Clinical trial NCT00877214: Significance of Duration of Maintenance Therapy With Rituximab in Non-Hodgkin Lymphomas
Official title: Prospective Randomized Multicenter Study in First-line Treatment of Advanced progredIeNT Follicular And Other IndoleNt and Mantle Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Follicular Lymphomas
Immunocytomas
Marginal Zone Lymphomas
Mantle-Cell Lymphomas
Lymphocytic Lymphoma
Non-Hodgkin's Lymphoma
Keywords: Bendamustine
Rituximab
Significance of maintenance therapy
Efficacy and safety
Lead sponsor: University of Giessen
Sponsor class: OTHER
Collaborators: name: Sponsor GmbH
First posted: 2009-04-07
Enrollment: 1272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if an extended maintenance therapy with Rituximab in follicular and a maintenance therapy in other indolent and mantle cell lymphomas has advantages compared to a shorter or no maintenance therapy.

Detailed description: Results from several randomised studies show a clinical benefit of a maintenance therapy with rituximab in follicular lymphomas. The advantage of a maintenance therapy in other indolent and mantle cell lymphomas is - due to the lower incidence of these diseases- not well investigated.

This study tries to determine the significance of an extended maintenance therapy with rituximab in follicular lymphomas and the significance of a maintenance therapy other indolent and mantle cell lymphomas compared to observation.

Eligibility criteria: Inclusion Criteria:

* Patients with histological verified CD20-positive B-Cell-Lymphoma of the following entities:

  * Follicular Lymphoma Grade 1 and 2
  * Lymphoplasmocytic lymphoma / Immunocytoma (Morbus Waldenström) and small cell lymphocytic lymphoma (CLL without leukemic hemogram)
  * Marginal zone lymphoma, nodal and extra nodal
  * Mantle cell lymphoma
* No prior therapy with cytotoxics, interferon or monoclonal antibodies
* Need for therapy, except mantle cell lymphomas
* Stadium III or IV or Stadium with II bulky disease (\> 7 cm diameter, or 3 lesions \> 5 cm)
* General condition WHO 0-2
* Age min. 18 years, max. 80 years
* Negative pregnancy test, contraceptives mandatory for women of child-bearing age
* Actual histology, not older than 6 months required
* Written informed consent

Exclusion Criteria:

* Patients not meeting the inclusion criteria above
* Possibility of a primary radiation therapy with curative intention
* Pretreatment, except a single, localized radiation therapy (radiation field not larger than 2 adjacent lymph node regions)
* Co-morbidities, excluding a therapy according to the protocol:

  * severe, medicinal not adjustable hypertension
  * severe limited capacity of the heart (NYHA III or IV), the lung (WHO-Grade III or IV), the liver and kidneys (creatinin \> 2 mg/dl, GOT and GPT or bilirubin 3 x ULN), except if caused by lymphoma
  * severe, medicinal not adjustable diabetes mellitus
  * active autoimmune disease
  * active infection, requiring antibiotic therapy
* Patients with proven HIV-infection
* Active replicating hepatitis-Infection
* Severe psychiatric diseases
* Lacking or anticipated non-compliance
* Known hypersensitivity against the active components or additives or mouse- proteins
* Pregnant or nursing women
* Patients with a secondary malignancy or malignant disease in his history if, curative surgery can not be doubtless assured .

Primary outcomes:
measure: Progression free survival
timeFrame: 5 years and ongoing
Secondary outcomes:
measure: Remission rate and duration; event free-, progression free-, disease free- and over all survival
timeFrame: 5 years and ongoing
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: StiL Head Office; Justus-Liebig-University
Study officials:
affiliation: University of Giessen
name: Mathias Rummel, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rummel MJ et al. Bendamustin-Rituximab Induction Followed by Observation or Rituximab Maintenance for Newly Diagnosed Patients with Waldenström's Macroglobulinemia: Results From a Prospective, Randomized, Multicenter Study (StiL NHL 7-2008 -MAINTAIN-; ClinicalTrials.gov Identifier: NCT00877214). Blood 2012; 120: 2739. https://doi.org/10.1182/blood.V120.21.2739.2739
citation: Immunochemotherapy with Bendamustine-Rituximab (BR) as induction therapy for indolent lymphomas results in a severe lymphopenia with low CD4+ and CD8+ counts without an increase in atypical infections. First results of the infectious disease (ID) project of a prospective, randomized, multicentre study (StiL NHL 7-2008, MAINTAIN; NCT00877214). Hematol Oncol 2013; 31 (Suppl. 1): 106 https://onlinelibrary.wiley.com/doi/pdf/10.1002/hon.2057
citation: Rummel MJ et al. Two years rituximab maintenance vs. observation after first-line treatment with bendamustine plus rituximab (B-R) in patients with mantle cell lymphoma: First results of a prospective, randomized, multicenter phase II study (a subgroup study of the StiL NHL7-2008 MAINTAIN trial). DOI: 10.1200/JCO.2016.34.15_suppl.7503 Journal of Clinical Oncology 34, no. 15_suppl (May 2016) 7503-7503.
citation: Rummel MJ, et al. Four Versus Two Years of Rituximab Maintenance (R-maintenance) Following Bendamustine Plus Rituximab (B-R): Initial Results of a Prospective, Randomized Multicenter Phase 3 Study in First-Line Follicular Lymphoma (the StiL NHL7-2008 MAINTAIN study). Blood (2017) 130 (Supplement 1): 483.
citation: Rummel MJ et al. Two years rituximab maintenance vs. observation after first line treatment with bendamustine plus rituximab (B-R) in patients with marginal zone lymphoma (MZL): Results of a prospective, randomized, multicenter phase 2 study (the StiL NHL7-2008 MAINTAIN trial). DOI: 10.1200/JCO.2018.36.15_suppl.7515 Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 7515-7515
citation: Rummel MJ et al. Two years Rituximab maintenance vs. observation after first line treatment with Bendamustine plus Rituximab in patients with Marginal Zone Lymphoma (MZL): results from the StiL NHL7-2008 MAINTAIN trial Results of a prospective, randomized, multicentre phase 2 study (a subgroup study of the StiL NHL7-2008 MAINTAIN trial).
citation: Rummel MJ et al. Two Years Rituximab Maintenance Vs. Observation after First Line Treatment with Bendamustine Plus Rituximab (B-R) in Patients with Waldenström's Macroglobulinemia (MW): Results of a Prospective, Randomized, Multicenter Phase 3 Study (the StiL NHL7-2008 MAINTAIN trial). Blood (2019) 134 (Supplement_1): 343. https://doi.org/10.1182/blood-2019-121909