Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00049595
• Collaborator: Lymphoma Trials Office (Other), Lymphoma Study Association (Other), Grup per l'Estudi dels Limfomes de Catalunya i Balears (Other), NCIC Clinical Trials Group (Other), Australasian Leukaemia and Lymphoma Group (Other), Nordic Lymphoma Group (Other)
• Enrollment: 552
• Locations: 140
• Arms: 2
• Patients Per Site: 3.9

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. Combining more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating stage III or stage IV Hodgkin's lymphoma.

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

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: bleomycin sulfate; Biological: filgrastim; Biological: pegfilgrastim; Drug: ABVD regimen; Drug: BEACOPP regimen; Drug: cyclophosphamide; Drug: dacarbazine; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: prednisone; Drug: procarbazine hydrochloride; Drug: vinblastine sulfate; Drug: vincristine sulfate	Phase 3

Detailed Description

OBJECTIVES:

• Compare event-free survival of patients with stage III or IV Hodgkin's lymphoma treated with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone vs doxorubicin, bleomycin, vinblastine, and dacarbazine.

• Compare complete response, disease-free survival, and overall survival of patients treated with these regimens.

• Compare quality of life of patients treated with these regimens.

• Compare occurrence of second malignancies in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Score (3 vs 4 or more) and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I (BEACOPP): Patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV on day 1; etoposide IV over 30 minutes on days 1-3; oral procarbazine on days 1-7; oral prednisone on days 1-14; and vincristine IV and bleomycin IV or intramuscularly (IM) on day 8. Patients may receive dexamethasone in place of prednisone. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until blood counts recover or pegfilgrastim SC on day 9 only. Treatment repeats every 22 days for 8 courses (4 courses escalated dose followed by 4 courses baseline dose) in the absence of disease progression or unacceptable toxicity.

• Arm II (ABVD): Patients receive doxorubicin IV over 5 minutes, bleomycin IV or IM, vinblastine IV, and dacarbazine IV over 5-10 minutes on days 1 and 15. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at the end of therapy, and then annually for 10 years.

Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 550 patients (225 per treatment arm) will be accrued for this study within 5.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 552 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: BEACOPP (4 Cycles Escalated + 4 Cycles Baseline) Versus ABVD (8 Cycles) In Stage III & IV Hodgkin's Lymphoma
• Actual Study Start Date: Aug 1, 2002
• Actual Primary Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ABVD 8 cycles of ABVD	Biological: bleomycin sulfate; Drug: ABVD regimen; Drug: dacarbazine; Drug: doxorubicin hydrochloride; Drug: vinblastine sulfate
Experimental: BEACOPP 4 cycles of BEACOPP Escalated + 4 cycles of BEACOPP Baseline	Biological: bleomycin sulfate; Biological: filgrastim; Biological: pegfilgrastim; Drug: BEACOPP regimen; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: prednisone; Drug: procarbazine hydrochloride; Drug: vincristine sulfate

Outcome Measures

Primary Outcome Measures

1. Event-free survival [from randomization to early discontinuation of protocol treatment, no CR/CRu after 8 cycles, relapse, progression or death]

Secondary Outcome Measures

1. Complete response as assessed by Cheson criteria adapted to Hodgkin's lymphoma [from randomization till end of treatment]

2. Disease-free survival in patients with complete response [from the day of first documentation of CR to the day of relapse]

3. Overall survival [from the date of randomization to the date of death]

4. Quality of life as assessed by European Organization for Research of the Treatment of Cancer (EORTC) Quality of Life Questionnaire (QoLQ) C30 version 3.0 [from one week prior to randomization till 10 years after end of treatment or death]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma

• No lymphocyte predominant, nodular type (nodular paragranuloma)

• Clinical stage III or IV disease

• At least 1 bidimensionally measurable target lesion or extranodal lesion

• International Prognostic Score of at least 3

PATIENT CHARACTERISTICS:

Age

• 16 to 60

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 2,000/mm^3

• Platelet count greater than 100,000/mm^3

Hepatic

• No prior uncontrolled hepatitis B viral infection

• Bilirubin no greater than 2.5 times normal (unless due to Hodgkin's lymphoma)

