Clinical trial NCT00112931: Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma
Official title: An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy in Patients With Advanced Stage, Asymptomatic, Non-Bulky Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: 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
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II 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
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: Roche Pharma AG
First posted: 2005-06-03
Enrollment: 462
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Time until initiation of therapy (chemotherapy or radiotherapy)
timeFrame: 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 outcomes:
measure: Frequency of clinical spontaneous remission
timeFrame: From randomisation until the initiation of chemotherapy in the watch and wait arm
measure: Cause specific survival
timeFrame: Time from randomisation to death from lymphoma or immediate therapy related toxicity
measure: Overall survival
timeFrame: Time from randomisation to death from any cause.
measure: Response rate at 25 months
timeFrame: Response at 25 months
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Queen Elizabeth Hospital
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Black Forest
country: Australia
facility: Ashford Cancer Centre
city: Box Hill
country: Australia
facility: Boxhill Hospital
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Canberra
country: Australia
facility: Canberra Hospital
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Frankston
country: Australia
facility: Frankston Hospital
city: Fremantle
country: Australia
facility: Fremantle Hospital
city: Gosford
country: Australia
facility: Gosford Hospital
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Kingswood
country: Australia
facility: Nepean Hospital
city: Lismore
country: Australia
facility: Lismore Base Hospital
city: Liverpool
country: Australia
facility: Liverpool Hospital
city: Melbourne
country: Australia
facility: Alfred Hospital
city: Melbourne
country: Australia
facility: Austin Health
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Melbourne
country: Australia
facility: St Vincent's Hospital
city: Newcastle
country: Australia
facility: Mater Misericordiae Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
city: Sydney
country: Australia
facility: St Vincent's Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Wodonga
country: Australia
facility: Murray Valley Private Hospital
city: Wollongong
country: Australia
facility: Wollongong Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Westlake
country: New Zealand
facility: North Shore Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Bury St. Edmunds
country: United Kingdom
facility: West Suffolk Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Carshalton
country: United Kingdom
facility: St. Helier Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
state: England
city: Hemel Hempstead
country: United Kingdom
facility: Hemel Hempstead General
state: England
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: England
city: Isleworth
country: United Kingdom
facility: West Middlesex University Hospital
state: England
city: Kettering
country: United Kingdom
facility: Kettering General Hosptial
state: England
city: Kidderminster
country: United Kingdom
facility: Kidderminster Hospital
state: England
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Redditch
country: United Kingdom
facility: Alexandra Healthcare NHS
state: England
city: Romford
country: United Kingdom
facility: Oldchurch Hospital
state: England
city: Royal Tunbridge Wells
country: United Kingdom
facility: Pembury Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Weston-super-Mare
country: United Kingdom
facility: Weston General Hospital
state: England
city: Worcester
country: United Kingdom
facility: Worcester Royal Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Airdrie
country: United Kingdom
facility: Monklands General Hospital
state: Scotland
city: East Kilbride
country: United Kingdom
facility: Hairmyres Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Southern General Hospital
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Paisley
country: United Kingdom
facility: Royal Alexandra Hospital
state: Scotland
city: Wishaw
country: United Kingdom
facility: Wishaw General Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Merthyr Tydfil
country: United Kingdom
facility: Prince Charles Hospital
state: Wales
city: Rhyl
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: South West Wales Cancer Institute
state: Wales
Study officials:
affiliation: Mount Vernon Cancer Centre at Mount Vernon Hospital
name: Kirit Ardeshna
role: STUDY_CHAIR
References:
citation: 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.