Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active Any age Other III-MK-CML-IV EU-20248, NCT00055874

Objectives

1. Compare the hematologic, cytogenetic, and molecular response rates in patients with newly diagnosed chronic phase chronic myelogenous leukemia treated with imatinib mesylate alone or with interferon alfa or low-dose cytarabine vs interferon alfa standard therapy.
2. Compare the group-dependent, progression-free and overall survival and time to progression in patients treated with these regimens.
3. Compare the efficacy of allogeneic stem cell transplantation vs imatinib mesylate-based therapy in patients eligible for transplantation.
4. Compare the efficacy of reduced-intensity conditioning vs standard conditioning in patients over 45 years of age.
5. Determine the time to and duration of hematologic, cytogenetic, and molecular responses and correlate these factors in patients treated with these regimens.
6. Compare the short- and long-term adverse effects of these regimens in these patients.
7. Compare the presentation, duration, and responses to therapy of accelerated and blastic phases in patients treated with these regimens.
8. Determine the survival of high-risk patients after early allografting.
9. Determine the influence of pre-transplantation therapies on the outcome of allogeneic stem cell transplantation in these patients.

Entry Criteria

Disease Characteristics:

• Newly diagnosed chronic phase chronic myelogenous leukemia (CML)
  • bcr-abl positive
  • No blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood



• Availability of a HLA-identical sibling or unrelated donor

Prior/Concurrent Therapy:

Biologic therapy

• No prior interferon

Chemotherapy

• No prior chemotherapy other than hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• Prior anagrelide allowed
• No participation in another clinical trial

Patient Characteristics:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No second malignancy requiring therapy
• No evidence of disease-related symptoms or extramedullary disease (including hepatosplenomegaly)
• No serious diseases that would preclude study participation

Expected Enrollment

A total of 1,600 patients (400 per treatment arm) will be accrued for this study within 4-5 years.

Outcomes

Overall survival
Risk group-dependent survival
Progression-free survival
Hematologic, cytogenetic, and molecular response rates

Adverse drug effects
Quality of life

Outline

This is a randomized, multicenter, pilot study. Patients are stratified according to participating center. Patients with low- to intermediate-risk disease are randomized to 1 of 4 treatment arms. Patients with high-risk disease are randomized to 1 of 3 treatment arms with imatinib mesylate-based regimens.

• Arm I: Patients receive oral imatinib mesylate once daily for up to 12 months in the absence of disease progression or unacceptable toxicity.



• Arm II: Patients receive oral imatinib mesylate as in arm I. Patients also receive interferon alfa subcutaneously (SC) 3 times a week beginning at least 3 months after the start of imatinib mesylate.



• Arm III: Patients receive oral imatinib mesylate as in arm I. Patients also receive cytarabine SC up to twice daily for 5 days monthly beginning at least 3 months after the start of imatinib mesylate.



• Arm IV: After initial cytoreduction with hydroxyurea, patients receive interferon alfa SC daily with or without hydroxyurea. In the absence of a complete response after 3 months, patients may also receive low-dose cytarabine SC once daily. Treatment continues for up to 21 months.

Patients who fail interferon alfa therapy are crossed over to receive imatinib mesylate.

Patients who fail therapy with imatinib mesylate and are eligible for an allogeneic transplantation are stratified according to availability of donor (HLA-identical related vs unrelated), status, and participating center. Patients are randomized to receive an allogeneic transplantation or continue any salvage therapy.

Patients who are not eligible for allogeneic transplantation receive hydroxyurea and cytarabine or high-dose chemotherapy with autologous stem cell rescue followed by interferon- or imatinib mesylate-based therapy.

Patients over 45 years of age are further randomized to receive an age-adjusted standard conditioning regimen or reduced intensity preparative regimen (mini transplantation) prior to allogeneic transplantation.

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

Trial Contact Information

Trial Lead Organizations

III Medizinische Klinik Mannheim

Ruediger Hehlmann, MD, Protocol chair		Ph: 49-621-383-4115 Email: Ruediger.Hehlmann@med3.ma.uni-heidelberg.de

Germany
	Aachen
	Krankenhaus / Klinikum Krefeld
		Michaela Johnen, MD	Ph:  49-241-736-08
	Aurich
	Kreiskrankenhaus Aurich
		Langer, MD	Ph:  49-4941-94-5000
			Email: langer@kkh-aurich.de
	Bad Hersfeld
	Kreiskrankenhaus
		P J Majunke, MD	Ph:  49-6621-881779
	Berlin
	Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie
		Friedrich Ludwig, MD	Ph:  49-30-757-047-20
			Email: onkopraxis-lmu@GMX.de
	Haematologisch-Onkologische Schwerpunktpraxis
		Ilona Blau, MD	Ph:  49-30-461-4857
	Schwerpunktpraxis fuer Haematologie und Internistische Onkologie
		Christian Sperling, MD	Ph:  49-30-2804-1960
	St. Hedwig Krankenhaus
		Christian Boewer, MD	Ph:  49-30-2311-2255
	Bielefeld
	Onkologische Schwerpunktpraxis Bielefeld
		Marianne Just, MD	Ph:  49-521-137-930
	Bonn
	Augustinum
		Karl Grips, MD	Ph:  49-228-67-38-00
	Brandenburg
	Hamatologische Sprechstunde
		Fischer-Lampsatis, MD	Ph:  49-3381-411-555
	Bremen
	Praxis Dres. F.& G. Doering
		Gabriele Doering, MD	Ph:  49-421-498-5068
	Delmenhorst
	Staedtisches Kliniken Delmenhorst
		Funke, MD	Ph:  49-4221-994-101
	Essen
	Evangelisches Krankenhaus Essen Werden
		Franz-Karl Baur, MD	Ph:  49-201-4089-2099
	Universitaetsklinikum Essen
		Ulrich Duehrsen	Ph:  49-201-723-2417
	Frankfurt
	Klinikum der J.W. Goethe Universitaet
		Dieter Hoelzer, MD, PhD	Ph:  49-69-6301-5194
	Germering
	Internistische Praxisgemeinschaft
		Johann Mittermueller, MD	Ph:  49-89-842-910
	Goslar
	DR Herbert - Nieper Krankenhaus Goslar
		Andreas Hoyer, MD	Ph:  49-5321-555-401
	Gottingen
	Universitaetsklinikum Goettingen
		Claudia Binder, MD, PhD	Ph:  49-551-39-2331
	Hagen
	St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH
		Hartmut Eimermacher, MD	Ph:  49-2331-129-250
	Hamburg
	Asklepios Klinik St. Georg
		Rutjes, MD	Ph:  49-40-2890-2416
	University Medical Center Hamburg - Eppendorf
		Maike de Wit, MD, PhD	Ph:  49-404-2803-4315
		Peter Mundhenk, MD	Ph:  49-40-42803-9073
	Hamm
	Evangelische Krankenhaus Hamm
		Leopold Balleisen, MD	Ph:  49-2381-589-1333
			Email: LBalleisen@evkhamm.de
	Heidelberg
	Medizinische Universitaetsklinik und Poliklinik
		Anthony Ho, MD, PhD	Ph:  49-6221-56-8001
			Email: anthony_ho@med.uni-heidelberg.de
	Ruprecht - Karls - Universitaet Heidelberg
		Stefan Fruehauf, MD	Ph:  49-622-156-8085
	Universitatsklinikum Heidelberg
		Elke Brants	Ph:  49-6221-56-8006
	Homburg
	Medical University Hospital Homburg
		Hans Pees, MD	Ph:  49-6841-162-3000
	Universitaetsklinikum des Saarlandes
		Michael Pfreundschuh, MD	Ph:  49-6841-162-3084
			Email: michael.pfreundschuh@uniklinik-saarland.de
	Kaiserslautern
	Westpfalz-Klinikum GmbH
		Katja Buhl	Ph:  49-631-203-1872
	Karlsruhe
	St. Vincentius - Kliniken
		Gerhard Goeckel, MD	Ph:  49-721-8108-3035
			Email: gerhard.goeckel@vincentius-ka.de
		J. Mezger, MD	Ph:  49-721-8108-3014
	Staedtisches Klinikum Karlsruhe gGmbH
		Contact Person	Ph:  49-721-974-1390
	Kempten
	Klinikum Kempten Oberallgaeu
		Gatter, MD	Ph:  49-831-530-2226
	Kiel
	University Hospital Schleswig-Holstein - Kiel Campus
		Robert Schoch, MD	Ph:  49-431-1697-5226
	Krefeld
	Klinikum Krefeld GmbH
		Sabine Helmer, MD	Ph:  49-2151-32-2709
	Langen
	Internistisches Fachaerzte Zentrum Langen
		Andreas Koehler, MD	Ph:  49-61-032-8787
	Lebach
	Caritas - Krakenhaus Lebach
		Harald Jost, MD	Ph:  49-6881-501-273
	Leer
	Onkologische Schwerpunktpraxis - Leer
		Lothar Mueller, MD	Ph:  49-491-987-910
			Email: Lothar.Mueller@onkologie-leer.de
	Lemgo
	Klinikum Lippe - Lemgo
		Contact Person	Ph:  49-52-6126-4123
	Ludwigshafen am Rhein
