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

NCT ID: NCT00112931

Last Updated: 2024-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

462 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-09-30

Study Completion Date

2023-09-14

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Watch and Wait

Watch and Wait - no treatment

Group Type ACTIVE_COMPARATOR

No treatment

Intervention Type OTHER

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

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

Interventions

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rituximab

Intervention Type BIOLOGICAL

No treatment

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

Roche Pharma AG

INDUSTRY

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kirit Ardeshna

Role: STUDY_CHAIR

Mount Vernon Cancer Centre at Mount Vernon Hospital

Locations

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Queen Elizabeth Hospital

Adelaide, , Australia

Site Status

Royal Adelaide Hospital

Adelaide, , Australia

Site Status

Ashford Cancer Centre

Black Forest, , Australia

Site Status

Boxhill Hospital

Box Hill, , Australia

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Royal Brisbane and Women's Hospital

Brisbane, , Australia

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Canberra Hospital

Canberra, , Australia

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Concord Repatriation General Hospital

Concord, , Australia

Site Status

Frankston Hospital

Frankston, , Australia

Site Status

Fremantle Hospital

Fremantle, , Australia

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Gosford Hospital

Gosford, , Australia

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Royal Hobart Hospital

Hobart, , Australia

Site Status

Nepean Hospital

Kingswood, , Australia

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Lismore Base Hospital

Lismore, , Australia

Site Status

Liverpool Hospital

Liverpool, , Australia

Site Status

Alfred Hospital

Melbourne, , Australia

Site Status

Austin Health

Melbourne, , Australia

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Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status

St Vincent's Hospital

Melbourne, , Australia

Site Status

Mater Misericordiae Hospital

Newcastle, , Australia

Site Status

Royal Perth Hospital

Perth, , Australia

Site Status

Royal North Shore Hospital

St Leonards, , Australia

Site Status

St Vincent's Hospital

Sydney, , Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

Murray Valley Private Hospital

Wodonga, , Australia

Site Status

Wollongong Hospital

Wollongong, , Australia

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Princess Alexandra Hospital

Woolloongabba, , Australia

Site Status

Auckland Hospital

Auckland, , New Zealand

Site Status

Middlemore Hospital

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

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North Shore Hospital

Westlake, , New Zealand

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Birmingham Heartlands Hospital

Birmingham, England, United Kingdom

Site Status

Blackpool Victoria Hospital

Blackpool, England, United Kingdom

Site Status

West Suffolk Hospital

Bury St Edmunds, England, United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

Site Status

St. Helier Hospital

Carshalton, England, United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

Site Status

Queen Elizabeth Hospital

Gateshead, England, United Kingdom

Site Status

Medway Maritime Hospital

Gillingham, England, United Kingdom

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Hemel Hempstead General

Hemel Hempstead, England, United Kingdom

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Hull Royal Infirmary

Hull, England, United Kingdom

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West Middlesex University Hospital

Isleworth, England, United Kingdom

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Kettering General Hosptial

Kettering, England, United Kingdom

Site Status

Kidderminster Hospital

Kidderminster, England, United Kingdom

Site Status

Queen Elizabeth Hospital

Kings Lynn, England, United Kingdom

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Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

St. George's Hospital

London, England, United Kingdom

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Maidstone Hospital

Maidstone, England, United Kingdom

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Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Newcastle upon Tyne, England, United Kingdom

Site Status

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Site Status

Rosemere Cancer Centre at Royal Preston Hospital

Preston, England, United Kingdom

Site Status

Alexandra Healthcare NHS

Redditch, England, United Kingdom

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Oldchurch Hospital

Romford, England, United Kingdom

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Pembury Hospital

Royal Tunbridge Wells, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Staffordshire General Hospital

Stafford, England, United Kingdom

Site Status

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status

Torbay Hospital

Torquay, England, United Kingdom

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Royal Cornwall Hospital

Truro, England, United Kingdom

Site Status

Weston General Hospital

Weston-super-Mare, England, United Kingdom

Site Status

Worcester Royal Hospital

Worcester, England, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Site Status

Monklands General Hospital

Airdrie, Scotland, United Kingdom

Site Status

Hairmyres Hospital

East Kilbride, Scotland, United Kingdom

Site Status

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, United Kingdom

Site Status

Southern General Hospital

Glasgow, Scotland, United Kingdom

Site Status

Raigmore Hospital

Inverness, Scotland, United Kingdom

Site Status

Royal Alexandra Hospital

Paisley, Scotland, United Kingdom

Site Status

Wishaw General Hospital

Wishaw, Scotland, United Kingdom

Site Status

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, United Kingdom

Site Status

Prince Charles Hospital

Merthyr Tydfil, Wales, United Kingdom

Site Status

Glan Clwyd Hospital

Rhyl, Wales, United Kingdom

Site Status

South West Wales Cancer Institute

Swansea, Wales, United Kingdom

Site Status

Countries

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Australia New Zealand United Kingdom

References

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Northend M, Wilson W, Ediriwickrema K, Clifton-Hadley L, Qian W, Rana Z, Martin TL, Townsend W, Young M, Miall F, Cunningham D, Walewski J, Ferhanoglu B, Linton K, Johnston A, Seymour JF, Linch DC, Ardeshna KM. Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial. Lancet Haematol. 2025 May;12(5):e335-e345. doi: 10.1016/S2352-3026(25)00034-1.

Reference Type DERIVED
PMID: 40306831 (View on PubMed)

Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. doi: 10.1016/S1470-2045(14)70027-0. Epub 2014 Mar 4.

Reference Type DERIVED
PMID: 24602760 (View on PubMed)

Other Identifiers

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CRUK-2004-001621-16

Identifier Type: -

Identifier Source: secondary_id

EU-20509

Identifier Type: -

Identifier Source: secondary_id

ROCHE-CRUK-001621-16

Identifier Type: -

Identifier Source: secondary_id

CDR0000427312

Identifier Type: -

Identifier Source: org_study_id

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