Clinical trial NCT00006250: Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Non-Hodgkin's Lymphoma
Official title: Randomized Trial of MCD Versus FMD in Untreated Advanced Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different combination chemotherapy regimens in treating patients who have stage III or stage IV non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

* Compare the overall survival rate, progression free survival rate, clinical and molecular remission rates, and time to treatment failure in patients with newly diagnosed stage III or IV follicular non-Hodgkin's lymphoma treated with chlorambucil, mitoxantrone, and dexamethasone versus fludarabine, mitoxantrone, and dexamethasone.
* Compare the efficacy and tolerability of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Index score \[low risk (score 1) vs intermediate low risk (score 2) vs intermediate high risk (score 3) vs high risk (score 4 or 5)\]. Patients are randomized to one of two treatment arms.

* Arm I: Patients receive mitoxantrone IV on day 1, oral chlorambucil on days 1-10, and oral dexamethasone on days 1-5.
* Arm II: Patients receive mitoxantrone and dexamethasone as in arm I and fludarabine IV on days 1-3.

Treatment continues every 4 weeks for 4-8 courses.

Patients are followed at 3, 6, and 12 months, every 6 months for 1 year, and then annually thereafter until clinical relapse.

PROJECTED ACCRUAL: A total of 500 patients (250 per arm) will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven newly diagnosed stage III or IV follicular non-Hodgkin's lymphoma

  * REAL classification grade I, II, or III
* Treatment necessity indicated by presence of the following:

  * B symptoms
  * Bone marrow failure
  * Bulky or progressive disease
  * Compression syndromes
* No CNS involvement

PATIENT CHARACTERISTICS:

Age:

* 18 to 70

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* No autoimmune hemolytic anemia or active hemolysis
* Direct Coombs' negative

Hepatic:

* Alkaline phosphatase no greater than 2.5 times upper limit of normal (ULN)\*
* Bilirubin no greater than 2.5 times ULN\* NOTE: \*Unless attributable to lymphoma

Renal:

* Creatinine no greater than 2.5 times ULN (unless attributable to lymphoma)

Cardiovascular:

* No severe cardiac failure
* Ejection fraction at least 45%

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception during and for at least 6 months after study
* HIV negative
* No prior malignancy except carcinoma in situ of the cervix or squamous cell skin cancer
* No other serious medical disease that would limit lifespan or ability to tolerate chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* No concurrent systemic corticosteroids

Radiotherapy:

* Not specified

Surgery:

* Not specified

Other:

* No prior therapy

Primary outcomes:
measure: Time to treatment failure
measure: Progression-free survival rate
measure: Overall survival rate
Secondary outcomes:
measure: Clinical remission rate
measure: Molecular remission rate
Other outcomes:
Locations:
city: Aylesbury-Buckinghamshire
country: United Kingdom
facility: Stoke Mandeville Hospital
state: England
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Hospitals NHS Trust
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: Chichester
country: United Kingdom
facility: Saint Richards Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Dartford Kent
country: United Kingdom
facility: Dartford & Gravesham NHS Trust, Joyce Green Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: England
city: Epsom Surrey
country: United Kingdom
facility: Epsom General Hospital
state: England
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust
state: England
city: Isleworth
country: United Kingdom
facility: West Middlesex University Hospital
state: England
city: Kettering, Northants
country: United Kingdom
facility: Kettering General Hosptial
state: England
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Leeds
country: United Kingdom
facility: Clinical Trials and Research Unit of the University of Leeds
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: St. Thomas' Hospital
state: England
city: London
country: United Kingdom
facility: St. Georges, University of London
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Pontefract West Yorkshire
country: United Kingdom
facility: Pontefract General Infirmary
state: England
city: Romford
country: United Kingdom
facility: Oldchurch Hospital
state: England
city: Rotherham
country: United Kingdom
facility: Rotherham District General Hospital - NHS Trust
state: England
city: Royal Tunbridge Wells, Kent
country: United Kingdom
facility: Pembury Hospital
state: England
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Taunton Somerset
country: United Kingdom
facility: Taunton and Somerset Hospital
state: England
city: Torquay Devon
country: United Kingdom
facility: Torbay Hospital
state: England
city: Uxbridge
country: United Kingdom
facility: Hillingdon Hospital
state: England
city: West Bromwich
country: United Kingdom
facility: Sandwell General Hospital
state: England
city: West Midlands
country: United Kingdom
facility: Good Hope Hospital Trust
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: England
city: Yeovil - Somerset
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: York
country: United Kingdom
facility: Cancer Care Centre at York Hospital
state: England
city: Belfast
country: United Kingdom
facility: Centre for Cancer Research and Cell Biology at Belfast City Hospital
state: Northern Ireland
city: Craigavon
country: United Kingdom
facility: Craigavon Area Hospital
state: Northern Ireland
city: Dundonald
country: United Kingdom
facility: Ulster Hospital
state: Northern Ireland
city: Wakefield
country: United Kingdom
facility: Pinderfields Hospital NHS Trust
state: Scotland
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clywd District General Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital of the Swansea NHS Trust
state: Wales
Study officials:
affiliation: Nottingham City Hospital
name: Andy Haynes, MD
role: STUDY_CHAIR
References: