Clinical trial NCT00785330: Allo-hNHL (FluBuCy)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin's Lymphoma
Keywords: rituximab
Non-Hodgkin's lymphoma
diffuse large B cell lymphoma
peripheral t cell lymphoma
graft-versus-host disease
graft-versus-lymphoma effect
allogeneic haematopoietic stem cell transplantation
relapsed or primary progressive aggressive Non-Hodgkin's lymphoma
Lead sponsor: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Sponsor class: OTHER
Collaborators: name: University Hospital Goettingen
name: German High-Grade Non-Hodgkin's Lymphoma Study Group
First posted: 2008-11-05
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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:

B-NHL:

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

T-NHL:

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

Eligibility criteria: Inclusion Criteria:

* histology proven aggressive non Hodgkin's lymphoma and
* primary progressive disease or
* early relapse after less than 12 month of remission duration and at least one risk factor according to the international prognostic index (IPI or
* relapse or progression after high dose chemotherapy and autologous transplantation or
* relapse or progression and lack of an autologous stem cell product.

Exclusion Criteria:

* severe comorbidity or impaired organ function
* hypersensitivity to used drugs
* HIV positivity
* active hepatitis
* other active malignant disease

Primary outcomes:
measure: 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
timeFrame: One year after allogeneic stem cell transplantation
Secondary outcomes:
measure: progression free survival, progression rate, non-relapse mortality, rate of grade 3-4 infectious adverse event, chronic GVHD
timeFrame: one and three years after allogeneic SZT
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Würtenberg
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg
state: Hessen
city: Homburg
country: Germany
facility: Universitätsklinikum und Poliklinik
state: Saarland
city: Göttingen
country: Germany
facility: University Hospital Goettingen
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Münster
country: Germany
facility: KMT-Zentrum Medizinische Klinik A
Study officials:
affiliation: Asklepios Klinik St. Georg
name: Bertram Glass, Prof. MD.
role: STUDY_DIRECTOR
References:
citation: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Gorlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. doi: 10.1016/S1470-2045(14)70161-5. Epub 2014 May 11.