A Phase IIIb, randomized study comparing maintenance therapy with subcutaneous rituximab continued until progression and observation in patients with relapsed or refractory, indolent non-Hodgkin’s lymphoma who completed and responded to rituximab-based immunochemotherapy induction and initial 2-year rituximab maintenance therapy administered subcutaneously.

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2010-023407-95-AT
• Date of registration: 08/08/2011
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Phase IIIb, randomized study comparing maintenance therapy with subcutaneous rituximab continued until progression and observation in patients with relapsed or refractory, indolent non-Hodgkin’s lymphoma who completed and responded to rituximab-based immunochemotherapy induction and initial 2-year rituximab maintenance therapy administered subcutaneously.
• Scientific title: A randomized study comparing maintenance therapy with subcutaneous rituximab continued until progression with observation only in patients with relapsed or refractory, indolent non-Hodgkin’s lymphoma who completed and responded to rituximab-based immunochemotherapy induction and initial 2-year rituximab maintenance therapy administered subcutaneously.
• Date of first enrolment: 21/09/2011
• Target sample size: 700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023407-95
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: observation arm (no treatment); Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Albania, Argentina, Austria, Brazil, Bulgaria, Canada, Colombia, Ecuador, Egypt, France, Germany, Greece, Hungary, Italy, Lithuania, Norway, Romania, Russian Federation, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Age = 18 years.
• Histologically confirmed, CD20+ follicular NHL Grade 1, 2 or 3a, or other CD20+ indolent NHL (Waldenström’s macroglobulinemia or lymphoplasmacytic lymphoma, marginal zone lymphoma) according to the WHO classification system.
• Patients must have received, and must have relapsed or been refractory to, one or more lines of adequate therapy prior to enrolment, including at least one line consisting of immunotherapy and/or chemotherapy and/or radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status = 2.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 350

Exclusion criteria:
• Transformation to high-grade lymphoma.
• Patients with aggressive lymphoma (e.g. mantle cell lymphoma).
• Presence or history of central nervous system (CNS) lymphomatous disease (e.g., CNS lymphoma or lymphomatous meningitis).
• Other malignancy within 5 years prior to enrolment, with the following exceptions (as long as curatively treated): carcinoma in situ of the cervix, squamous cell carcinoma of the skin, or basal cell skin cancer. Cervical carcinoma stage 1B or less, breast cancer in situ, or localized prostate cancer stage T1c or less may be considered, provided that the patient was treated with curative intent and has been relapse- and metastasis-free for at least 2 years prior to enrolment.
• Inadequate hepatic or renal function prior to the first rituximab induction dose.
• Known human immunodeficiency virus (HIV) infection.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with relapsed or refractory CD20+ follicular non-Hodgkin’s lymphoma (NHL) Grade 1, 2 or 3a, or other CD20+ indolent NHL (Waldenström’s macroglobulinemia or lymphoplasmacytic lymphoma, marginal zone lymphoma), according to the WHO classification system.
MedDRA version: 20.0 Level: LLT Classification code 10067070 Term: Follicular B-cell non-Hodgkin's lymphoma System Organ Class: 100000013103

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: MabThera®

Pharmaceutical Form: Solution for injection
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: Ro 045-2294
Other descriptive name: rituximab/rHuPH20 SC
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-

Trade Name: MabThera®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: R00452294
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: To evaluate the efficacy of a subcutaneous (SC) formulation of rituximab in term of progression-free survival after randomization (PFSrand) to either prolonged rituximab maintenance until progression (Maintenance II) or observation in patients with relapsed or refractory, indolent non-Hodgkin’s lymphoma who responded to Induction and initial 2 years maintenance therapy (Maintenance I).

Timepoint(s) of evaluation of this end point: Day 1 every 8 weeks [56 ± 7 days] until PD

Primary end point(s): The primary efficacy endpoint of the study is PFSrand. It is defined as the time from day of randomization to the first documented disease progression or death, whichever occurs first.

Secondary Objective: To evaluate the efficacy and safety of SC rituximab during Induction, initial 2-year maintenance (Maintenance I) and randomized treatment period (Maintenance II). Efficacy will be evaluated in terms of Event-Free Survival (EFS), Time to Next Lymphoma Treatment (TNLT), Overall survival measured from the first Induction dose of rituximab (OSregist) and from the time of randomization to Maintenance II (OSrand), Overall Response Rate (ORR), Partial Response (PR) to Complete Response (CR) conversion rate at the end of Maintenance I, and PFS measured from the first Induction dose of rituximab (PFSregist). Safety assessments will include frequency of adverse events (AEs), serious adverse events (SAEs), and infusion/administration-related reactions (IRRs/ARRs) and immunoglobulin (Ig) quantification.

Secondary Outcome(s)

Secondary end point(s): Progression free survival (PFS) measured from the day of first rituximab Induction dose (PFSregist), Event-free survival (EFS), Time to next lymphoma treatment (TNLT), Overall survival measured from day of first rituximab Induction dose (OSregist) and from randomization (OSrand), Overall Response Rate (ORR) at the end of the Induction Phase and PR to CR conversion rate at the end of Maintenance I.

Timepoint(s) of evaluation of this end point: Week 24 (cycle 8)

Secondary ID(s)

2010-023407-95-GB

MO25455

NCT01461928

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd