Rituximab in Treating Patients With Follicular Non-Hodgkin's Lymphoma

NCT ID: NCT00227695

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-08
• Study Completion Date: 2017-12-19

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving rituximab over a short period of time is more effective than giving it over a long period of time in treating follicular non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab to see how well it works when given over a short period of time compared to when given over a long period of time in treating patients with follicular non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of induction therapy with rituximab followed by short- vs long-term maintenance therapy with rituximab, in terms of event-free survival, in patients with follicular non-Hodgkin's lymphoma.

Secondary

• Compare the safety of these regimens in these patients.
• Compare the pharmaeconomical aspects of these regimens in these patients.
• Compare the evolution of immunologic competence in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

• Induction therapy: Patients receive rituximab IV weekly in weeks 1-4 and undergo restaging between weeks 11-13. Patients with stable disease or progressive disease are taken off study. Patients achieving partial or complete response are stratified according to prior treatment status (untreated* vs treated with or without anti-CD20 therapy), presence of bulky disease** at study entry (yes vs no), and participating center. Patients are then randomized to 1 of 2 maintenance treatment arms.

NOTE: *Patients treated with radiotherapy only are considered as therapy-naïve.

NOTE: **Defined as a mass or lymph node conglomerate ≥ 5 cm diameter.

• Maintenance therapy: Patients start maintenance therapy within 7 days of randomization.

• Arm I: Patients receive rituximab IV every 2 months for 4 treatments.
• Arm II: Patients receive rituximab IV every 2 months for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until disease progression or relapse and then annually for up to 10 years after randomization.

PROJECTED ACCRUAL: A total of 270 patients will be accrued for this study within 3 years.

Conditions

Lymphoma

Study Design

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

Study Groups

Arm A: Rituximab every 2 months x4

Rituximab 375 mg/m2 every 2 months x4

Group Type: ACTIVE_COMPARATOR

rituximab

Intervention Type: BIOLOGICAL

comparing two maintenance schedules of Rituximab

Arm B: Rituximab (5 years)

Rituximab 375 mg/m2 every 2 months for 5 years or until PD, relapse or unacceptable toxicity

Group Type: ACTIVE_COMPARATOR

rituximab

Intervention Type: BIOLOGICAL

comparing two maintenance schedules of Rituximab

Interventions

rituximab

comparing two maintenance schedules of Rituximab

Intervention Type: BIOLOGICAL

Other Intervention Names

MABTHERA

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular lymphoma

• Grade 1, 2, 3a, or 3b disease by WHO staging system
• CD20-positive by immunohistochemistry
• Previously untreated disease OR meets 1 of the following criteria for response to prior treatment:

• Chemotherapy-resistant disease
• Relapsed or progressive disease
• Stable disease

• At least 12 weeks since prior systemic treatment
• At least 1 bidimensionally measurable lesion ≥ 11 mm by CT scan or MRI
• No transformation to high-grade lymphoma secondary to low-grade follicular lymphoma
• No prior or current CNS disease (i.e., CNS lymphoma or lymphomatous meningosis) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• Ejection fraction ≥ 50% by echocardiography or MUGA

Immunologic

• No acute or ongoing infection
• No HIV infection
• No active autoimmune disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of the study treatment
• No uncontrolled diabetes mellitus
• No other medical condition that would preclude study participation
• No other malignancy except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
• No other condition (e.g., geographic proximity) that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Radiotherapy
• Prior rituximab allowed

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• More than 4 weeks since prior regular administration of corticosteroids

• Dose equivalent to ≤ 20 mg/day prednisone allowed for conditions other than lymphoma or lymphoma-related symptoms
• No concurrent corticosteroids for prevention or treatment of side effects except acute life-threatening side effects

Radiotherapy

• Prior radiolabeled anti-CD20 therapy (administered alone or in combination with cytostatic drugs) allowed provided patient has achieved partial or complete response after the therapy

• At least 12 months since prior anti-CD20 therapy

Surgery

• Not specified

Other

• More than 30 days since prior systemic tumor therapy
• More than 30 days since prior participation in another clinical trial
• No other concurrent anticancer therapy

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

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Taverna, MD

Role: STUDY_CHAIR

Kantonsspital Münsterlingen

Michele Ghielmini, Prof.

Role: STUDY_CHAIR

IOSI - Ospedale San Giovanni, Bellinzona

Locations

Clinical Center - Institute of Hematology

São Paulo, , Brazil

Istituto Europeo di Oncologia IEO

Milan, , Italy

Clinical Center Skopje

Skopje, , North Macedonia

Clinical Center of Serbia

Belgrade, , Serbia

NOU - National Institute for Oncology

Bratislava, , Slovakia

Panorama Medical Centre

Cape Town, , South Africa

Sandton Oncology Centre

Johannesburg, , South Africa

Kantonspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

St. Claraspital AG

Basel, , Switzerland

Universitaetsspital Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Breitenbach Praxis Dr. Haberthür

Breitenbach, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital

Liestal, , Switzerland

Istituto Oncologico della Svizzera Italiana

Lugano, , Switzerland

Hôpital Pourtalès

Neuchâtel, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

SpitalSTS AG Simmental-Thun-Saanenland

Thun, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Brazil; Italy; North Macedonia; Serbia; Slovakia; South Africa; Switzerland

References

Taverna CJ, Baasi S, Hitz F, et al.: First results of long-term rituximab maintenance treatment in follicular lymphoma: safety analysis of the randomized phase III trial SAKK 35/03. [Abstract] J Clin Oncol 27 (Suppl 15): A-8534, 2009.

Reference Type: RESULT

First results of long term rituximab maintenance treatment in follicular lymphoma: safety analysis of the randomized phase III trial SAKK 35/03. F. Hitz, S. Bassi, C. Taverna, W. Mingrone, T. Pabst, L. Cevreska, A. Del Giglio, D.A. Vorobiof, M. Simcock, M. Ghielmini Haematologica (2009) 94: s2; abstract 0413

Reference Type: RESULT

First results of long term rituximab maintenance treatment in follicular lymphoma: safety analysis of the randomized phase III trial SAKK 35/03. C.J. Taverna, S. Bassi, F. Hitz, W. Mingrone, T. Pabst, L. Cevreska, A. del Giglio, D.A. Vorobiof, M. Simcock, M. Ghielmini J Clin Oncol (2009) 27: 15s supplement; abstract 8534

Reference Type: RESULT

Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: safety analysis of the randomized phase III trial SAKK 35/03. C. J. Taverna, S. Bassi, F. Hitz, W. Mingrone, T. Pabst, L. Cevreska, A. del Giglio, D.A. Vorobiof, M. Simcock, M. Ghielmini Blood (2010) 116: ASH Annual Meeting abstracts; abstract 1802

Reference Type: RESULT

Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. doi: 10.1200/JCO.2015.61.3968. Epub 2015 Dec 28.

Reference Type: RESULT

PMID: 26712227 (View on PubMed)

Other Identifiers

SWS-SAKK-35/03

Identifier Type: -

Identifier Source: secondary_id

EU-20520

Identifier Type: -

Identifier Source: secondary_id

CDR0000443594

Identifier Type: -

Identifier Source: secondary_id

SAKK 35/03

Identifier Type: -

Identifier Source: org_study_id