Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

May 9, 2023 updated by: University College, London

An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy in Patients With Advanced Stage, Asymptomatic, Non-Bulky Follicular Lymphoma

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 rituximab is more effective than observation in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab to see how well it works compared to observation in treating patients with newly diagnosed stage II, stage III, or stage IV follicular non-Hodgkin's lymphoma with no symptoms.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare time to initiation of systemic chemotherapy or radiotherapy in patients with newly diagnosed, previously untreated, asymptomatic stage II-IV non-bulky follicular non-Hodgkin's lymphoma treated with rituximab vs observation only.

Secondary

  • Compare the frequency of clinical spontaneous remission in patients treated with these regimens.
  • Compare overall and cause-specific survival of patients treated with these regimens.
  • Determine the effect of rituximab on complete and partial response in patients treated with subsequent systemic chemotherapy.
  • Compare quality of life, in terms of functional well-being and anxiety and depression, of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease grade (1 vs 2 vs 3a), disease stage (II vs III vs IV), and age. Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients undergo observation only until disease progression.
  • Arm II: Patients receive induction rituximab IV on day 1. Treatment repeats weekly for up to 4 weeks.
  • Arm III: Patients receive induction rituximab as in arm II. Patients then receive maintenance rituximab IV once on day 1 of weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100.

In all arms, treatment continues in the absence of unacceptable toxicity or disease progression requiring systemic chemotherapy* or radiotherapy.

NOTE: *Rituximab administration in arm I is considered initiation of systemic chemotherapy

Quality of life is assessed at baseline (before and after randomization), every 2 months for 2 years, and then every 6 months for 2 years.

Patients are followed every 2 months for 2 years and then every 3 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 600 patients (200 per treatment arm) will be accrued for this study within 3 years.

Study Type

Interventional

Enrollment (Anticipated)

600

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

  • Australia
      • Adelaide, Australia
        • Royal Adelaide Hospital
      • Adelaide, Australia
        • Queen Elizabeth Hospital
      • Black Forest, Australia
        • Ashford Cancer Centre
      • Box Hill, Australia
        • Boxhill Hospital
      • Brisbane, Australia
        • Royal Brisbane and Women's Hospital
      • Canberra, Australia
        • Canberra Hospital
      • Concord, Australia
        • Concord Repatriation General Hospital
      • Frankston, Australia
        • Frankston Hospital
      • Fremantle, Australia
        • Fremantle Hospital
      • Gosford, Australia
        • Gosford Hospital
      • Hobart, Australia
        • Royal Hobart Hospital
      • Kingswood, Australia
        • Nepean Hospital
      • Lismore, Australia
        • Lismore Base Hospital
      • Liverpool, Australia
        • Liverpool Hospital
      • Melbourne, Australia
        • Alfred Hospital
      • Melbourne, Australia
        • Austin Health
      • Melbourne, Australia
        • St Vincent's hospital
      • Melbourne, Australia
        • Peter MacCallum Cancer Centre
      • Newcastle, Australia
        • Mater Misericordiae Hospital
      • Perth, Australia
        • Royal Perth Hospital
      • St Leonards, Australia
        • Royal North Shore Hospital
      • Sydney, Australia
        • St Vincent's hospital
      • Westmead, Australia
        • Westmead Hospital
      • Wodonga, Australia
        • Murray Valley Private Hospital
      • Wollongong, Australia
        • Wollongong Hospital
      • Woolloongabba, Australia
        • Princess Alexandra Hospital
  • New Zealand
      • Auckland, New Zealand
        • Middlemore Hospital
      • Auckland, New Zealand
        • Auckland Hospital
      • Christchurch, New Zealand
        • Christchurch Hospital
      • Westlake, New Zealand
        • North Shore Hospital
  • United Kingdom
    • England
      • Birmingham, England, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital
      • Blackpool, England, United Kingdom, FY3 8NR
        • Blackpool Victoria Hospital
      • Bury St. Edmunds, England, United Kingdom, IP33 2QZ
        • West Suffolk Hospital
      • Canterbury, England, United Kingdom, CT1 3NG
        • Kent and Canterbury Hospital
      • Carshalton, England, United Kingdom, SM5 1AA
        • St. Helier Hospital
      • Exeter, England, United Kingdom, EX2 5DW
        • Royal Devon and Exeter Hospital
      • Gateshead, England, United Kingdom, NE9 6SX
        • Queen Elizabeth Hospital
      • Gillingham, England, United Kingdom, ME7 5NY
        • Medway Maritime Hospital
      • Hemel Hempstead, England, United Kingdom, HP2 4AD
        • Hemel Hempstead General
      • Hull, England, United Kingdom, HU3 2KZ
        • Hull Royal Infirmary
      • Isleworth, England, United Kingdom, TW7 6AF
        • West Middlesex University Hospital
      • Kettering, England, United Kingdom, NNI6 8UZ
        • Kettering General Hosptial
      • Kidderminster, England, United Kingdom, DY11 6RJ
        • Kidderminster Hospital
      • King's Lynn, England, United Kingdom, PE30 4ET
        • Queen Elizabeth Hospital
      • Leicester, England, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • London, England, United Kingdom, SW17 0QT
        • St. George's Hospital
      • Maidstone, England, United Kingdom, ME16 9QQ
        • Maidstone Hospital
      • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
        • Sir James Spence Institute of Child Health at Royal Victoria Infirmary
      • Northwood, England, United Kingdom, HA6 2RN
        • Mount Vernon Cancer Centre at Mount Vernon Hospital
      • Preston, England, United Kingdom, PR2 9HT
        • Rosemere Cancer Centre at Royal Preston Hospital
      • Redditch, England, United Kingdom, B98 7UB
        • Alexandra Healthcare NHS
      • Romford, England, United Kingdom, RM7 OBE
        • Oldchurch Hospital
      • Royal Tunbridge Wells, England, United Kingdom, TN2 4QJ
        • Pembury Hospital
      • Southampton, England, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Stafford, England, United Kingdom, ST16 3SA
        • Staffordshire General Hospital
      • Sutton, England, United Kingdom, SM2 5PT
        • Royal Marsden - Surrey
      • Torquay, England, United Kingdom, TQ2 7AA
        • Torbay Hospital
      • Truro, England, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospital
      • Weston-super-Mare, England, United Kingdom, BS23 4TQ
        • Weston General Hospital
      • Worcester, England, United Kingdom, WR5 1DD
        • Worcester Royal Hospital
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB25 2ZN
        • Aberdeen Royal Infirmary
      • Airdrie, Scotland, United Kingdom, ML6 0JF
        • Monklands General Hospital
      • East Kilbride, Scotland, United Kingdom, G75 8RG
        • Hairmyres Hospital
      • Edinburgh, Scotland, United Kingdom, EH4 2XU
        • Edinburgh Cancer Centre at Western General Hospital
      • Glasgow, Scotland, United Kingdom, G51 4TF
        • Southern General Hospital
      • Inverness, Scotland, United Kingdom, 1V2 3UJ
        • Raigmore Hospital
      • Paisley, Scotland, United Kingdom
        • Royal Alexandra Hospital
      • Wishaw, Scotland, United Kingdom, ML2 0DP
        • Wishaw General Hospital
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 2TL
        • Velindre Cancer Center at Velindre Hospital
      • Merthyr Tydfil, Wales, United Kingdom, CF47 9DT
        • Prince Charles Hospital
      • Rhyl, Wales, United Kingdom, LL 18 5UJ
        • Glan Clwyd Hospital
      • Swansea, Wales, United Kingdom, SA2 8QA
        • South West Wales Cancer Institute

