtype and variant including primary mediastinal lymphoma mantle cell lymphoma, blastic variant
precursor T cell lymphoma peripheral T cell lymphoma, any subtype and variant angioimmunoblastic lymphoma anaplastic large cell lymphoma, any subtype NK / T cell lymphoma High risk relapsed or progressive disease is defined as (a) primary progressive disease, (b) early relapse after less than 12 month of remission duration and at least one risk factor according to the international prognostic index (IPI), (c) relapse or progression after high dose chemotherapy and autologous transplantation, (d) relapse or progression and lack of an autologous stem cell product.
Patients with this type of progression / relapse should receive rituximab plus ifosfamide/carboplatin/etoposide (R-ICE) or rituximab plus dexamethasone/high dose ARA-C/cisplatinum as salvage therapy (recommendation, not part of study medication). In patients biwth T cell lymphoma rituximab may be replaced by alemtuzumab. If at least stable disease is achieved, patients can be definitely included.
With inclusion, patients were randomized to receive either 375 mg/ m2 of rituximab at weeks 3, 4, 5, 6, 25, 26, 27, 28 after allogeneic stem cell transplantation or no additional medication.
Conditioning for transplantation consisted of Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg.
Short-term (day 1 to day 28) mycophenolat mofetil and tacrolimus are used as basis GVHD prophylaxis in all patients. Anti-thymocyte globulin can be used due to the centres decision in patients with unrelated donors
|Heidelberg, Baden-Würtenberg, Germany|
|Marburg, Hessen, Germany|
|Universitätsklinikum und Poliklinik|
|Homburg, Saarland, Germany|
|University Hospital Goettingen|
|Göttingen, Germany, D.37075|
|Asklepios Klinik St. Georg|
|Hamburg, Germany, D-20099|
|KMT-Zentrum Medizinische Klinik A|
|Study Director:||Bertram Glass, Prof. MD.||Asklepios Klinik St. Georg|