Chemotherapy and Biological Therapy With or Without Bone Marrow or Peripheral Stem Cell Transplant in Treating Patients With Chronic Myelogenous Leukemia

Sponsor

III. Medizinische Klinik Mannheim (Other)

Overall Status

Unknown status

CT.gov ID

NCT00025402

Collaborator

(none)

1,000

Enrollment

188

Locations

5.3

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy, such as hydroxyurea, cytarabine, idarubicin, and etoposide before a donor bone marrow transplant or stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Interferon alfa may interfere with the growth of cancer cells and slow the growth of cancer. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether chemotherapy is more effective with or without interferon alfa and/or bone marrow or stem cell transplant in treating patients with chronic myelogenous leukemia.

PURPOSE: This randomized phase III trial is studying chemotherapy and biological therapy to see how well it works compared with chemotherapy, biological therapy, and donor bone marrow transplant or autologous stem cell transplant in treating patients with chronic phase chronic myelogenous leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: filgrastim Biological: recombinant interferon alfa Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Drug: etoposide Drug: hydroxyurea Drug: idarubicin Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Compare survival in patients with chronic myelogenous leukemia in early chronic phase treated with allogeneic bone marrow transplantation vs drug treatment with or without autologous peripheral blood stem cell transplantation.
Compare survival of patients with late-phase disease treated with high-dose cytarabine vs low-dose cytarabine followed by autografting and interferon alfa maintenance.
Compare survival of patients not responding cytogenetically to treatment with continued interferon alfa vs hydroxyurea.
Determine frequency, time-point, and duration of hematological and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCR-ABL-positive cells on the various treatments.
Correlate the quality of hematological and cytogenetic remissions with survival time in patients treated with these regimens.
Compare the course of the terminal phase in patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.
Determine the effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time in patients treated with these regimens.
Compare the effect of early vs late high-dose therapy plus autografting on feasibility, toxicity, and survival times in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to eligibility for transplantation (yes vs no).

All patients undergo cytoreduction comprising hydroxyurea (HU) IV daily.

Patients who are ineligible for or refuse transplantation are randomized to 1 of 2 treatment arms.

Arm I: Patients receive interferon alfa (IFN) subcutaneously (SC) daily. After 2 weeks of IFN therapy, patients also receive low-dose cytarabine (ARA-C) SC once daily for 10-15 days each month. Patients who do not achieve cytogenetic remission within 12 months continue to receive HU.
Arm II: Patients receive IFN SC daily. After 2 weeks of IFN therapy, patients also receive low-dose ARA-C SC daily for 10-15 days each month. Patients who do not achieve cytogenetic remission within 12 months continue to receive IFN therapy SC daily.

Patients who are eligible for transplantation with a related donor undergo allogeneic bone marrow transplantation. Patients may receive HU or IFN prior to transplantation. Patients may also receive oral high-dose busulfan daily for 4 days with or without cyclophosphamide or cyclophosphamide with total body irradiation.

Patients who are eligible for transplantation but do not have a related donor undergo peripheral blood stem cell (PBSC) harvest and are randomized to 1 of 2 treatment arms.

Arm III: Patients receive IFN and low-dose ARA-C as in arm I. Patients who accelerate on treatment may undergo autologous PBSC transplantation.
Arm IV: Patients receive idarubicin IV, ARA-C IV over 2 hours, and etoposide IV on days 1-3. Patients then undergo leukapheresis. Beginning on day 8, patients receive filgrastim (G-CSF) SC daily until end of leukapheresis. Patients then receive oral high-dose busulfan daily for 4 consecutive days. The following day, patients undergo reinfusion of autologous PBSC. After blood count recovery, patients receive maintenance IFN 3 times weekly for 8 weeks and then daily.

