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

May 13, 2019 updated by: Swiss Group for Clinical Cancer Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

270

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Sao Paulo, Brazil
        • Clinical Center - Institute of Hematology
  • Italy
      • Milano, Italy, 20141
        • Istituto Europeo di Oncologia IEO
  • North Macedonia
      • Skopje, North Macedonia, 1000
        • Clinical Center Skopje
  • Serbia
      • Belgrade, Serbia, SCG-11000
        • Clinical Center of Serbia
  • Slovakia
      • Bratislava, Slovakia, 83310
        • NOU - National Institute for Oncology
  • South Africa
      • Cape Town, South Africa, 7500
        • Panorama Medical Centre
      • Johannesburg, South Africa, 2121
        • Sandton Oncology Centre
  • Switzerland
      • Aarau, Switzerland, CH-5001
        • Kantonspital Aarau
      • Baden, Switzerland, CH-5404
        • Kantonsspital Baden
      • Basel, Switzerland, CH-4016
        • St. Claraspital AG
      • Basel, Switzerland, CH-4031
        • Universitaetsspital Basel
      • Bellinzona, Switzerland, 6500
        • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
      • Bern, Switzerland, 3010
        • Inselspital Bern
      • Breitenbach, Switzerland, 4226
        • Breitenbach Praxis Dr. Haberthür
      • Bruderholz, Switzerland, CH-4101
        • Kantonsspital Bruderholz
      • Chur, Switzerland, CH-7000
        • Kantonsspital Graubuenden
      • Geneva, Switzerland, CH-1211
        • Hôpital Cantonal Universitaire de Genève
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • Liestal, Switzerland, CH-4410
        • Kantonsspital
      • Lugano, Switzerland, CH-6900
        • Istituto Oncologico della Svizzera Italiana
      • Neuchâtel, Switzerland, 2002
        • Hôpital Pourtalès
      • St. Gallen, Switzerland, CH-9007
        • Kantonsspital - St. Gallen
      • Thun, Switzerland, 3600
        • SpitalSTS AG Simmental-Thun-Saanenland
      • Zurich, Switzerland, CH-8091
        • Universitaetsspital Zuerich
      • Zurich, Switzerland, CH-8032
        • Klinik Hirslanden
      • Zurich, Switzerland, 8063
        • City Hospital Triemli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • MABTHERA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Event-free survival
Time Frame: at 10 years
at 10 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: at 10 years
at 10 years
Progression-free survival
Time Frame: at 10 years
at 10 years
Adverse reactions during and after maintenance treatment
Time Frame: 10 years
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swiss Group for Clinical Cancer Research

Investigators

  • Study Chair: Christian Taverna, MD, Kantonsspital Münsterlingen
  • Study Chair: Michele Ghielmini, Prof., IOSI - Ospedale San Giovanni, Bellinzona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 8, 2004

Primary Completion (Actual)

May 3, 2013

Study Completion (Actual)

December 19, 2017

Study Registration Dates

First Submitted

September 26, 2005

First Submitted That Met QC Criteria

September 26, 2005

First Posted (Estimate)

September 28, 2005

Study Record Updates

Last Update Posted (Actual)

May 15, 2019

Last Update Submitted That Met QC Criteria

May 13, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAKK 35/03
  • SWS-SAKK-35/03
  • EU-20520
  • CDR0000443594

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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