Renal

• Creatinine no greater than 2.0 mg/dL (unless due to Hodgkin's lymphoma)

Cardiovascular

• No severe cardiac disease that would limit normal life expectancy or preclude study

• LVEF at least 50%

Pulmonary

• No severe pulmonary disease that would limit normal life expectancy or preclude study

• Respiratory function at least 30%

Other

• HIV negative

• HTLV1 negative

• No severe active infection

• No severe neurological or metabolic disease that would limit normal life expectancy or preclude study

• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix

• No psychological, familial, sociological, or geographical condition that would preclude study

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• No prior therapy for Hodgkin's lymphoma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Canberra Hospital	Woden	Australian Capital Territory	Australia	2606
2	Nepean Cancer Care Centre at Nepean Hospital	Kingswood	New South Wales	Australia	2747
3	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales	Australia	2145
4	Princess Alexandra Hospital	Brisbane	Queensland	Australia	4102
5	Peter MacCallum Cancer Centre	East Melbourne	Victoria	Australia	3002
6	St. Vincent's Hospital - Melbourne	Fitzroy	Victoria	Australia	3065
7	Royal Perth Hospital	Perth	Western Australia	Australia	6000
8	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerp		Belgium	2020
9	AZ Sint-Jan	Brugge		Belgium	8000
10	Institut Jules Bordet	Brussels		Belgium	1000
11	Hopital Universitaire Erasme	Brussels		Belgium	1070
12	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
13	Centre Hospitalier Universitaire Brugmann	Brussels		Belgium	B 1020
14	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi		Belgium	6000
15	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	B-2650
16	Algemeen Ziekenhuis Sint Lucas	Ghent		Belgium	B-9000
17	Hopital de Jolimont	Haine Saint Paul		Belgium	7100
18	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
19	Centre Hospitalier Regional de la Citadelle	Liege		Belgium	4000
20	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir		Belgium	5530
21	H. Hartziekenhuis - Roeselaere	Roeselare		Belgium	8800
22	Tom Baker Cancer Centre - Calgary	Calgary	Alberta	Canada	T2N 4N2
23	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
24	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
25	Centre Hospitalier De Dunkerque - CHD	Winnipeg	Manitoba	Canada	R3E 0V9
26	Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6ZB
27	Doctor H. Bliss Murphy Cancer Centre	St. Johns	Newfoundland and Labrador	Canada	A1B 3V6
28	Nova Scotia Cancer Centre	Halifax	Nova Scotia	Canada	B3H 1V7
29	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
30	London Regional Cancer Program at London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
31	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario	Canada	K1H 8L6
32	Northeastern Ontario Regional Cancer Centre	Sudbury	Ontario	Canada	P3E 5J1
33	Edmond Odette Cancer Centre at Sunnybrook	Toronto	Ontario	Canada	M4N 3M5
34	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
35	Windsor Regional Cancer Centre at Windsor Regional Hospital	Windsor	Ontario	Canada	N8W 2X3
36	Hopital Charles Lemoyne	Greenfield Park	Quebec	Canada	J4V 2H1
37	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada	H1T 2M4
38	Hopital Notre-Dame du CHUM	Montreal	Quebec	Canada	H2L 4M1
39	CHUM - Hotel Dieu Hospital	Montreal	Quebec	Canada	H2L-4M1
40	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6
41	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec	Canada	G1R 2J6
42	Hopital du Saint-Sacrement - Quebec	Quebec City	Quebec	Canada	G1S 4L8
43	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4
44	University Hospital Rebro	Zagreb		Croatia	41000
45	Thomayer's University Hospital	Prague		Czechia	14000
46	Centre Hospitalier d'Annecy	Annecy		France	74011 Cedex
47	Centre Hospitalier de la Cote Basque	Bayonne		France	64100
48	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon		France	25030
49	Institut Bergonie	Bordeaux		France	33076
50	Polyclinique Bordeaux Nord Aquitaine	Boucher		France	33300
51	C.H. Bourg En Bresse	Bourg En Bresse		France	01012
52	CHU de Caen	Caen		France	14033
53	Polyclinique Du Parc	Caen		France	14052
54	Centre Regional Francois Baclesse	Caen		France	14076
55	Centre Hospitalier Regional de Chambery	Chambery		France	73011
56	Hopital d'Instruction des Armees Percy	Clamart		France	92140
57	Hopital Antoine Beclere	Clamart		France	92141
58	CHR Clermont Ferrand, Hotel Dieu	Clermont-Ferrand		France	63003
59	Hopital Louis Pasteur	Colmar		France	68024
60	Centre Hospitalier Sud Francilien - Site Corbeil	Corbeil		France	91100
61	Centre Hospitalier Universitaire Henri Mondor	Creteil		France	94010
62	Hopital Du Bocage	Dijon		France	21034
