Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab

• ClinicalTrials.gov Identifier: NCT01456351
• Recruitment Status: Completed
• First Posted: October 20, 2011
• Last Update Posted: February 12, 2013
• Sponsor: University of Giessen
• Information provided by (Responsible Party): Jurgen Barth, University of Giessen

Tracking Information

• First Submitted Date: October 11, 2011
• First Posted Date: October 20, 2011
• Last Update Posted Date: February 12, 2013
• Study Start Date: September 2003
• Actual Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2011)

Event Free Survival [ Time Frame: Observation till event or death, minimum 1 year ]

From date of randomization until the date of first documented progression, date of detection of a secondary malignancy or date of death from any cause, whichever came first. Minimum 1 year

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 19, 2011)

Remission Rates [ Time Frame: Observation till event or death, minimum 1 year ]

From date of randomization until the date of first documented progression, date of detection of a secondary malignancy or date of death from any cause, whichever came first. Minimum 1 year

• 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 Fludarabine Plus Rituximab
• Official Title: Prospective Randomised Multicenter Study for Therapy Optimization of Recurrent, Progressive Low Grade Non-Hodgkin Lymphomas and Mantle Cell Lymphomas
• 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.
• Detailed Description: Not Provided
• 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's Lymphoma
• Mantle Cell Lymphoma

Intervention

• Drug: Bendamustine plus Rituximab
  Bendamustine 90 mg/m² d 1+2 + Rituximab 375 mg/m² d 1 q4w for maximum 6 cycles
• Drug: Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w
  Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w for maximum 6 cycles

Study Arms

• Experimental: Bendamustine plus Rituximab
  Bendamustine 90 mg/m² d 1+2 + Rituximab 375 mg/m² d 1 q4w
  Intervention: Drug: Bendamustine plus Rituximab
• Active Comparator: Fludarabine plus Rituximab
  Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w
  Intervention: Drug: Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w

• Publications *: 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. Erratum In: Lancet Oncol. 2016 Jan;17(1):e6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 19, 2011): 230
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2010
• Actual Primary Completion Date: August 2010 (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
• 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

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: NCT01456351
• Other Study ID Numbers: NHL 2-2003
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jurgen Barth, University of Giessen
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Giessen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Giessen
• Verification Date: February 2013