Clinical trial NCT00227695: Rituximab in Treating Patients With Follicular Non-Hodgkin's Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2005-09-28
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Event-free survival
timeFrame: at 10 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: at 10 years
measure: Overall survival
timeFrame: at 10 years
measure: Adverse reactions during and after maintenance treatment
timeFrame: 10 years
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Clinical Center - Institute of Hematology
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IEO
city: Skopje
country: North Macedonia
facility: Clinical Center Skopje
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Bratislava
country: Slovakia
facility: NOU - National Institute for Oncology
city: Cape Town
country: South Africa
facility: Panorama Medical Centre
city: Johannesburg
country: South Africa
facility: Sandton Oncology Centre
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: St. Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Breitenbach
country: Switzerland
facility: Breitenbach Praxis Dr. Haberthür
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Liestal
country: Switzerland
facility: Kantonsspital
city: Lugano
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: Neuchâtel
country: Switzerland
facility: Hôpital Pourtalès
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: SpitalSTS AG Simmental-Thun-Saanenland
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: Klinik Hirslanden
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Kantonsspital Münsterlingen
name: Christian Taverna, MD
role: STUDY_CHAIR
affiliation: IOSI - Ospedale San Giovanni, Bellinzona
name: Michele Ghielmini, Prof.
role: STUDY_CHAIR
References:
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.
citation: 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
citation: 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
citation: 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
citation: 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.