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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112931
• Other study ID #: CDR0000427312
• Secondary ID: CRUK-2004-001621
• Status: Completed
• Phase: Phase 3
• Start date: September 2004
• Est. completion date: September 14, 2023

Study information

• Verified date: May 2024
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 462
• Est. completion date: September 14, 2023
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• rituximab

Other:
• No treatment

Locations

Country	Name	City	State
Australia	Queen Elizabeth Hospital	Adelaide
Australia	Royal Adelaide Hospital	Adelaide
Australia	Ashford Cancer Centre	Black Forest
Australia	Boxhill Hospital	Box Hill
Australia	Royal Brisbane and Women's Hospital	Brisbane
Australia	Canberra Hospital	Canberra
Australia	Concord Repatriation General Hospital	Concord
Australia	Frankston Hospital	Frankston
Australia	Fremantle Hospital	Fremantle
Australia	Gosford Hospital	Gosford
Australia	Royal Hobart Hospital	Hobart
Australia	Nepean Hospital	Kingswood
Australia	Lismore Base Hospital	Lismore
Australia	Liverpool Hospital	Liverpool
Australia	Alfred Hospital	Melbourne
Australia	Austin Health	Melbourne
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	St Vincent's Hospital	Melbourne
Australia	Mater Misericordiae Hospital	Newcastle
Australia	Royal Perth Hospital	Perth
Australia	Royal North Shore Hospital	St Leonards
Australia	St Vincent's Hospital	Sydney
Australia	Westmead Hospital	Westmead
Australia	Murray Valley Private Hospital	Wodonga
Australia	Wollongong Hospital	Wollongong
Australia	Princess Alexandra Hospital	Woolloongabba
New Zealand	Auckland Hospital	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	North Shore Hospital	Westlake
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Monklands General Hospital	Airdrie	Scotland
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	Blackpool Victoria Hospital	Blackpool	England
United Kingdom	West Suffolk Hospital	Bury St. Edmunds	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	St. Helier Hospital	Carshalton	England
United Kingdom	Hairmyres Hospital	East Kilbride	Scotland
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Queen Elizabeth Hospital	Gateshead	England
United Kingdom	Medway Maritime Hospital	Gillingham	England
United Kingdom	Southern General Hospital	Glasgow	Scotland
United Kingdom	Hemel Hempstead General	Hemel Hempstead	England
United Kingdom	Hull Royal Infirmary	Hull	England
United Kingdom	Raigmore Hospital	Inverness	Scotland
United Kingdom	West Middlesex University Hospital	Isleworth	England
United Kingdom	Kettering General Hosptial	Kettering	England
United Kingdom	Kidderminster Hospital	Kidderminster	England
United Kingdom	Queen Elizabeth Hospital	King's Lynn	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Prince Charles Hospital	Merthyr Tydfil	Wales
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Royal Alexandra Hospital	Paisley	Scotland
United Kingdom	Rosemere Cancer Centre at Royal Preston Hospital	Preston	England
United Kingdom	Alexandra Healthcare NHS	Redditch	England
United Kingdom	Glan Clwyd Hospital	Rhyl	Wales
United Kingdom	Oldchurch Hospital	Romford	England
United Kingdom	Pembury Hospital	Royal Tunbridge Wells	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Staffordshire General Hospital	Stafford	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	South West Wales Cancer Institute	Swansea	Wales
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Royal Cornwall Hospital	Truro	England
United Kingdom	Weston General Hospital	Weston-super-Mare	England
United Kingdom	Wishaw General Hospital	Wishaw	Scotland
United Kingdom	Worcester Royal Hospital	Worcester	England

Sponsors (3)

Lead Sponsor	Collaborator
University College, London	Cancer Research UK, Roche Pharma AG

Countries where clinical trial is conducted

Australia,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time until initiation of therapy (chemotherapy or radiotherapy)		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	Frequency of clinical spontaneous remission		From randomisation until the initiation of chemotherapy in the watch and wait arm
Secondary	Cause specific survival		Time from randomisation to death from lymphoma or immediate therapy related toxicity
Secondary	Overall survival		Time from randomisation to death from any cause.
Secondary	Response rate at 25 months		Response at 25 months