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

Lymphoma Clinical Trial

Official title:

Comparing Two Schedules of Rituximab Maintenance in Rituximab-Responding Patients With Untreated, Chemotherapy Resistant or Relapsed Follicular Lymphoma: A Randomized Phase III Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00227695
• Other study ID #: SAKK 35/03
• Secondary ID: SWS-SAKK-35/03EU
• Status: Completed
• Phase: Phase 3
• Start date: June 8, 2004
• Est. completion date: December 19, 2017

Study information

• Verified date: May 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: December 19, 2017
• Est. primary completion date: May 3, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• rituximab
comparing two maintenance schedules of Rituximab

Locations

Country	Name	City	State
Brazil	Clinical Center - Institute of Hematology	Sao Paulo
Italy	Istituto Europeo di Oncologia IEO	Milano
North Macedonia	Clinical Center Skopje	Skopje
Serbia	Clinical Center of Serbia	Belgrade
Slovakia	NOU - National Institute for Oncology	Bratislava
South Africa	Panorama Medical Centre	Cape Town
South Africa	Sandton Oncology Centre	Johannesburg
Switzerland	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	St. Gallen
Switzerland	SpitalSTS AG Simmental-Thun-Saanenland	Thun
Switzerland	City Hospital Triemli	Zurich
Switzerland	Klinik Hirslanden	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

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

References & Publications (5)

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,

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

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,

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 — View Citation

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival		at 10 years
Secondary	Progression-free survival		at 10 years
Secondary	Overall survival		at 10 years
Secondary	Adverse reactions during and after maintenance treatment		10 years