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

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within 5 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1000 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Randomized Multicenter Treatment Optimization Study In Chronic Myeloid Leukemia (CML) Interferon-a Vs. Allogeneic Stem Cell Transplantation Vs. High-Dose Chemotherapy Followed By Autografting And Interferon-a Maintainance In Early Chronic Phase

Study Start Date :

Jul 1, 1997

Outcome Measures

Primary Outcome Measures

Survival []
Frequency, time-point, and duration of hematologic and cytogenetic remissions and of Philadelphia chromosome-negative and/or BCL-ABL-positive cells []
Correlation of quality of hematological and cytogenetic remission with survival time []
Course of the terminal phase []
Toxicity []
Effect of prognostic criteria and normal or subnormal WBC on chronic phase duration and survival time []
Effect of early vs late high-dose therapy and autografting on feasibility, toxicity and survival times []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of chronic myelogenous leukemia in chronic phase
Previously untreated
Patients negative for Philadelphia chromosome and BCR-ABL translocation must fulfill at least 1 of the following criteria:
Impaired health status with reduced exercise tolerance
Spleen-related symptoms in cases of splenomegaly
Weight loss greater than 10% in 6 months
Fever greater than 38.5 degrees C on 5 consecutive days
Clinically relevant bone pain
Leukocytosis greater than 5,000/mm^3
Thrombocytosis greater than 100,000/mm^3

PATIENT CHARACTERISTICS:

Age:

Any age

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Not specified

Renal:

Not specified

Other:

No other concurrent malignancy that is likely to require treatment during study or that is likely to reduce life expectancy
No severe concurrent disease or other cause that would preclude study
Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior interferon

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy

Surgery:

