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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00227695
First received: September 26, 2005
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: at 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: at 10 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: at 10 years ] [ Designated as safety issue: No ]
  • Adverse reactions during and after maintenance treatment [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 270
Study Start Date: June 2004
Estimated Study Completion Date: September 2017
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A: Rituximab every 2 months x4
Rituximab 375 mg/m2 every 2 months x4
Biological: rituximab
comparing two maintenance schedules of Rituximab
Other Name: MABTHERA
Active Comparator: Arm B: Rituximab (5 years)
Rituximab 375 mg/m2 every 2 months for 5 years or until PD, relapse or unacceptable toxicity
Biological: rituximab
comparing two maintenance schedules of Rituximab
Other Name: MABTHERA

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00227695

Locations
Brazil
Clinical Center - Institute of Hematology
Sao Paulo, Brazil
Italy
Istituto Europeo di Oncologia IEO
Milano, Italy, 20141
Macedonia, The Former Yugoslav Republic of
Clinical Center Skopje
Skopje, Macedonia, The Former Yugoslav Republic of, 1000
Serbia
Clinical Center of Serbia
Belgrade, Serbia, SCG-11000
Slovakia
NOU - National Institute for Oncology
Bratislava, Slovakia, 83310
South Africa
Panorama Medical Centre
Cape Town, South Africa, 7500
Sandton Oncology Centre
Johannesburg, South Africa, 2121
Switzerland
Kantonspital Aarau
Aarau, Switzerland, CH-5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Universitaetsspital Basel
Basel, Switzerland, CH-4031
St. Claraspital AG
Basel, Switzerland, CH-4016
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland, 6500
Inselspital Bern
Bern, Switzerland, 3010
Breitenbach Praxis Dr. Haberthür
Breitenbach, Switzerland, 4226
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital
Liestal, Switzerland, CH-4410
Istituto Oncologico della Svizzera Italiana
Lugano, Switzerland, CH-6900
Hôpital Pourtalès
Neuchâtel, Switzerland, 2002
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
SpitalSTS AG Simmental-Thun-Saanenland
Thun, Switzerland, 3600
City Hospital Triemli
Zurich, Switzerland, 8063
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Klinik Hirslanden
Zurich, Switzerland, CH-8032
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Christian Taverna, MD Kantonsspital Münsterlingen
Study Chair: Michele Ghielmini, Prof. IOSI - Ospedale San Giovanni, Bellinzona
  More Information

Publications:
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.
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

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00227695     History of Changes
Other Study ID Numbers: SAKK 35/03, SWS-SAKK-35/03, EU-20520, CDR0000443594
Study First Received: September 26, 2005
Last Updated: April 29, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
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

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 30, 2014