63	Institut Prive de Cancerologie	Grenoble		France	38100
64	Hopital Andre Mignot	Le Chesnay		France	78157
65	Hopital Saint Antoine Lille	Lille		France	59000
66	Centre Hospitalier Regional et Universitaire de Lille	Lille		France	59037
67	Centre Hospital Regional Universitaire de Limoges	Limoges		France	87042
68	Centre Leon Berard	Lyon		France	69373
69	Hopital Edouard Herriot - Lyon	Lyon		France	69437
70	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille		France	13273
71	Centre Hospitalier de Meaux	Meaux		France	77104
72	Centre Hospitalier Marc Jacquet	Melun		France	77011
73	Hopital Notre-Dame de Bon Secours	Metz		France	55038
74	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier		France	34298
75	Centre Hospitalier de Mulhouse	Mulhouse		France	68051
76	Centre Antoine Lacassagne	Nice		France	06189
77	Hopital de l'Archet CHU de Nice	Nice		France	F-06202
78	Hotel Dieu de Paris	Paris		France	75181
79	Institut Curie Hopital	Paris		France	75248
80	Hopital Saint-Louis	Paris		France	75475
81	Hopital Saint Antoine	Paris		France	75571
82	CHU Pitie-Salpetriere	Paris		France	75651
83	Hopital Cochin	Paris		France	75674
84	Hopital Necker	Paris		France	75743
85	Hopital Haut Leveque	Pessac		France	33604
86	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
87	Hopital Rene Dubos	Pontoise		France	95300
88	Institut Jean Godinot	Reims		France	51056
89	Hopital Sud	Rennes		France	35056
90	Centre Henri Becquerel	Rouen		France	76038
91	Centre Rene Huguenin	Saint Cloud		France	92211
92	CHU Sainte-Etienne - Hopital Bellevue	Saint Etienne		France	42055
93	Hopital de Saint Germain-en-Laye	Saint Germain-en-Laye		France	78104
94	Hopital Universitaire Hautepierre	Strasbourg		France	67098
95	Hopital Foch	Suresnes		France	92151
96	Centre Hospitalier Valence	Valence		France	26000
97	Centre Hospitalier de Valenciennes	Valenciennes		France	59300
98	CHU de Nancy - Hopitaux de Brabois	Vandoeuvre-Les-Nancy		France	54511
99	Hopital Paul Brousse	Villejuif		France	94804
100	Institut Gustave Roussy	Villejuif		France	F-94805
101	National Institute of Oncology	Budapest		Hungary	1122
102	HagaZiekenhuis - Locatie Leyenburg	's-Gravenhage		Netherlands	2545 CH
103	Jeroen Bosch Ziekenhuis	's-Hertogenbosch		Netherlands	5211 NL
104	Meander Medisch Centrum	Amersfoort		Netherlands	3816 CP
105	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam		Netherlands	1066 CX
106	Onze Lieve Vrouwe Gasthuis	Amsterdam		Netherlands	1091 HA
107	Academisch Medisch Centrum at University of Amsterdam	Amsterdam		Netherlands	1105 AZ
108	Reinier de Graaf Group - Delft	Delft		Netherlands	NL 2600 GA
109	Medisch Spectrum Twente	Enschede		Netherlands	7500 KA
110	University Medical Center Groningen	Groningen		Netherlands	9713 EZ
111	Atrium Medical Centre - Heerlen	Heerlen		Netherlands	6419 PC
112	Leiden University Medical Center	Leiden		Netherlands	2300 CA
113	Academisch Ziekenhuis Maastricht	Maastricht		Netherlands	6202 AZ
114	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen		Netherlands	NL-6500 HB
115	Saint Laurentius Ziekenhuis	Roermond		Netherlands	6043 CV
116	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam		Netherlands	3008 AE
117	University Medical Center Utrecht	Utrecht		Netherlands	3584 CX
118	Auckland City Hospital	Auckland		New Zealand	1
119	Waikato Hospital	Hamilton		New Zealand	2020
120	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw	Warsaw		Poland	02-781
121	Hospital de la Santa Cruz i Sant Pau	Barcelona		Spain	08025
122	Hospital Clinic de Barcelona	Barcelona		Spain	08036
123	Hospital Universitari Germans Trias i Pujol	Barcelona		Spain	08916
124	Sahlgrenska University Hospital	Gothenburg (Goteborg)		Sweden	S-413 45
125	University Hospital of Linkoping	Linkoping		Sweden	S-581 85
126	Lund University Hospital	Lund		Sweden	S-22185
127	Karolinska University Hospital - Huddinge	Stockholm		Sweden	S-141 86
128	Umea Universitet	Umea		Sweden	S-901 85
129	Uppsala University Hospital	Uppsala		Sweden	S-75185
130	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England	United Kingdom	B15 2TH
131	Raigmore Hospital	Birmingham	England	United Kingdom	B15 2TH
132	Kent and Canterbury Hospital	Canterbury	England	United Kingdom	CT2 7NR
133	Hull Royal Infirmary	Hull	England	United Kingdom	HU3 2KZ
134	Kettering General Hosptial	Kettering, Northants	England	United Kingdom	NNI6 8UZ
135	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
136	Middlesex Hospital	London	England	United Kingdom	WC1E 6HX
137	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England	United Kingdom	HA6 2RN
138	Nottingham City Hospital NHS Trust	Nottingham	England	United Kingdom	NG5 1PB
139	Cancer Research Centre at Weston Park Hospital	Sheffield	England	United Kingdom	S1O 2SJ
140	Staffordshire General Hospital	Stafford	England	United Kingdom	ST16 3SA

