Imatinib Mesylate and Cytarabine in Treating Patients With Newly Diagnosed Chronic Myeloid Leukemia
A Dose-ranging Phase I/II Study of STI571 in Combination With Cytarabin in Patients With First Chronic Phase Chronic Myeloid Leukemia
RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate and chemotherapy may kill more cancer cells.
PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate plus cytarabine in treating patients who have newly diagnosed chronic myeloid leukemia.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
OBJECTIVES:
- Determine the maximum tolerated dose of imatinib mesylate and cytarabine in patients with newly diagnosed chronic phase chronic myeloid leukemia.
- Determine the feasibility of this regimen as defined by dose-limiting toxicity of this regimen and treatment-related mortality in no more than 5% of these patients.
- Determine the rate and duration of molecular response, complete hematological response, and complete cytogenetic response in patients treated with this regimen.
- Determine the time to treatment failure of patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of imatinib mesylate and cytarabine.
Patients receive oral imatinib mesylate alone once daily on days 1-21. Patients then receive oral imatinib mesylate once daily and cytarabine IV over 1-3 hours on days 1-7. Combination therapy repeats every 28-42 days for 2 courses. Patients then receive maintenance oral imatinib mesylate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 5-20 patients receive escalating doses of imatinib mesylate and cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 5/5, 5/10, or 5/20 patients experience dose-limiting toxicity.
Patients are followed every 6 months.
PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 2 years.
Tipo di studio
Iscrizione (Anticipato)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
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Brugge, Belgio, 8000
- AZ Sint-Jan
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Brussels, Belgio, 1200
- Cliniques Universitaires Saint-Luc
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Brussels, Belgio, 1000
- Institut Jules Bordet
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Leuven, Belgio, B-3000
- U.Z. Gasthuisberg
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Mont-Godinne Yvoir, Belgio, 5530
- Clinique Universitaire De Mont-Godinne
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's-Gravenhage, Olanda, 2545 CH
- HagaZiekenhuis - Locatie Leyenburg
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Amersfoort, Olanda, 3816 CP
- Meander Medisch Centrum
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Amsterdam, Olanda, 1105 AZ
- Academisch Medisch Centrum at University of Amsterdam
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Amsterdam, Olanda, 10P 1HV
- Vrije Universiteit Medisch Centrum
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Enschede, Olanda, 7500 KA
- Medisch Spectrum Twente
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Groningen, Olanda, 9713 EZ
- University Medical Center Groningen
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Leiden, Olanda, 2300 RC
- Leiden University Medical Center
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Nijmegen, Olanda, 6500 HB
- Universitair Medisch Centrum St. Radboud - Nijmegen
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Rotterdam, Olanda, 3008 AE
- Daniel Den Hoed Cancer Center at Erasmus Medical Center
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Utrecht, Olanda, 3584 CX
- University Medical Center Utrecht
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Zwolle, Olanda, 8000 GK
- Isala Klinieken - locatie Sophia
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
DISEASE CHARACTERISTICS:
Newly diagnosed chronic myeloid leukemia in first chronic phase (within the past 6 months)
- Philadelphia-chromosome positive OR
- bcr-abl rearrangement
- No prior treatment within the past 6 months other than hydroxyurea
PATIENT CHARACTERISTICS:
Age:
- 18 to 65
Performance status:
- WHO 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- No hepatic dysfunction
- Bilirubin less than 2 times normal
- ALT less than 4 times normal
Renal:
- No renal dysfunction
- Creatinine less than 2.3 mg/dL
Cardiovascular:
- No severe cardiac dysfunction
- No New York Heart Association class II-IV heart disease
Pulmonary:
- No severe pulmonary disease
Other:
- HIV negative
- No severe neurologic disease
- No active uncontrolled infection
- No other active malignancy within the past 5 years except basal cell skin cancer or stage 0 cervical cancer
- Not pregnant or nursing
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- No concurrent allogeneic transplantation with an HLA-A, B, DR-matched sibling donor or matched-unrelated donor
Chemotherapy:
- See Disease Characteristics
Endocrine therapy:
- See Disease Characteristics
Radiotherapy:
- See Disease Characteristics
Surgery:
- See Disease Characteristics
Other:
- No concurrent grapefruit or grapefruit juice
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
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Incidence of dose-limiting toxicity and treatment-related toxicity per dose level
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Misure di risultato secondarie
Misura del risultato |
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Tempo al fallimento del trattamento
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Sopravvivenza globale
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Rate and duration of molecular response
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Rate and duration of complete hematological response
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Rate and duration of complete cytogenetic response
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Collaboratori e investigatori
Investigatori
- Cattedra di studio: J.J. Cornelissen, MD, Daniel Den Hoed Cancer Center at Erasmus Medical Center
Pubblicazioni e link utili
Pubblicazioni generali
- Deenik W, Janssen JJ, van der Holt B, Verhoef GE, Smit WM, Kersten MJ, Daenen SM, Verdonck LF, Ferrant A, Schattenberg AV, Sonneveld P, van Marwijk Kooy M, Wittebol S, Willemze R, Wijermans PW, Beverloo HB, Lowenberg B, Valk PJ, Ossenkoppele GJ, Cornelissen JJ. Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia. Haematologica. 2010 Jun;95(6):914-21. doi: 10.3324/haematol.2009.016766. Epub 2009 Dec 16.
- Deenik W, van der Holt B, Verhoef GE, Smit WM, Kersten MJ, Kluin-Nelemans HC, Verdonck LF, Ferrant A, Schattenberg AV, Janssen JJ, Sonneveld P, van Marwijk Kooy M, Wittebol S, Willemze R, Wijermans PW, Westveer PH, Beverloo HB, Valk P, Lowenberg B, Ossenkoppele GJ, Cornelissen JJ. Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia. Blood. 2008 Mar 1;111(5):2581-8. doi: 10.1182/blood-2007-08-107482. Epub 2008 Jan 2.
- Thielen N, van der Holt B, Cornelissen JJ, Verhoef GE, Gussinklo T, Biemond BJ, Daenen SM, Deenik W, van Marwijk Kooy R, Petersen E, Smit WM, Valk PJ, Ossenkoppele GJ, Janssen JJ. Imatinib discontinuation in chronic phase myeloid leukaemia patients in sustained complete molecular response: a randomised trial of the Dutch-Belgian Cooperative Trial for Haemato-Oncology (HOVON). Eur J Cancer. 2013 Oct;49(15):3242-6. doi: 10.1016/j.ejca.2013.06.018. Epub 2013 Jul 19.
Studiare le date dei record
Studia le date principali
Inizio studio
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie per tipo istologico
- Neoplasie
- Malattie del midollo osseo
- Malattie ematologiche
- Malattie mieloproliferative
- Leucemia, mieloide
- Leucemia
- Leucemia, Mielogena, Cronica, BCR-ABL Positivo
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti antivirali
- Inibitori enzimatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Inibitori della chinasi proteica
- Citarabina
- Imatinib mesilato
Altri numeri di identificazione dello studio
- CDR0000069141
- CKTO-2001-03
- HOVON-51CML
- EU-20132
- HOVON-CKTO-2001-03
- NOVARTIS-CST1571ANL01
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