Combination Chemotherapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma

Sponsor

Lymphoma Trials Office (Other)

Overall Status

Completed

CT.gov ID

NCT00005867

Collaborator

(none)

310

Enrollment

Locations

115

Duration (Months)

6.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: bleomycin sulfate Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: mitoxantrone hydrochloride Drug: prednisolone Drug: vincristine sulfate	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

310 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Phase III Trial Comparing CHOP ot PMitCEBO in Good Risk Patients With Histologically Aggresive Non Hodgkin's Lymphoma

Study Start Date :

Jan 1, 1998

Actual Study Completion Date :

Aug 1, 2007

Outcome Measures

Primary Outcome Measures

Overall survival in patients treated with mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone (PMitCEBO) versus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) []

Secondary Outcome Measures

Failure-free survival, disease specific survival, relapse-free survival, death due to toxicity, response rate, and toxicity at 4 years []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stoke Mandeville Hospital	Aylesbury-Buckinghamshire	England	United Kingdom	HP21 8AL
2	Horton Hospital	Banbury	England	United Kingdom	OX16 9AL
3	Basildon University Hospital	Basildon	England	United Kingdom	SS16 5NL
4	Birmingham Heartlands Hospital	Birmingham	England	United Kingdom	B9 5SS
5	Bradford Hospitals NHS Trust	Bradford	England	United Kingdom	BD9 6RJ
6	Bristol Haematology and Oncology Centre	Bristol	England	United Kingdom	BS2 8ED
7	Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust	Cambridge	England	United Kingdom	CB2 2QQ
8	Cheltenham General Hospital	Cheltenham	England	United Kingdom	GL53 7AN
9	Countess of Chester Hospital NHS Foundation Trust	Chester	England	United Kingdom	CH2 1UL
10	Saint Richards Hospital	Chichester	England	United Kingdom	P019 4SE
11	Essex County Hospital	Colchester	England	United Kingdom	C03 3NB
12	Walsgrave Hospital	Coventry	England	United Kingdom	CV2 2DX
13	Russells Hall Hospital	Dudley	England	United Kingdom	DY1 2HQ
14	Chase Farm Hospital	Enfield	England	United Kingdom	EN 28 JL
15	Medway Maritime Hospital	Gillingham Kent	England	United Kingdom	ME7 5NY
16	Hull Royal Infirmary	Hull	England	United Kingdom	HU3 2KZ
17	Hinchingbrooke Hospital	Huntingdon	England	United Kingdom	PE18 6NT
18	Queen Elizabeth Hospital	King's Lynn	England	United Kingdom	PE30 4ET
19	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
20	Royal Liverpool and Broadgreen Hospitals NHS Trust	Liverpool	England	United Kingdom	L7 8XP
21	Aintree University Hospital	Liverpool	England	United Kingdom	L9 7AL
22	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
23	St. Thomas' Hospital	London	England	United Kingdom	SE1 7EH
24	St. George's Hospital	London	England	United Kingdom	SW17 0QT
25	Middlesex Hospital	London	England	United Kingdom	WC1E 6HX
26	Clatterbridge Centre for Oncology NHS Trust	Merseyside	England	United Kingdom	CH63 4JY
27	Norfolk and Norwich University Hospital	Norwich	England	United Kingdom	NR4 7UY
28	Nottingham City Hospital NHS Trust	Nottingham	England	United Kingdom	NG5 1PB
29	Oxford Radcliffe Hospital	Oxford	England	United Kingdom	0X3 9DU
30	Pontefract General Infirmary	Pontefract West Yorkshire	England	United Kingdom	WF8 1PL
31	Oldchurch Hospital	Romford	England	United Kingdom	RM7 OBE
32	Scunthorpe General Hospital	Scunthorpe	England	United Kingdom	DN15 7BH
33	Cancer Research Centre at Weston Park Hospital	Sheffield	England	United Kingdom	S1O 2SJ
34	Southampton University Hospital NHS Trust	Southampton	England	United Kingdom	SO16 6YD
35	University Hospital of North Staffordshire	Stoke-On-Trent Staffs	England	United Kingdom	ST4 6QG
36	East Surrey Hospital	Surrey	England	United Kingdom	RH1 5RH
37	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England	United Kingdom	SM2 5PT
38	Sandwell General Hospital	West Bromwich	England	United Kingdom	B71 4HJ
39	Cancer Care Centre at York Hospital	York	England	United Kingdom	Y031 8HE
40	Centre for Cancer Research and Cell Biology at Belfast City Hospital	Belfast	Northern Ireland	United Kingdom	BT9 7AB
41	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
42	Pinderfields Hospital NHS Trust	Wakefield	Scotland	United Kingdom	WF1 4DG
43	Ysbyty Gwynedd	Bangor	Wales	United Kingdom	LL57 2PW
44	University Hospital of Wales	Cardiff	Wales	United Kingdom	CF14 4XN
45	Glan Clywd District General Hospital	Rhyl, Denbighshire	Wales	United Kingdom	LL 18 5UJ
46	Mount Vernon Cancer Centre at Mount Vernon Hospital	Rhyl, Denbighshire	Wales	United Kingdom	LL 18 5UJ