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Annals of Hematology

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01.04.2004 | Ongoing Clinical Studies

Imatinib and beyond—the new CML study IV

A randomized controlled comparison of imatinib vs imatinib/interferon-alpha vs imatinib/low-dose AraC vs imatinib after interferon-alpha failure in newly diagnosed chronic phase chronic myeloid leukemia

verfasst von: U. Berger, G. Engelich, A. Reiter, A. Hochhaus, R. Hehlmann, The German CML Study Group

Erschienen in: Annals of Hematology | Ausgabe 4/2004

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Table 1

Synopsis of CML-study IV
Objectives	1. Primary imatinib-based vs imatinib after interferon-alpha (IFN) failure
	2. Imatinib vs imatinib/IFN vs imatinib/low-dose AraC
	3. Allografting vs imatinib-based therapy in patients eligible for transplantation
	4. Age-adjusted standard intensity vs reduced intensity conditioning in patients older than 45 years of age
	Additional objectives:
	1. Time of first appearance and duration of hematologic, cytogenetic, and molecular responses
	2. Correlation of quality of responses with survival
	3. Comparison of short- and long-term adverse effects of imatinib-based mono- and combination therapies and of imatinib after IFN failure
	4. Duration of blastic phase and immunophenotype of blasts in dependence of treatment
	5. Survival and outcome of high-risk patients (new CML score) after early allografting
	6. Hematologic, cytogenetic, and molecular responses of imatinib as salvage therapy after IFN failure
	7. Validation of the new CML score or development of a new prognostic score adapted for imatinib-based therapies
	8. Impact of normal or subnormal WBC counts during the course of treatment for the duration of chronic phase and effect on survival
	9. Novel treatment approaches for refractory CML
	10. Influence of pretransplant therapies on the outcome of allografting
	11. Analysis of complete cytogenetic responders within the different treatment groups
Study endpoints	Primary: overall survival, time to progression, risk group-dependent survival, hematologic, cytogenetic, and molecular response
Study endpoints	Secondary: toxicity, quality of life
Trial design	Randomization into four treatment strategies: imatinib, imatinib/IFN, imatinib/low-dose AraC, or imatinib after failure of IFN ± hydroxyurea (HU) (± low-dose AraC)
Trial design	High risk patients who do not profit from primary IFN will be randomized instead to receive primary imatinib 800 mg
Study period	July 2002 until 2012
Sample size	Total number of subjects to be enrolled n=1600
Inclusion criteria	Newly diagnosed BCR-ABL positive CML in chronic phase
	Pretreatment with HU or anagrelide is permitted
	No age limit
	Informed consent
Exclusion criteria	Pretreatment with chemotherapy, IFN, or irradiation
	Second malignancy, if it requires therapy and the estimated life expectancy is shorter than the median survival of CML
	Other serious diseases, pregnancy including lactation period, or other conditions which could prevent the required protocol-compliance
	Participation in another trial
	No informed consent
Treatment plan	Arm I: 400 mg (dose increased to 600 mg up to 800 mg, if no hematologic response after 2 or 6 months) imatinib p.o. qd.
	Arm II: 400 mg (dose increased to 600 mg up to 800 mg, if no hematologic response after 2 or 6 months) imatinib p.o. qd + IFN, initially 1.5–3.0×10⁶ IU flat dose s.c. qd, later IFN dose to be adjusted according to WBC and tolerability
	Arm III: 400 mg (dose increased to 600 mg up to 800 mg, if no hematologic response after 2 or 6 months) imatinib p.o. qd + low-dose AraC, initially 10 mg flat dose up to 2×5 days/month, starting after 3 months, later AraC dose to be adjusted according to WBC and tolerability
	Arm IV: IFN, initially 3×10⁶ IU s.c. qd, later IFN dose increase made according to CBC and attainment of hematologic response. Imatinib, 400 mg p.o. qd after IFN failure. High risk: primary imatinib 800 mg p.o. qd.
	Patients eligible for allogeneic SCT who failed imatinib are randomized genetically by the availability of a HLA-identical related or unrelated donor to undergo allografting or to continue any form of salvage therapy
	Patients older than 45 years of age will be further randomized to receive an age-adjusted standard conditioning regimen or reduced-intensity preparative regimen

…

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Titel: Imatinib and beyond—the new CML study IV
A randomized controlled comparison of imatinib vs imatinib/interferon-alpha vs imatinib/low-dose AraC vs imatinib after interferon-alpha failure in newly diagnosed chronic phase chronic myeloid leukemia
verfasst von: U. Berger
G. Engelich
A. Reiter
A. Hochhaus
R. Hehlmann
The German CML Study Group
Publikationsdatum: 01.04.2004
Verlag: Springer-Verlag
Erschienen in: Annals of Hematology / Ausgabe 4/2004
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-003-0807-x

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