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

NCT ID: NCT00877214

Last Updated: 2024-08-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-01
• Study Completion Date: 2024-12-31

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.

Conditions

Follicular Lymphomas; Immunocytomas; Marginal Zone Lymphomas; Mantle-Cell Lymphomas; Lymphocytic Lymphoma; Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

Follicular Lymphomas: Rituximab 375 mg/m² for additional 2 years after 2 years of standard maintainance All other lymphomas: Rituximab 375 mg/m² for 2 years as maintainance. From 2014 only Morbus Waldenstroem: Rituximab 1.400 mg absolute s. c. injection

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Follicular Lymphomas: induction therapy with bendamustine + rituximab. If CR or PR: Maintenance therapy with rituximab every 2 months for 4 years Immunocytomas, marginal zone and mantle cell lymphomas: induction therapy with bendamustine + rituximab If CR or PR: Maintenance therapy with rituximab every 2 months for 2 years

Standard

Rituximab / Observation

Group Type: ACTIVE_COMPARATOR

Rituximab / observation

Intervention Type: DRUG

Follicular Lymphomas:induction therapy with bendamustine + rituximab If CR or PR: Maintenance therapy with rituximab every 2 months for 2 years (standard) Immunocytomas, marginal zone and mantle cell lymphomas: induction therapy with bendamustine + rituximab If CR or PR: observation (standard)

Interventions

Rituximab

Follicular Lymphomas: induction therapy with bendamustine + rituximab. If CR or PR: Maintenance therapy with rituximab every 2 months for 4 years Immunocytomas, marginal zone and mantle cell lymphomas: induction therapy with bendamustine + rituximab If CR or PR: Maintenance therapy with rituximab every 2 months for 2 years

Intervention Type: DRUG

Rituximab / observation

Follicular Lymphomas:induction therapy with bendamustine + rituximab If CR or PR: Maintenance therapy with rituximab every 2 months for 2 years (standard) Immunocytomas, marginal zone and mantle cell lymphomas: induction therapy with bendamustine + rituximab If CR or PR: observation (standard)

Intervention Type: DRUG

Other Intervention Names

Mabthera(R); Rituxan(R); Mabthera(R); Rituxan(R)

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

• 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 .

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sponsor GmbH

OTHER

Sponsor Role: collaborator

Jurgen Barth

OTHER

Sponsor Role: lead

Responsible Party

Jurgen Barth

Professor Mathias Rummel

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mathias Rummel, Dr

Role: PRINCIPAL_INVESTIGATOR

University of Giessen

Locations

StiL Head Office; Justus-Liebig-University

Giessen, , Germany

Countries

Germany

References

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

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

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).

Reference Type: BACKGROUND

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

Reference Type: BACKGROUND

Other Identifiers

NHL 7-2008

Identifier Type: -

Identifier Source: org_study_id