Clinical trial NCT00005867: Combination Chemotherapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma
Official title: Phase III Trial Comparing CHOP ot PMitCEBO in Good Risk Patients With Histologically Aggresive Non Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: stage I grade 3 follicular lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: 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 regimen of combination chemotherapy is most effective for non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two regimens of combination chemotherapy and comparing how well they work in treating patients with aggressive non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

* Compare the overall survival, failure free survival, disease specific survival, relapse free survival, and response rate in patients with aggressive non-Hodgkin's lymphoma treated with mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone (PMitCEBO) versus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).
* Compare the early and late toxicities of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms.

* Arm I: Patients receive mitoxantrone IV, cyclophosphamide IV, and etoposide IV on day 1 and vincristine and bleomycin IV on day 8. Treatment continues every 14 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral prednisolone daily on courses 1 and 2 and every other day beginning on course 3 and continuing until the end of treatment.
* Arm II: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Treatment continues every 21 days for a maximum of 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks, then every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 310 patients (155 per arm) will be accrued for this study over 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven previously untreated bulky stage IA or stage IB-IV aggressive non-Hodgkin's lymphoma of 1 of the following types:

  * Working formulation:

    * Follicular large cell
    * Diffuse mixed cell
    * Diffuse large cell
    * Diffuse immunoblastic OR
  * REAL classification:

    * Diffuse large B-cell
    * Peripheral T-cell
* Measurable or evaluable disease
* Good prognosis defined as no more than one of the following:

  * Stage III/IV disease
  * LDH greater than upper limit of normal
  * ECOG/WHO 2-4
* No lymphoblastic or Burkitt's lymphoma
* No CNS involvement

PATIENT CHARACTERISTICS:

Age:

* 18 to 59

Performance status:

* See Disease Characteristics

Life expectancy:

* Not specified

Hematopoietic:

* Hemoglobin at least 10 g/dL
* Neutrophil count at least 2,000/mm3
* Platelet count at least 100,000/mm3

Hepatic:

* Bilirubin, AST, and ALT no greater than 1.5 times upper limit of normal

Renal:

* Creatinine no greater than 1.7 mg/dL

Cardiovascular:

* Ejection fraction at least 50% unless dysfunction attributable to lymphoma

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other concurrent serious uncontrolled medical conditions
* No other prior malignancy except adequately treated nonmelanoma skin cancer or cervical intraepithelial neoplasia

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy to more than 35% of hematopoietic sites
* Concurrent consolidation radiotherapy allowed

Surgery:

* Not specified

Primary outcomes:
measure: Overall survival in patients treated with mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone (PMitCEBO) versus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)
Secondary outcomes:
measure: Failure-free survival, disease specific survival, relapse-free survival, death due to toxicity, response rate, and toxicity at 4 years
Other outcomes:
Locations:
city: Aylesbury-Buckinghamshire
country: United Kingdom
facility: Stoke Mandeville Hospital
state: England
city: Banbury
country: United Kingdom
facility: Horton 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: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital NHS Foundation Trust
state: England
city: Chichester
country: United Kingdom
facility: Saint Richards Hospital
state: England
city: Colchester
country: United Kingdom
facility: Essex County Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: England
city: Enfield
country: United Kingdom
facility: Chase Farm Hospital
state: England
city: Gillingham Kent
country: United Kingdom
facility: Medway Maritime Hospital
state: England
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: England
city: Huntingdon
country: United Kingdom
facility: Hinchingbrooke 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: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen Hospitals NHS Trust
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: St. Thomas' Hospital
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: Middlesex Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe 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: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton University Hospital NHS Trust
state: England
city: Stoke-On-Trent Staffs
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Surrey
country: United Kingdom
facility: East Surrey Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: West Bromwich
country: United Kingdom
facility: Sandwell General 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: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
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: University Hospital of Wales
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clywd District General Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: Wales
Study officials:
affiliation: St. George's Hospital
name: Ruth Pettengell, MD
role: STUDY_CHAIR
References: