Combination Chemotherapy Followed By Radiation Therapy in Treating Patients With Aggressive Non-Hodgkin's Lymphoma

Sponsor

German High-Grade Non-Hodgkin's Lymphoma Study Group (Other)

Overall Status

Completed

CT.gov ID

NCT00053768

Collaborator

(none)

392

Enrollment

175

Locations

Arms

56.1

Duration (Months)

2.2

Patients Per Site

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. Combining more than one drug and giving the drugs in different ways may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known which combination chemotherapy regimen followed by radiation therapy is more effective in treating aggressive non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens followed by radiation therapy to compare how well they work in treating patients with aggressive non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim Drug: EPOCH regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: vincristine sulfate Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Compare the efficacy of standard-dose vs high-dose cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone followed by radiotherapy, in terms of time to treatment failure, in patients with aggressive non-Hodgkin's lymphoma.
Compare the acute and long-term toxic effects of these regimens in these patients.
Compare the complete response rate, survival and tumor control, and disease-free survival in patients treated with these regimens.
Analyze the time to relapse after radiotherapy in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to LDH levels (no greater than upper limit of normal [ULN] vs greater than ULN), initial bulky disease (yes vs no), stage (I or II vs II or IV), ECOG performance status (0 or 1 vs 2 or 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:

Arm I (Standard dose): Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5 (CHOEP) in standard doses.
Arm II (Escalated dose): Patients receive high-dose CHOEP as in arm I. Patients also receive filgrastim (G-CSF) subcutaneously on days 6-12.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of CHOEP chemotherapy, patients with initial bulky disease or extranodal involvement undergo radiotherapy 5 days a week for 4 weeks.

Patients who undergo radiotherapy are followed at 2 months after radiotherapy. All patients (including those who undergo radiotherapy) are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 389 patients were accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

392 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomised Trial Comparing Chemotherapy Mit CHOEP (Cyclophosphamid, Doxorubicin, Vincristin, Etoposid Und Prednison) In 21-Day Intervals In Standard And Escalated Doses In Patients Aged 18-60 Years Of Age With Aggresive Non-Hodgkin-Lymphomas Favourable Prognoses

Study Start Date :

Apr 1, 2002

Actual Primary Completion Date :

Dec 5, 2006

Actual Study Completion Date :

Dec 5, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CHOEP-21 CHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)	Biological: filgrastim Drug: EPOCH regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: vincristine sulfate Radiation: radiation therapy
Experimental: high CHOEP-21 High-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)	Biological: filgrastim Drug: EPOCH regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: vincristine sulfate Radiation: radiation therapy

Arm

Intervention/Treatment

Active Comparator: CHOEP-21

CHOEP-21-Schema: Cyclophosphamid (750 mg/m2 i.v. d1), Doxorubicin (50 mg/m2 i.v. d1), Vincristin (2 mg i.v. d1), Etoposid (100 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)

Biological: filgrastim

Drug: EPOCH regimen

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: etoposide

Drug: prednisone

Drug: vincristine sulfate

Radiation: radiation therapy

Experimental: high CHOEP-21

High-CHOEP-21-Schema: Cyclophosphamid (1400 mg/m2 i.v. d1), Doxorubicin (32,5 mg/m2 i.v. d1+2), Vincristin (2 mg i.v. d1), Etoposid (175 mg/m² i.v. d1-3), Prednison (100 mg p.o. d1-5)

Biological: filgrastim

Drug: EPOCH regimen

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: etoposide

Drug: prednisone

Drug: vincristine sulfate

Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

Time to treatment failure (TTF) at first relapse [3 years within study and periodically after study completion]
Time to Treatment failure using the Kaplan_Meier-Method

Secondary Outcome Measures

Complete response rate at first relapse [3 years within study and periodically after study completion]
Number of complete remission (CR) and unconfirmed complete Remission (CRu)
Survival time [3 years within study and periodically after study completion]
Time till death (whatever cause)
Tumor control [thought the treatment]
Calcution of treatment Duration using the Kaplan-Meier method
Disease-free survival [3 years within study and periodically after study completion]
Time of disease-free survivial

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed aggressive non-Hodgkin's lymphoma
Previously untreated disease
Favorable prognosis
International Prognostic Index score of 0-1
No more than 25% marrow involvement

PATIENT CHARACTERISTICS:

Age

18 to 60

Performance status

ECOG 0-3 OR
Karnofsky 40-100%

Life expectancy

Not specified

Hematopoietic

Platelet count at least 100,000/mm^3
WBC at least 2,500/mm^3

Hepatic

No active hepatitis infection

Renal

Not specified

Other

HIV negative
Not pregnant or nursing
No relevant accompanying disease
No other concurrent malignancy
No contraindications to any study medications
No prior noncompliance by patient

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy

Surgery

Not specified

Other

No other concurrent participation in another treatment study

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Haematologisch Onkologische Praxis	Aachen	Germany	52070
2	Klinikum St. Marien	Amberg	Germany	D-92224
3	Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie	Ansbach	Germany	D-91522
4	Specialist Practice for Oncology	Aschaffenburg	Germany	63739
5	II. Medizinische Klinik	Aschaffenburg	Germany	D-63739
6	Haematologische Praxis	Augsburg	Germany	86150
7	Hamatologische/Onkologische Gemeinschaftspraxis - Augsburg	Augsburg	Germany	86150
8	Klinikum Augsburg	Augsburg	Germany	D-86156
9	Kreiskrankenhaus Aurich	Aurich	Germany	D-26603
10	Kreiskrankenhaus	Bad Hersfeld	Germany	D-36251
11	Humaine - Clinic	Bad Saarow	Germany	D-15526
12	Krankenhaus Hohe Warte Mediziniche Klinik	Bayreuth	Germany	D-95445
13	Onkolog - Haematolog Schwerpunktpraxis	Berlin	Germany	13357
14	Charite - Campus Charite Mitte	Berlin	Germany	D-13125
15	Hospital Complex Bernburg	Bernburg	Germany	D-06406
16	Krankenhaus Bietigheim	Bietigheim	Germany	D-74319
17	Saint Agnes Hospital	Bocholt	Germany	D-46397
18	Saint Josef Hospital	Bochum	Germany	D-44791
19	Knappschaft Krankenhaus	Bochum	Germany	D-44892
20	Medizinische Poliklinik	Bonn	Germany	D-53111
21	Rheinische Friedrich-Wilhelms-Universitat	Bonn	Germany	D-53113
22	DIAKO Ev. Diakonie Krankenhaus gGmbH	Bremen	Germany	D-28239
23	Medizinische Klinik Am Lukas - Krankenhaus	Bunde	Germany	D-32257
24	General Hospital	Celle	Germany	D-29223
25	Hospital Kuchwald Chemnitz	Chemnitz	Germany	D-09113
26		Cologne-Kalk	Germany	D-51105
27	Carl - Thiem - Klinkum Cottbus	Cottbus	Germany	D-03048
28	Klinikum Darmstadt	Darmstadt	Germany	D-64283
29	Saint Johannes Hospital Dortmund	Dortmund	Germany	D-44137
30	Universitatsklinikum Carl Gustav Carus	Dresden	Germany	D-01307
31	Florence-Nightingale-Krankenhause, Deaconess Kaiserswerth	Duesseldorf	Germany	D-40489
32	St. Johannes Hospital - Medical Klinik II	Duisburg	Germany	D-47166
33	Franz Hospital Dulmen	Dulmen	Germany	D-48249
34	Hans - Susemihl - Krankenhaus	Emden	Germany	D-26721
35	Klinikum Erfurt	Erfurt	Germany	99089
36	St. Antonius Hospital	Eschweiler	Germany	52249
37	Universitaetsklinikum Essen	Essen	Germany	D-45147
38	Evangelisches Krankenhaus Essen-Werden	Essen	Germany	D-45239
39	Klinikum Frankfurt (Oder) GmbH	Frankfurt/Oder	Germany	15236
40	Krankenhaus Nordwest	Frankfurt	Germany	60488
41	Evang. Deaconess Hospital Freiburg	Freiburg	Germany	D-79110
42	Municipal Hospital Complex	Fulda	Germany	36043
43	Robert - Koch Hospital	Gehrden	Germany	30989
44	Centre for Internal Medicine Gießen	Gießen	Germany	D-35392
45	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald	Germany	D-17489
46	Staedtisches Klinikum Guetersloh	Gutersloh	Germany	33332
47	Universitaetsklinikum Göttingen	Göttingen	Germany	D-37075
48	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH	Hagen	Germany	58095
49	Allgemeines Krankenhaus Hagen	Hagen	Germany	D-58095
50	Krankenhaus St. Elisabeth und St. Barbara	Halle/Saale	Germany	06110
51	Krankenhaus Martha-Maria Halle-Doelau gGmbH	Halle	Germany	06120
52	Universitaetsklinikum Halle	Halle	Germany	D-06097
53		Hamburg	Germany	20095
54	Universitaetsklinikum Hamburg-Eppendorf	Hamburg	Germany	D-20251
55	Asklepios Klinik Nord Heidberg	Hamburg	Germany	D-22413
56	Allgemeines Krankenhaus Altona	Hamburg	Germany	D-22763
57	Haematologisch-Onkologische Praxis Altona	Hamburg	Germany	D-22767
58	Evangelische Krankenhaus Hamm	Hamm	Germany	D-59063
59		Hannover	Germany	30159
