Clinical trial NCT00991211: Bendamustine Plus Rituximab Versus CHOP Plus Rituximab
Official title: Prospective Randomised Multicenter Study for Therapy Optimization (First Line) of Advanced Progredient, Low Malignant Non-Hodgkin Lymphomas and Mantle Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Hodgkin Lymphomas
Follicular Lymphomas
Immunocytomas
Lymphocytic Lymphomas
Marginal Zone Lymphomas
Keywords: Comparison
Bendamustine + Rituximab
CHOP + Rituximab
Progression free survival
Overall survival
Toxicity
Safety
Lead sponsor: University of Giessen
Sponsor class: OTHER
First posted: 2009-10-07
Enrollment: 549
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 the first line therapy of low malignant and mantle cell lymphomas with bendamustine plus rituximab is comparable (non inferior) with CHOP plus rituximab with regard to progression free survival (PFS).

Detailed description: The 4 agent chemotherapy (CTX) CHOP (cyclophosphamide, doxorubicin, vincristine prednisone) in combination with the monoclonal anti-CD20 antibody rituximab (CHOP-R) represents a standard CTX for the treatment of lymphomas of high or low malignancy. The combination of bendamustine and rituximab (B-R) is also highly effective with a more advantageous toxicity profile. If B-R could be shown to be non inferior to CHOP-R, this could improve the quality of life of the patient and possibly also the prognosis.

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
* No prior therapy with cytotoxics,interferon or monoclonal antibodies
* Need for therapy, except mantle cell lymphomas
* Stadium III 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, potential curative radiation therapy
* Pretreatment except a unique local delimited radiation (radiation fiel not expanding two adjacent lymph node regions
* 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.

Primary outcomes:
measure: Progression free survival
timeFrame: observation 3 years or significant differences between two arms
Secondary outcomes:
measure: Determination and comparison of remission rates, of toxicity, infectious complications, overall survival, EFS, TTNT, capacity of peripheral blood stem cell mobilization
timeFrame: ongoing
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: StiL Head Office; Justus-Liebig-University
Study officials:
affiliation: Study Group of indolent Lymphom,as (StiL)
name: Mathias Rummel, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rummel MJ et al. Bendamustine Plus Rituximab Is Superior in Respect of Progression Free Survival and CR Rate When Compared to CHOP Plus Rituximab as First-Line Treatment of Patients with Advanced Follicular, Indolent, and Mantle Cell Lymphomas: Final Results of a Randomized Phase III Study of the StiL (Study Group Indolent Lymphomas, Germany). Blood 2009; 114: 405 https://doi.org/10.1182/blood.V114.22.405.405
citation: Rummel MJ et al. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL 1 study. DOI: 10.1200/jco.2012.30.15_suppl.3 Journal of Clinical Oncology 30, no. 15_suppl (May 2012) 3-3.
citation: Rummel MJ et al. Subanalysis of the StiL NHL 1-2003 Study: Achievement of Complete Response with Bendamustine-Rituximab (B-R) and CHOP-R in the First-Line Treatment of Indolent and Mantle Cell Lymphomas Results in Superior Survival Compared to Partial Response. Blood 2012; 120: 2724.
citation: Zohren F, Bruns I, Pechtel S, Schroeder T, Fenk R, Czibere A, Maschmeyer G, Kofahl-Krause D, Niederle N, Heil G, Losem C, Welslau M, Brugger W, Germing U, Kronenwett R, Barth J, Rummel MJ, Haas R, Kobbe G. Prognostic value of circulating Bcl-2/IgH levels in patients with follicular lymphoma receiving first-line immunochemotherapy. Blood. 2015 Sep 17;126(12):1407-14. doi: 10.1182/blood-2015-03-630012. Epub 2015 Aug 3.
citation: Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grunhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Durk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. doi: 10.1016/S0140-6736(12)61763-2. Epub 2013 Feb 20.