Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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
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Compare the frequency of clinical spontaneous remission in patients treated with these regimens.
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Compare overall and cause-specific survival of patients treated with these regimens.
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Determine the effect of rituximab on complete and partial response in patients treated with subsequent systemic chemotherapy.
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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.
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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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Frequency of clinical spontaneous remission [From randomisation until the initiation of chemotherapy in the watch and wait arm]
- Cause specific survival [Time from randomisation to death from lymphoma or immediate therapy related toxicity]
- Overall survival [Time from randomisation to death from any cause.]
- Response rate at 25 months [Response at 25 months]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically confirmed follicular non-Hodgkin's lymphoma
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Diagnosed within the past 3 months
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Grade 1, 2, or 3a disease
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Stage II-IV disease
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No evidence of histological transformation
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Bidimensionally measurable disease by clinical examination or radiography
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Asymptomatic disease without B symptoms or severe pruritus
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Low tumor burden, defined by all of the following criteria:
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Lactic dehydrogenase normal
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Largest nodal or extranodal mass < 7 cm
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No more than 3 nodal sites with a diameter > 3 cm
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No clinically detectable significant serous effusion by chest x-ray
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Clinically non-evident small effusion on CT scan is not considered significant
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Spleen enlargement ≤ 16 cm by CT scan
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Circulating tumor cells < 5,000/mm^3
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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
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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
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Not pregnant or nursing
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Fertile patients must use effective contraception during and for 12 months after completion of rituximab
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No known HIV positivity
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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
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No critical organ failure
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Queen Elizabeth Hospital | Adelaide | Australia | ||
| 2 | Royal Adelaide Hospital | Adelaide | Australia | ||
| 3 | Ashford Cancer Centre | Black Forest | Australia | ||
| 4 | Boxhill Hospital | Box Hill | Australia | ||
| 5 | Royal Brisbane and Women's Hospital | Brisbane | Australia | ||
| 6 | Canberra Hospital | Canberra | Australia | ||
| 7 | Concord Repatriation General Hospital | Concord | Australia | ||
| 8 | Frankston Hospital | Frankston | Australia | ||
| 9 | Fremantle Hospital | Fremantle | Australia | ||
| 10 | Gosford Hospital | Gosford | Australia | ||
| 11 | Royal Hobart Hospital | Hobart | Australia | ||
| 12 | Nepean Hospital | Kingswood | Australia | ||
| 13 | Lismore Base Hospital | Lismore | Australia | ||
| 14 | Liverpool Hospital | Liverpool | Australia | ||
| 15 | Alfred Hospital | Melbourne | Australia | ||
| 16 | Austin Health | Melbourne | Australia | ||
| 17 | Peter MacCallum Cancer Centre | Melbourne | Australia | ||
| 18 | St Vincent's Hospital | Melbourne | Australia | ||
| 19 | Mater Misericordiae Hospital | Newcastle | Australia | ||
| 20 | Royal Perth Hospital | Perth | Australia | ||
| 21 | Royal North Shore Hospital | St Leonards | Australia | ||
| 22 | St Vincent's Hospital | Sydney | Australia | ||
| 23 | Westmead Hospital | Westmead | Australia | ||
| 24 | Murray Valley Private Hospital | Wodonga | Australia | ||
| 25 | Wollongong Hospital | Wollongong | Australia | ||
| 26 | Princess Alexandra Hospital | Woolloongabba | Australia | ||
| 27 | Auckland Hospital | Auckland | New Zealand | ||
| 28 | Middlemore Hospital | Auckland | New Zealand | ||
| 29 | Christchurch Hospital | Christchurch | New Zealand | ||
| 30 | North Shore Hospital | Westlake | New Zealand | ||
| 31 | Birmingham Heartlands Hospital | Birmingham | England | United Kingdom | B9 5SS |
| 32 | Blackpool Victoria Hospital | Blackpool | England | United Kingdom | FY3 8NR |
| 33 | West Suffolk Hospital | Bury St. Edmunds | England | United Kingdom | IP33 2QZ |
| 34 | Kent and Canterbury Hospital | Canterbury | England | United Kingdom | CT1 3NG |
| 35 | St. Helier Hospital | Carshalton | England | United Kingdom | SM5 1AA |
| 36 | Royal Devon and Exeter Hospital | Exeter | England | United Kingdom | EX2 5DW |
| 37 | Queen Elizabeth Hospital | Gateshead | England | United Kingdom | NE9 6SX |
| 38 | Medway Maritime Hospital | Gillingham | England | United Kingdom | ME7 5NY |
| 39 | Hemel Hempstead General | Hemel Hempstead | England | United Kingdom | HP2 4AD |
| 40 | Hull Royal Infirmary | Hull | England | United Kingdom | HU3 2KZ |
| 41 | West Middlesex University Hospital | Isleworth | England | United Kingdom | TW7 6AF |
| 42 | Kettering General Hosptial | Kettering | England | United Kingdom | NNI6 8UZ |
| 43 | Kidderminster Hospital | Kidderminster | England | United Kingdom | DY11 6RJ |
| 44 | Queen Elizabeth Hospital | King's Lynn | England | United Kingdom | PE30 4ET |
| 45 | Leicester Royal Infirmary | Leicester | England | United Kingdom | LE1 5WW |
| 46 | St. George's Hospital | London | England | United Kingdom | SW17 0QT |
| 47 | Maidstone Hospital | Maidstone | England | United Kingdom | ME16 9QQ |
| 48 | Sir James Spence Institute of Child Health at Royal Victoria Infirmary | Newcastle-Upon-Tyne | England | United Kingdom | NE1 4LP |
| 49 | Mount Vernon Cancer Centre at Mount Vernon Hospital | Northwood | England | United Kingdom | HA6 2RN |
| 50 | Rosemere Cancer Centre at Royal Preston Hospital | Preston | England | United Kingdom | PR2 9HT |
| 51 | Alexandra Healthcare NHS | Redditch | England | United Kingdom | B98 7UB |
| 52 | Oldchurch Hospital | Romford | England | United Kingdom | RM7 OBE |
| 53 | Pembury Hospital | Royal Tunbridge Wells | England | United Kingdom | TN2 4QJ |
| 54 | Southampton General Hospital | Southampton | England | United Kingdom | SO16 6YD |
| 55 | Staffordshire General Hospital | Stafford | England | United Kingdom | ST16 3SA |
| 56 | Royal Marsden - Surrey | Sutton | England | United Kingdom | SM2 5PT |
| 57 | Torbay Hospital | Torquay | England | United Kingdom | TQ2 7AA |
| 58 | Royal Cornwall Hospital | Truro | England | United Kingdom | TR1 3LJ |
| 59 | Weston General Hospital | Weston-super-Mare | England | United Kingdom | BS23 4TQ |
| 60 | Worcester Royal Hospital | Worcester | England | United Kingdom | WR5 1DD |
| 61 | Aberdeen Royal Infirmary | Aberdeen | Scotland | United Kingdom | AB25 2ZN |
| 62 | Monklands General Hospital | Airdrie | Scotland | United Kingdom | ML6 0JF |
| 63 | Hairmyres Hospital | East Kilbride | Scotland | United Kingdom | G75 8RG |
| 64 | Edinburgh Cancer Centre at Western General Hospital | Edinburgh | Scotland | United Kingdom | EH4 2XU |
| 65 | Southern General Hospital | Glasgow | Scotland | United Kingdom | G51 4TF |
| 66 | Raigmore Hospital | Inverness | Scotland | United Kingdom | 1V2 3UJ |
| 67 | Royal Alexandra Hospital | Paisley | Scotland | United Kingdom | |
| 68 | Wishaw General Hospital | Wishaw | Scotland | United Kingdom | ML2 0DP |
| 69 | Velindre Cancer Center at Velindre Hospital | Cardiff | Wales | United Kingdom | CF14 2TL |
| 70 | Prince Charles Hospital | Merthyr Tydfil | Wales | United Kingdom | CF47 9DT |
| 71 | Glan Clwyd Hospital | Rhyl | Wales | United Kingdom | LL 18 5UJ |
| 72 | South West Wales Cancer Institute | Swansea | Wales | United Kingdom | SA2 8QA |
Sponsors and Collaborators
- University College, London
- Cancer Research UK
- Roche Pharma AG
Investigators
- Study Chair: Kirit Ardeshna, Mount Vernon Cancer Centre at Mount Vernon Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000427312
- CRUK-2004-001621-16
- EU-20509
- ROCHE-CRUK-001621-16