Significance of Duration of Maintenance Therapy With Rituximab in Non-Hodgkin Lymphomas

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.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

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 .

• BACKGROUNDRummel 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
• BACKGROUNDImmunochemotherapy 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
• BACKGROUNDRummel 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.
• BACKGROUNDRummel 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.
• BACKGROUNDRummel 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
• BACKGROUNDRummel 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).