Sponsors and Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC
• Lymphoma Trials Office
• Lymphoma Study Association
• Grup per l'Estudi dels Limfomes de Catalunya i Balears
• NCIC Clinical Trials Group
• Australasian Leukaemia and Lymphoma Group
• Nordic Lymphoma Group

Investigators

• Study Chair: Patrice P. Carde, MD, Gustave Roussy, Cancer Campus, Grand Paris
• Study Chair: David C. Linch, Middlesex Hospital
• Study Chair: Marine Divine, MD, Centre Hospitalier Universitaire Henri Mondor
• Study Chair: Anna Sureda, Hospital de la Santa Cruz i Sant Pau
• Study Chair: Ralph M. Meyer, MD, FRCPC, Margaret and Charles Juravinski Cancer Centre
• Study Chair: David Ma, MD, St. Vincent's Hospital-Manhattan
• Study Chair: Devinder Gill, MD, Princess Alexandra Hospital
• Study Chair: Bengt Glimelius, MD, Uppsala University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• ClinicalTrials.gov Identifier: NCT00049595
• Other Study ID Numbers: EORTC-20012; EORTC-20012; GELA-EORTC-20012; BNLI-EORTC-20012; GELCAB-EORTC-20012; NORDICLG-EORTC-20012; CAN-NCIC-EORTC-20012; ALLG-HD04; 2004-001558-10
• First Posted: Jan 27, 2003
• Last Update Posted: Feb 15, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC: adult lymphocyte depletion Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Prednisone; Cyclophosphamide; Dacarbazine; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Bleomycin; Vinblastine; Procarbazine

Study Results

No Results Posted as of Feb 15, 2021