60	Krankenhaus Siloah - Medizinische Klinik II	Hannover	Germany	30449
61	Henriettenstiftung Krankenhaus	Hannover	Germany	30559
62	Medizinische Hochschule Hannover	Hannover	Germany	30625
63	Oncology Specialists Clinic	Harrislee	Germany	D-24955
64	Medizinische Universitaetsklinik und Poliklinik	Heidelberg	Germany	69115
65	Thoraxklinik Heidelberg	Heidelberg	Germany	D-69126
66	Regional Hospital Heidenheim	Heidenheim	Germany	89522
67	Regional Hospital Am Plattenwald - Bad Friedrichhall	Heilbronn	Germany	D-74172
68	Klinikum Herford	Herford	Germany	32049
69	Marienhospital at Ruhr University Bochum	Herne	Germany	44625
70	Privatklinik Dr. R. Schindlbeck GmbH & Co. KG	Herrsching Am Ammersee	Germany	D-82211
71	Onkologische Schwerpunktpraxis	Hildesheim	Germany	31134
72	Evang. Hospital	Holzminden	Germany	D-37603
73	Medical University Hospital Homburg	Homburg	Germany	66421
74	Universitaetsklinikum des Saarlandes	Homburg	Germany	D-66424
75	Hospital Complex Hoyerswerda	Hoyerswerda	Germany	D-02977
76	Gemeinschaftspraxis Innere Medizin	Jena	Germany	D-07743
77	Klinikum der Friedrich-Schiller Universitaet Jena	Jena	Germany	D-07747
78	Municipal Hospital Complex of the University	Kaiserslautern	Germany	D-67655
79	Staedtisches Klinikum Karlsruhe gGmbH	Karlsruhe	Germany	D-76133
80	Red Cross Hospital Kassel	Kassel	Germany	D-34121
81	Staedtisches Krankenhaus Kiel	Kiel	Germany	D-23116
82	Praxis fuer Haematologie und Onkologie	Koblenz	Germany	D-56068
83	Stiftungsklinikum Mittelrhein - Gesundheitszentrum Evangelisches Stift Sankt Martin Koblenz gGmbH	Koblenz	Germany	D-56068
84	Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim	Koln-Merheim	Germany	D-51109
85	Praxis Fuer Haematologie Internistische Onkologie	Koln	Germany	D-50677
86	Medizinische Universitaetsklinik I at the University of Cologne	Koln	Germany	D-50924
87	Leonardis Clinic	Kornwestheim	Germany	D-70806
88	Klinikum Krefeld GmbH	Krefeld	Germany	D-47805
89	Frankenwald Klinik	Kronach	Germany	D-96317
90	Caritas - Krakenhaus Lebach	Lebach	Germany	D-66822
91	Medizinische Klinik und Poliklinik III - Universitaetsklinikum Leipzig	Leipzig	Germany	D-04103
92	University Leipzig Clinic of Internal Medicine	Leipzig	Germany	D-04103
93		Leipzig	Germany	D-04103
94	Staedtisches Klinikum "St. Georg" Leipzig	Leipzig	Germany	D-04129
95	Klinikum Lippe - Lemgo	Lemgo	Germany	D-32657
96	St. Vincenz Hospital Limburg	Limburg	Germany	D-65549
97	St. Bonifatius Hospital Lingen	Lingen	Germany	D-49808
98	Dreifaltigkeits Hospital	Lippstadt	Germany	D-59555
99	Klinikum Ludwigsburg	Ludwigsburg	Germany	D-71460
100	Klinikum der Stadt Ludwigshafen am Rhein	Ludwigshafen	Germany	D-67063
101	St. Marien Hospital Ludwighafen	Ludwigshafen	Germany	D-67067
102	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck	Luebeck	Germany	D-23538
103	Staedtisches Klinikum Magdeburg - Altstadt	Magdeburg	Germany	D-39104
104	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg	Germany	D-39120
105	Johannes Gutenberg University	Mainz	Germany	D-55131
106	German CML Study Group	Manheim	Germany	D-68305
107		Marburg	Germany	D-35037
108	Philipps-Universitaet Marburg Klinikum	Marburg	Germany	D-35043
109	Regional Hospital Mayen	Mayen	Germany	D-56727
110	Klinikum Minden	Minden	Germany	D-32423
111		Minden	Germany	D-32427
112	Ev. Hospital Bethesda	Monchenglabach	Germany	D-41061
113	Hospital Maria-Hilf II	Monchengladbach	Germany	D-41063
114		Monchenglasbach/Rheydt	Germany	D-41239
115	St. Marien Hospital - Muelheim an der Ruhr	Mulheim/Ruhr	Germany	D-45468
116	Kreiskrankenhaus Muenchberg	Munchberg	Germany	D-95213