	Klinikum der Stadt Ludwigshafen am Rhein
		Henrich, MD	Ph:  49-621-503-3900
			Email: henrichd@klilu.de
	Mannheim
	III Medizinische Klinik Mannheim
		Michael Schatz, MD	Ph:  49-621-383-4114
	Monchengladbach
	Hospital Maria-Hilf II
		Lange, MD	Ph:  49-2161-892-2212
	Muenchen
	Krankenhaus Muenchen Schwabing
		Christof Fischer, MD	Ph:  49-89-3068-2389
	Muenster
	Haematologisch - Onkologische Gemeinschaftspraxis - Muenster
		Juergen Wehmeyer, MD	Ph:  49-251-620-080
			Email: wehmeyer@onkologie-muenster.de
	Munich
	Haematologische Schwerpunktpraxis
		Helmut Hitz, MD	Ph:  49-89-9972-0275
	Klinikum der Universitaet Muenchen - Grosshadern Campus
		Torsten Haferlach, MD	Ph:  49-89-7095-4970
	Regensburg
	Hematologische Onkologische Praxis
		Robert Dengler, MD	Ph:  49-941-566-342
			Email: robert.dougler@t-online.de
	Klinikum der Universitaet Regensburg
		Stefan Krause, MD	Ph:  49-941-944-5538
	Remscheid
	Klinikum Remscheid GmbH
		Arthur Wehmeier, MD	Ph:  49-21-9113-4700
		F. Meierkord, MD	Ph:  49-2191-13-3983
	Russelsheim
	Internistische Schwerpunktpraxis
		M. Baldus, MD	Ph:  49-6142-940-321
	Schwaebisch Hall
	Diakonie - Krankenhaus
		Thomas Geer, MD	Ph:  49-791-753-4411
			Email: tgeer@diaksha.de
	Siegen
	Kreiskrankenhaus Siegen
		Schulz, MD	Ph:  49-271-705-0
	St. Marien - Krankenhaus Siegen GMBH
		Winfried Gassmann, MD	Ph:  0271 231 2260
	Stralsund
	Hanse-Klinikum Stralsund - Krankenhaus West
		Thomas Heinz Ittel, MD	Ph:  49-3831-35-2700
			Email: medizinische.klinik@klinikum-stralsund.de
	Straubing
	Onkologische Schwerpunktpraxis - Straubing
		Matthias Demandt, MD	Ph:  49-9421-90777
	Stuttgart
	Diakonie Klinikum Stuttgart
		Else Heidemann, MD	Ph:  49-711-991-3501
	Haematologische Praxis
		Gregor Springer, MD	Ph:  49-711-222-0244
	Klinik fuer Onkologie - Katharinenhospital Stuttgart
		Hans-Guenther Mergenthaler, MD	Ph:  49-711-278-5601
			Email: h.mergenthaler@katharinehospital.de
	Robert-Bosch-Krankenhaus
		Walter Aulitzky, MD	Ph:  49-711-8101-3506
			Email: walter.aulitzky@rbk.de
	Trier
		Bernhard Rendenbach, MD	Ph:  49-651-493-93
			Email: info@straurenlau.de
	Tuebingen
	Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie
		Swen Jacki, MD	Ph:  49-7071-567-888
	Southwest German Cancer Center at Eberhard-Karls-University
		Tim Henrik Brummendorf, MD	Ph:  49-7071-298-0648
			Email: tim.bruemmendorf@med.uni-tuebingen.de
	Weiden
	Haematologische Praxis
		Johann Weiss, MD	Ph:  49-961-320-60
	Wuppertal
	Helios Kliniken Wuppertal University Hospital
		Aruna Raghavachar, MD, PhD	Ph:  49-202-896-3351
			Email: araghavachar@wuppertal.helios-kliniken.de
	Praxis Fuer Haemotologie Und Internistischer Onkologie
		Werner Fett, MD	Ph:  49-202-449-232
			Email: fett-onkologe@t-online.de
	Wurzburg
	Hamatologisch - Onkologische Praxis Wurzburg
		Rudolf Schlag, MD	Ph:  49-931-322-670
	University Wurzburg
		M. Goebeler, MD	Ph:  49-931-201-7080
Switzerland
	Basel
		Walter Weber-Stadelmann, MD	Ph:  41-61-261-0225
			Email: cancer@bluewin.ch

Registry Information
Official Title		Treatment Optimization Trial in Chronic Myeloid Leukemia (CML) - Randomized Controlled Comparison of Imatinib vs. Imatinib/Interferon-alpha vs. Imatinib/Low-Dose AraC vs. Interferon-alpha Standard Therapy and Determination of the Role of Allografting in Newly Diagnosed Chronic Phase
Trial Start Date		2002-06-28
Trial Completion Date		2016-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00055874
Date Submitted to PDQ		2003-01-22
Information Last Verified		2006-11-27