Not specified

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Masaryk University Hospital	Brno	Czech Republic	62500
2	Haematologisch Onkologische Praxis	Aachen	Germany	D-52070
3	Kinderklinik - Universitaetsklinikum Aachen	Aachen	Germany	D-52074
4	Urologische Klinik - Universitaetsklinikum Aachen	Aachen	Germany	D-52074
5	Kreiskrankenhaus	Aalen	Germany	73430
6	Klinikum St. Marien	Amberg	Germany	D-92224
7	Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie	Ansbach	Germany	91522
8	II. Medizinische Klinik	Aschaffenburg	Germany	RG 63739
9	Haematologische Praxis	Augsburg	Germany	86150
10	Klinikum Augsburg	Augsburg	Germany	DOH-86156
11	Kreiskrankenhaus	Bad Hersfeld	Germany	36251
12	Krankenhaus Hohe Warte Mediziniche Klinik	Bayreuth	Germany	95445
13	St. Hedwig Kranken Haus	Berlin	Germany	10115
14	Tumorzentrum Berlin-Moabit	Berlin	Germany	10967
15	Wenckebach - Krankenhaus	Berlin	Germany	12099
16	Helios Klinikum Berlin	Berlin	Germany	13125
17	Haematologisch-Onkologische Schwerpunktpraxis	Berlin	Germany	13357
18	Charite - Campus Charite Mitte	Berlin	Germany	D-10117
19	Onkolog - Haematolog Schwerpunktpraxis	Berlin	Germany	D-10559
20	Krankenhaus Neukoelln	Berlin	Germany	D-12313
21	Charite - Campus Virchow Klinikum	Berlin	Germany	D-13353
22	Kinderklinik der Freier Universitaet Berlin	Berlin	Germany	D-14059
23	Onkologische Schwerpunktpraxis Bielefeld	Bielefeld	Germany	D-33602
24	Franziskus Hospital	Bietigheim	Germany	74321
25	Krankenhaus Bietigheim	Bietigheim	Germany	74321
26	Europahochhaus	Bochum	Germany	44787
27	Kreiskrankenhaus Boeblingen	Boeblingen	Germany	71032
28	Universitaetsklinikum Bonn	Bonn	Germany	D-53105
29	Medizinische Poliklinik	Bonn	Germany	D-53111
30	Marienhospital Bottrop gGmbH	Bottrop	Germany	D-46236
31	Staedtisches Klinikum Braunschweig	Braunschweig	Germany	D-38114
32	Klinikum Bremen-Mitte	Bremen	Germany	D-28205
33	St. Joseph Hospital	Bremerhaven	Germany	D-27568
34	Zentralkrankenhaus	Bremerhaven	Germany	N 27574
35	Medizinische Klinik Am Lukas - Krankenhaus	Buende	Germany	32257
36	Klinikum Coburg	Coburg	Germany	96450
37	Praxis Gemeinschaft	Cologne	Germany	D-50676
38	Praxis Fuer Haematologie Internistische Onkologie	Cologne	Germany	D-50677
39	Medizinische Universitaetsklinik I at the University of Cologne	Cologne	Germany
40	Onkologische Schwerpunktpraxis	Cottbus	Germany	D-03046
41	Stadt. KH Dresden - Neustadt	Dresden	Germany	01129
42	Medizinische Klinik I	Dresden	Germany	D-01307
43	Krankenhaus Dueren	Dueren	Germany	52351
44	Universitaetsklinikum Duesseldorf	Duesseldorf	Germany	D-40225
45	Michael Schaefers und Partner	Duisburg	Germany	D-47051
46	St. Johannes Hospital - Medical Klinik II	Duisburg	Germany	D-47166
47	Hans - Susemihl - Krankenhaus	Emden	Germany	26721
48	Internistiche Praxis	Erfurt	Germany	99084
49	Klinikum Erfurt	Erfurt	Germany	99089
50	Praxis DR. J. Weniger	Erfurt	Germany	D-99085
51	Onkologische Schwerpunkt Praxis	Erlangen	Germany	D-91052
52	Medizinische Klinik III - Universitaetsklinikum Erlangen	Erlangen	Germany	D-91054
53	St. Antonius Hospital	Eschweiler	Germany	DOH-52249
54	Universitaetsklinikum Essen	Essen	Germany	D-45122
55	Evangelisches Krankenhaus Essen Werden	Essen	Germany	D-45239
56	Malteser Krankenhaus	Flensburg	Germany	D-24939
57	Onkolog Gemeinschaftspraxis	Frankfurt	Germany	60389
58	Klinikum der J.W. Goethe Universitaet	Frankfurt	Germany	D-60590
59	Universitaetsklinikum Freiburg	Freiburg	Germany	D-79106
60	II Medizinische Klinik - Klinikum Fuerth	Fuerth	Germany	D-90766
61	Kreiskrankenhaus Fuessen	Fuessen	Germany	87629
62	Klinikum Garmisch - Partenkirchen GmbH	Garmisch-Partenkirchen	Germany	D-82467
63	Gemeinschaftspraxis Fuer Innere Medizin, Hematologie Und Onkologie	Giessen	Germany	35392
64	Klinik und Poliklinik fuer Urologie und Kinderurologie	Giessen	Germany	D-35392