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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed follicular non-Hodgkin's lymphoma

    • Diagnosed within the past 3 months
    • Grade 1, 2, or 3a disease
    • Stage II-IV disease
    • No evidence of histological transformation
  • Bidimensionally measurable disease by clinical examination or radiography
  • Asymptomatic disease without B symptoms or severe pruritus

  • Low tumor burden, defined by all of the following criteria:

    • Lactic dehydrogenase normal
    • Largest nodal or extranodal mass < 7 cm
    • No more than 3 nodal sites with a diameter > 3 cm

    • No clinically detectable significant serous effusion by chest x-ray

      • Clinically non-evident small effusion on CT scan is not considered significant
    • Spleen enlargement ≤ 16 cm by CT scan
  • Circulating tumor cells < 5,000/mm^3
  • No organ compression (i.e., ureteric obstruction)

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 10 g/dL

Hepatic

  • AST and ALT normal
  • Alkaline phosphatase normal
  • Bilirubin normal

Renal

  • Creatinine < 2 times upper limit of normal (unless due to lymphoma)

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 12 months after completion of rituximab
  • No known HIV positivity
  • No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No critical organ failure
  • No other immediate life-threatening disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No prior therapy for lymphoma

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: Watch and Wait
Watch and Wait - no treatment
Other: No treatment
Experimental: Arm C Rituximab 4 and Rixuximab Maintenance
4 infusions - 375mg/m2 every 2 months. A single dose of rituximab (375mg/m2 will then be given at 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92 and 100 weeks
Biological: rituximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time until initiation of therapy (chemotherapy or radiotherapy)
Time Frame: Time from randomisation until the first day systemic chemotherapy or radiotherapy is given. If rituximab is given to patients in the watch and wait arm this will be considered as initiation of chemotherapy.
Time from randomisation until the first day systemic chemotherapy or radiotherapy is given. If rituximab is given to patients in the watch and wait arm this will be considered as initiation of chemotherapy.

Secondary Outcome Measures

Outcome Measure
Time Frame
Frequency of clinical spontaneous remission
Time Frame: From randomisation until the initiation of chemotherapy in the watch and wait arm
From randomisation until the initiation of chemotherapy in the watch and wait arm
Cause specific survival
Time Frame: Time from randomisation to death from lymphoma or immediate therapy related toxicity
Time from randomisation to death from lymphoma or immediate therapy related toxicity
Overall survival
Time Frame: Time from randomisation to death from any cause.
Time from randomisation to death from any cause.
Response rate at 25 months
Time Frame: Response at 25 months
Response at 25 months

Collaborators and Investigators

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

Sponsor

University College, London

Collaborators

Roche Pharma AG
Cancer Research UK

Investigators

  • Study Chair: Kirit Ardeshna, Mount Vernon Cancer Centre at Mount Vernon Hospital

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

September 1, 2004

Primary Completion (Actual)

March 1, 2014

Study Completion (Anticipated)

May 1, 2023

Study Registration Dates

First Submitted

June 2, 2005

First Submitted That Met QC Criteria

June 2, 2005

First Posted (Estimate)

June 3, 2005

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000427312
  • CRUK-2004-001621-16
  • EU-20509
  • ROCHE-CRUK-001621-16

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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