Clinical trial NCT01456351: Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab
Official title: Prospective Randomised Multicenter Study for Therapy Optimization of Recurrent, Progressive Low Grade Non-Hodgkin Lymphomas and Mantle Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Hodgkin's Lymphoma
Mantle Cell Lymphoma
Keywords: Event free survival
Remission rates
Toxicity
Overall survival
Efficiency costs
Recurrent low grade
Lead sponsor: University of Giessen
Sponsor class: OTHER
First posted: 2011-10-20
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study addresses the question if a therapy with bendamustine plus rituximab is comparable (non inferior) with the well-tried combination of fludarabine plus rituximab with regard to event free survival (EFS) in recurrent low malignant Non-Hodgkin and mantle cell lymphomas.


Eligibility criteria: Inclusion Criteria:

* Patients with histological verified CD20-positive B-Cell-Lymphomas of the following entities:
* Follicular lymphoma grade 1 and 2
* Immunocytoma and lymphoplasmocytic lymphoma
* Marginal zone lymphoma, nodal and generalised
* Mantle cell lymphoma
* lymphocytic lymphoma (CLL without leucaemic characteristics)
* non-specified/classified lymphomas of low malignancy
* Recurrent disease (remission duration minimum 3 months), independent of type or quantity of prior therapies, except of Rituximab containing regimens, or if remission duration is \> 1 year after Rituximab containing regimen, or refractory to prior therapy (progression under therapy or during 3 months after completion), except refractory disease to purin analogs or Bendamustine
* Need for therapy, except mantle cell lymphomas
* Stadium II (bulky disease, 7.5 cm), II or IV
* Written informed consent
* Performance status WHO 0-2
* Histology not older than 6 months

Exclusion Criteria:

* Patients not establishing all above mentioned prerequisites
* Option of a primary, potentially curative radiation therapy
* Patients refractory to Rituximab containing regimens
* Comorbidities excluding a study conform therapy:

heart attack during the last 6 months severe, medicinal not adjustable hypertonia severe functional defects of the heart (NYHA III or IV) lung (WHO grade III or IV) liver or kidney (creatinine \> 2 mg/dl, GOT + GPT or bilirubin 3 x ULN, except caused by lymphoma

* Active auto immunohemolytic anemia (AIHA)
* HIV positive patients
* Active hepatitis infection
* Severe psychiatric diseases
* No compliance or non-compliance to be expected
* Pregnant or breast feeding women
* Anamnestic malignancies or secondary malignancies, not proven
* Cured/curable by surgery

Primary outcomes:
measure: Event Free Survival
timeFrame: Observation till event or death, minimum 1 year
Secondary outcomes:
measure: Remission Rates
timeFrame: Observation till event or death, minimum 1 year
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: StiL Head Office; Justus-Liebig-University
Study officials:
References:
citation: 58. Rummel MJ et al. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas - Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany) Blood 2010; 116: 856
citation: 81. Rummel MJ et al. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas - 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany) Blood 2014; 124:145.
citation: Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study Group Indolent Lymphomas. Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. doi: 10.1016/S1470-2045(15)00447-7. Epub 2015 Dec 5.