65	Klinik fuer Radioonkologie und Strahlentherapie	Goeppingen	Germany	73035
66	Universitaetsklinikum Goettingen	Goettingen	Germany	D-37075
67	DR Herbert - Nieper Krankenhaus Goslar	Goslar	Germany	38642
68	Allgemeines Krankenhaus Hagen	Hagen	Germany	D-58095
69	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH	Hagen	Germany	D-58095
70	Allgemeines Krankenhaus Altona	Hamburg	Germany	22763
71	Hermann - Holthusen Institute for Radiotherapy	Hamburg	Germany	D-20099
72	Universitaetsklinikum Hamburg-Eppendorf	Hamburg	Germany	D-20246
73	Onkologischer Schwerpunkt Lerchenfeld	Hamburg	Germany	D-22081
74	Asklepios Klinik Barmbek	Hamburg	Germany	D-22291
75	Haematologisch-Onkologische Praxis Altona	Hamburg	Germany	D-22767
76	Evangelische Krankenhaus Hamm	Hamm	Germany	D-59063
77	St. Marien-Hospital Hamm - Klinik Knappenstrasse	Hamm	Germany	D-59071
78	Haematologie Und Internistische Onkologie	Hanau	Germany	63450
79	Krankenhaus Siloah - Medizinische Klinik II	Hannover	Germany	D-30449
80	Medizinische Hochschule Hannover	Hannover	Germany	D-30625
81	Medizinische Universitaetsklinik und Poliklinik	Heidelberg	Germany	69115
82	Klinikum Herford	Herford	Germany	D-32049
83	Universitaetsklinikum des Saarlandes	Homburg	Germany	66424
84	Clinic for Bone Marrow Transplantation and Hematology and Oncology	Idar-Oberstein	Germany	D-55743
85	Praxis am Evangelischen Krankenhaus Bethanien	Iserlohn	Germany	D-58644
86	Klinikum der Friedrich-Schiller Universitaet Jena	Jena	Germany	D-07740
87	Diakonissen - Krankenhaus	Karlsruhe-Rueppur	Germany	76199
88	Staedtisches Klinikum Karlsruhe gGmbH	Karlsruhe	Germany	76133
89	Gemeinschaftspraxis Brunoehler	Karlsruhe	Germany	76135
90	St. Vincentius-Kliniken	Karlsruhe	Germany	D-76137
91	Klinikum Kassel	Kassel	Germany	D-34125
92	Klinikum Kempten Oberallgaeu	Kempten	Germany	D-87439
93	University Hospital Schleswig-Holstein - Kiel Campus	Kiel	Germany	D-24105
94	Klinik Konstanz	Konstanz	Germany	78461
95	Haematologische / Onkologische Schwerpunktpraxis	Krefeld	Germany	47798
96	Klinikum Krefeld GmbH	Krefeld	Germany	D-47805
97	Vinzentiuskrankenhaus	Landau	Germany	D-76829
98	Caritas - Krakenhaus Lebach	Lebach	Germany	66822
99	Onkologische Schwerpunktpraxis - Leer	Leer	Germany	D-26789
100	Klinikum Lippe - Lemgo	Lemgo	Germany	D-32657
101	Luisenkrankenhaus	Lindenfels	Germany	64678
102	Klinikum der Stadt Ludwigshafen am Rhein	Ludwigshafen am Rhein	Germany	D-67063
103	St Marienkrankenhaus	Ludwigshafen, Rhein	Germany	D-67067
104	Praxis Fuer Haematologie/Onkologie	Luebeck	Germany	D-23560
105	Onkologische Schwerpunktpraxis Lueneburg	Lueneburg	Germany	D-21391
106	Gemeinschaftspraxis	Mannheim	Germany	D-68161
107	III Medizinische Klinik Mannheim	Mannheim	Germany	D-68305
108	Philipps-Universitaet Marburg Klinikum	Marburg	Germany	D-35033
109	Kreiskrankenhaus Mellrichstadt	Mellrichstad	Germany	DT-97638
110	Klinikum Minden	Minden	Germany	D-32423
111	Krankenhaus Maria Hilf GmbH	Moenchengladbach	Germany	DOH-41063
112	Universitaets - Kinderpoliklinik	Muenchen	Germany	80336
113	Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster	Muenster	Germany	D-48129
114	Gemeinschaftspraxis	Munich	Germany	80331
115		Munich	Germany	80637
116	Krankenhaus Muenchen Schwabing	Munich	Germany	80804
117	Medizinische Kl. Klinikum Innenstadt Universitaet Muenchen	Munich	Germany	D-80336
118	Praxis fuer Innere Medizin und Haematologie	Munich	Germany	D-80797
119		Munich	Germany	D-81241
120	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich	Germany	D-81377
121	Staedtisches Krankenhaus Muenchen - Harlaching	Munich	Germany	D-81545
122	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich	Germany	D-81675
123	Krankenhaus Muenchen Neuperlach	Munich	Germany	D-81737
124	Ruppiner Klinikum GMBH	Neuruppin	Germany	16816
125	Gemeinschaftspraxis	Niddatel-IIbenstadt	Germany	61194
126	Praxis fuer Haematologie und Interne Onkologie	Norderstedt	Germany	22844