117	Munich Oncologic Practice at Elisenhof	Munchen	Germany	D-80335
118	Klinikum der Universitaet Muenchen - Innenstadt Campus	Munchen	Germany	D-80336
119	Krankenhaus Muenchen Schwabing	Munich	Germany	D-80804
120	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich	Germany	D-81377
121	Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster	Munster	Germany	D-48129
122	Evangelisches Krankenhaus - Mülheim	Mülheim	Germany	D-45466
123	Regional Hospital Neumarkt	Neumarkt	Germany	D-92318
124	Staedtisches Klinikum Neunkirchen gGmbH	Neunkirchen	Germany	D-66538
125	Lukaskrankenhaus Neuss	Neuss	Germany	D-41464
126	Klinikum Nuernberg - Klinikum Nord	Nurnberg	Germany	D-90340
127	Klinikum Offenburg	Offenburg	Germany	D-77654
128	Hematologische Praxis	Oldenburg	Germany	D-26121
129	Ev. Hospital Oldenburg	Oldenburg	Germany	D-26122
130	Klinikum Oldenburg	Oldenburg	Germany	D-26133
131	Paracelsus - Klinik Osnabrück	Osnabrück	Germany	D-49076
132	Municipal Hospital Complex	Pforzheim	Germany	D-49 7231 9690
133	Klinikum Ernst Von Bergmann	Potsdam	Germany	D-14467
134	Kreiskrankenhaus Radebeul	Radebeul	Germany	D-01445
135	Krankenhaus St. Elisabeth - Ravensburg	Ravensburg	Germany	D-88212
136	Klinikum der Universitaet Regensburg	Regensburg	Germany	D-93042
137	Hematologische Onkologische Praxis	Regensburg	Germany	D-93047
138	Krankenhaus Barmherzige Brueder Regensburg	Regensburg	Germany	D-93049
139	Jakobi Krankenhaus	Rheine	Germany	D-48431
140	Klinik und Poliklinik fuer Innere Medizin - Universitaet Rostock	Rostock	Germany	D-18057
141	Klinik und Poliklinik fuer Strahlentherapie - Universitaetsklinikum Rostock	Rostock	Germany	D-18057
142		Rostock	Germany	D-18257
143	Caritasklinik St. Theresia	Saarbrucken	Germany	D-66113
144	Schwerpunktpraxis fuer Haematologie und Onkologie	Saarbrucken	Germany	D-66113
145	St. Elizabeth-Klinik Saarlouis	Saarlouis	Germany	D-66713
146	Martin - Luther Hospital	Schleswig	Germany	D-24837
147	Deaconess Hospital	Schwabisch Hall	Germany	D-74523
148	Leopoldina - Krankenhaus	Schweinfurt	Germany	D-97422
149	Evang. Jung-Stilling Hospital	Siegen	Germany	D-57074
150	St. Lukas - Clinic Solingen	Solingen	Germany	D-42697
151	Klinik fuer Onkologie - Katharinenhospital Stuttgart	Stuttgart	Germany	D-70174
152	Diakonie Klinikum Stuttgart	Stuttgart	Germany	D-70176
153	Klinikum Stuttgart - Buergerhospital	Stuttgart	Germany	D-70191
154	Hospital Bad Cannstatt	Stuttgart	Germany	D-70374
155	Robert-Bosch-Krankenhaus	Stuttgart	Germany	D-70376
156	St. Elisabeth Hospital Thuine	Thuine	Germany	D-49832
157	Regional Hospital Traunstein	Traunstein	Germany	D-83278
158	Krankenanstalt Mutterhaus der Borromaerinnen	Trier	Germany	D-54290
159		Trier	Germany	D-54290
160	Krankenhaus Der Barmherzigen Brueder	Trier	Germany	D-54292
161	Hospital Tutzing	Tutzing	Germany	D-82327
162	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm	Germany	D-89081
163	Ev. Hospital Unna	Unna	Germany	D-59403
164	St. Marienhospital - Vechta	Vechta	Germany	D-49377
165	Klinikum Der Stadt Villingen - Schwenningen	Villingen-Schwenningen	Germany	D-78045
166	Regional Hospital Waldbrol	Waldbrol	Germany	D-51545
167	Hospital Wetzler	Wetzlar	Germany	D-35578
168	Deutsche Klinik fuer Diagnostik	Wiesbaden	Germany	D-65191
169	Dr. Horst-Schmidt-Kliniken	Wiesbaden	Germany	D-65199
170	Ev. Hospital Witten-Herdecke	Witten	Germany	D-58455
171	University Wurzburg	Wuerzburg	Germany	D-97070
172	Kliniken St. Antonius	Wuppertal	Germany	D-42283
173	Municipal Hospital Complex Zwickau	Zwickau	Germany	D-08060
174	UniversitaetsSpital Zuerich	Zurich	Switzerland	CH-8091
175	City Hospital Triemli	Zurich	Switzerland	D-8063