Bendamustine Plus Rituximab Versus CHOP Plus Rituximab

• ClinicalTrials.gov Identifier: NCT00991211
• Recruitment Status: Completed
• First Posted: October 7, 2009
• Last Update Posted: March 14, 2012
• Sponsor: University of Giessen
• Information provided by (Responsible Party): Jurgen Barth, University of Giessen

Tracking Information

• First Submitted Date: October 6, 2009
• First Posted Date: October 7, 2009
• Last Update Posted Date: March 14, 2012
• Study Start Date: January 2004
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 6, 2009): Progression free survival [ Time Frame: observation 3 years or significant differences between two arms ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: October 6, 2009): Determination and comparison of remission rates, of toxicity, infectious complications, overall survival, EFS, TTNT, capacity of peripheral blood stem cell mobilization [ Time Frame: ongoing ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Hodgkin Lymphomas
• Follicular Lymphomas
• Immunocytomas
• Lymphocytic Lymphomas
• Marginal Zone Lymphomas

Intervention

• Drug: Bendamustine
  Comparison of Bendamustine + Rituximab with CHOP + Rituximab
  Other Name: Ribomustin, Treanda
• Drug: Standard chemotherapy CHOP + Ritiximab
  Cyclophosphamid 750 mg/m² d 1 + Doxorubicin 50 mg/m² d 1 + Vincristin 1,4 mg/m² max. 2 mg d 1 + Prednison 100 mg absolute p.o. d 1-5 + Rituximab 375 mg/m² d 1 q3w as standard Chemotherapy
  Other Names:

  • Endoxan(R), Cyclostin(R) = Cyclophosphamide
  • Adriamycin(R) Doxorubicin
  • Oncovin(R) Vincristine
  • Prednison
  • Rituxan(R), MabThera(R) = Rituximab

Study Arms

• Experimental: Bendamustine + Rituximab
  Bendamustine 90 mg/m² d 1+2 + Rituximab 375 mg/m² d 1 q4w
  Intervention: Drug: Bendamustine
• Active Comparator: CHOP + Rituximab
  Cyclophosphamid 750 mg/m² d 1 + Doxorubicin 50 mg/m² d 1 + Vincristin 1,4 mg/m² max. 2 mg d 1 + Prednison 100 mg absolute p.o. d 1-5 + Rituximab 375 mg/m² d 1 q3w
  Intervention: Drug: Standard chemotherapy CHOP + Ritiximab

Publications *

• 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.
• 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. Erratum In: Lancet. 2013 Apr 6;381(9873):1184.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 6, 2009): 549
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT00991211
• Other Study ID Numbers: NHL 1-2003
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jurgen Barth, University of Giessen
• Original Responsible Party: Dr. Mathias Rummel, Study Group of indolent Lymphomas (StiL)
• Current Study Sponsor: University of Giessen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mathias Rummel, Dr.; Study Group of indolent Lymphom,as (StiL)

• PRS Account: University of Giessen
• Verification Date: October 2009