127	Gemeinschaftspraxis	Nuernberg	Germany	D-90402
128	Klinikum Nuernberg - Klinikum Nord	Nuernberg	Germany	D-90419
129	Klinikum Nuernberg - Klinikum Sued	Nuernberg	Germany	D-90471
130	Hematologische Praxis	Oldenburg	Germany	26121
131	Klinikum Oldenburg	Oldenburg	Germany	D-26133
132	Paracelsus - Klinik Osnabrueck	Osnabrueck	Germany	D-49076
133	Staedtisches Krankenhaus	Pforzheim	Germany	75175
134	Kreiskrankenhaus Radebeul	Radebeul	Germany	D-01445
135	St. Elisabeth Krankenhaus	Ravensburg	Germany	88212
136	Prosper-Hospital Recklinghausen	Recklinghausen	Germany	D-45659
137	Hematologische Onkologische Praxis	Regensburg	Germany	93047
138	Krankenhaus Barmherzige Brueder Regensburg	Regensburg	Germany	D-93049
139	Klinikum der Universitaet Regensburg	Regensburg	Germany	D-93053
140	Klinikum Remscheid GmbH	Remscheid	Germany	D-42859
141	Jakobi Krankenhaus	Rheine	Germany	48431
142	Caritasklinik St. Theresia	Saarbrucken	Germany	D-66113
143	Schwerpunktpraxis fuer Haematologie und Onkologie	Saarbruecken	Germany	D-66113
144	Saechsische Schweiz Klinik	Sebnitz	Germany	D-01855
145	Staedt Krankenhaus	Sebnitz	Germany	D-01855
146	St. Marien - Krankenhaus Siegen GMBH	Siegen	Germany	D-57072
147	Kreiskrankenhaus Siegen	Siegen	Germany	D-57076
148	Klinikum Der Hansestadt Stralsund - Klin. West	Stralsund	Germany	D-18410
149	Robert-Bosch-Krankenhaus	Stuttgart	Germany	70376
150	Haematologische Praxis	Stuttgart	Germany	D-70173
151	Klinik fuer Onkologie - Katharinenhospital Stuttgart	Stuttgart	Germany	D-70174
152	Diakonie Klinikum Stuttgart	Stuttgart	Germany	D-70176
153	Krankenanstalt Mutterhaus der Borromaerinnen	Trier	Germany	D-54219
154		Trier	Germany	D-54290
155	Praxis Fuer Internistische Haematologie / Onkologie	Troisdorf	Germany	53840
156	Schwerpunktpraxis für Rheumatologie und Haematologie/Internistische Onkologie	Tuebingen	Germany	D-72072
157	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen	Germany	D-72076
158	Bundeswehr Krakenhaus	Ulm	Germany	D-89070
159	Universitaetsklinikum Ulm	Ulm	Germany	D-89081
160	St. Irmgardis Krankenhaus	Viersen-Suechteln	Germany	41749
161	Klinikum Der Stadt Villingen - Schwenningen	Villingen-Schwenningen	Germany	D-78054
162	Krankenhaus St. Michael	Voeklingen	Germany	66333
163	Kreiskrankenhaus	Waldroel	Germany	51545
164	Deutsche Klinik fuer Diagnostik	Wiesbaden	Germany	D-65191
165	St. Willehad Hospital	Wilhelmshaven	Germany	D-26382
166	Kliniken St. Antonius	Wuppertal 2	Germany	D-42283
167	Praxis Fuer Haemotologie Und Internistischer Onkologie	Wuppertal	Germany	42105
168	Helios Kliniken Wuppertal University Hospital	Wuppertal	Germany	D-42283
169	Medical University of Gdansk	Gdansk	Poland	80-211
170	Silesian Medical Academy	Katowice	Poland	40-029
171	Hospital Universitario Virgen de la Victoria	Malaga	Spain	29010
172	Kantonspital Aarau	Aarau	Switzerland	CH-5001
173	Facharzt FMH Fuer Innere Medizin and Oncology	Baar	Switzerland	CH-6340
174		Basel	Switzerland	CH 4051
175	Universitaetsspital-Basel	Basel	Switzerland	CH-4031
176	Oncology Institute of Southern Switzerland	Bellinzona	Switzerland	CH-6500
177	Facharzt Fuer Onkologie-Hematologie	Bern	Switzerland	3013
178	Inselspital Bern	Bern	Switzerland	CH-3010
179	Inneremedizin FMH	Breitenbach	Switzerland	4226
180	Bezirksspital Dornach	Dornach	Switzerland	CH-4143
181	Hopital Cantonal Universitaire de Geneve	Geneva	Switzerland	CH-1211
182	FMH f. Innere Medizin and Hematologie	Grosshochstetten	Switzerland	3506
183	Centre Hospitalier Universitaire Vaudois	Lausanne	Switzerland	CH-1011
184	Kantonsspital, Luzerne	Luzerne	Switzerland	CH-6016
185	Institut Central des Hopitaux Valaisans	Sion	Switzerland	CH-1951
186	Kantonsspital - St. Gallen	St. Gallen	Switzerland	CH-9007
187	Klinik Hirslanden	Zurich	Switzerland	CH-8008
188	UniversitaetsSpital Zuerich	Zurich	Switzerland	CH-8091