A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age

British Journal of Haematology

Volumn 170, Issue 3, 2015, Pages 349-355

  Buckley, Sarah A ^a,b   Mawad, Raya ^a,b   Gooley, Ted A ^a,b   Becker, Pamela S ^a,b   Sandhu, Vicky ^a   Hendrie, Paul ^a,b   Scott, Bart L ^a,b   Wood, Brent L ^a,b   Walter, Roland B ^a,b   Smith, Kelly ^a,b   Dean, Carol ^a   Estey, Elihu H ^a,b   Pagel, John M ^a,b  

^a Fred Hutchinson Cancer Research Center   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

acute myeloid leukaemia; clofarabine; elderly; myelodysplastic syndrome; phase I II

Indexed keywords

CLOFARABINE; CYTARABINE; ADENINE NUCLEOTIDE; ANTINEOPLASTIC AGENT; ARABINONUCLEOSIDE;

ACUTE MYELOBLASTIC LEUKEMIA; ADULT; AGED; ARTICLE; ATHEROSCLEROSIS; BACTEREMIA; BACTERIAL INFECTION; BLOOD TOXICITY; BLOODSTREAM INFECTION; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CANCER SURVIVAL; CEREBROVASCULAR ACCIDENT; CLINICAL ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE FREE SURVIVAL; DISEASE SEVERITY; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; ELECTROLYTE DISTURBANCE; FAINTNESS; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; GASTROINTESTINAL HEMORRHAGE; HEART ARRHYTHMIA; HEART FAILURE; HIGH RISK PATIENT; HOSPITALIZATION; HUMAN; LOW DRUG DOSE; MALE; MAXIMUM TOLERATED DOSE; MENTAL DISEASE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MYCOSIS; MYELODYSPLASTIC SYNDROME; OUTCOME ASSESSMENT; OUTPATIENT DEPARTMENT; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; SALVAGE THERAPY; SEPSIS; SURVIVAL RATE; SURVIVAL TIME; CLINICAL TRIAL; LEUKEMIA, MYELOID, ACUTE; MIDDLE AGED; MORTALITY; MYELODYSPLASTIC SYNDROMES; RISK FACTOR; VERY ELDERLY;

ADENINE NUCLEOTIDES; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ARABINONUCLEOSIDES; CYTARABINE; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; RISK FACTORS; SURVIVAL RATE;

EID: 84942083402     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.13437     Document Type: Article

References (14)

1. Appelbaum, F.R., Gundacker, H., Head, D.R., Slovak, M.L., Willman, C.L., Godwin, J.E., Anderson, J.E. & Petersdorf, S.H. (2006) Age and acute myeloid leukemia. Blood, 107, 3481–3485.
2. Burnett, A.K., Russell, N.H., Hunter, A.E., Milligan, D., Knapper, S., Wheatley, K., Yin, J., McMullin, M.F., Ali, S., Bowen, D. & Hills, R.K.; UK National Cancer Research Institute AML Working Group. (2013) Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood, 122, 1384–1394.
3. Doubek, M., Palasek, I., Brychtova, Y., Buchtova, I. & Mayer, J. (2005) Acute myeloid leukemia treatment in patients over 60 years of age. Comparison of symptomatic, palliative, and aggressive therapy. Neoplasma, 52, 411–414.
4. Faderl, S., Gandhi, V., O'Brien, S., Bonate, P., Cortes, J., Estey, E., Berna, M., Wierda, W., Garcia-Manero, G., Ferrajoli, A., Estrov, Z., Giles, F.J., Du, M., Kwari, M., Keating, M., Plunkett, W. & Kantarjian, H. (2005) Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood, 105, 940–947.
5. Faderl, S., Ravandi, F., Huang, X., Garcia-Manero, G., Ferrajoli, A., Estrov, Z., Borthakur, G., Verstovsek, S., Thomas, D.A., Kwari, M. & Kantarjian, H.M. (2008) A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood, 112, 1638–1645.
6. Faderl, S., Garcia-Manero, G., Estrov, Z., Ravandi, F., Borthakur, G., Cortes, J.E., O'Brien, S., Gandhi, V., Plunkett, W., Byrd, A., Kwari, M. & Kantarjian, H.M. (2010) Oral clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome. Journal of Clinical Oncology, 28, 2755–2760.
7. Genini, D., Adachi, S., Chao, Q., Rose, D.W., Carrera, C.J., Cottam, H.B., Carson, D.A. & Leoni, L.M. (2000) Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria. Blood, 96, 3537–3543.
8. Grimwade, D., Hills, R.K., Moorman, A.V., Walker, H., Chatters, S., Goldstone, A.H., Wheatley, K., Harrison, C.J. & Burnett, A.K.; National Cancer Research Institute Adult Leukaemia Working Group. (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood, 116, 354–365.
9. Kantarjian, H.M., Erba, H.P., Claxton, D., Arellano, M., Lyons, R.M., Kovascovics, T., Gabrilove, J., Craig, M., Douer, D., Maris, M., Petersdorf, S., Shami, P.J., Yeager, A.M., Eckert, S., Abichandani, R. & Faderl, S. (2010) Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. Journal of Clinical Oncology, 28, 549–555.
10. Löwenberg, B., Zittoun, R., Kerkhofs, H., Jehn, U., Abels, J., Debusscher, L., Cauchie, C., Peetermans, M., Solbu, G., Suciu, S. & Stryckmans, P. (1989) On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. Journal of Clinical Oncology, 7, 1268–1274.
11. National Cancer Institute. Surveillance, epidemiology, and end results. SEER stat fact sheets: leukemia. Available: http://seer.cancer.gov/statfacts/html/leuks.html. Accessed 9 December 2014.
12. O'Donnell, M.R., Abboud, C.N., Altman, J., Appelbaum, F.R., Arber, D.A., Attar, E., Borate, U., Coutre, S.E., Damon, L.E., Goorha, S., Lancet, J., Maness, L.J., Marcucci, G., Millenson, M.M., Moore, J.O., Ravandi, F., Shami, P.J., Smith, B.D., Stone, R.M., Strickland, S.A., Tallman, M.S., Wang, E.S., Naganuma, M. & Gregory, K.M. (2012) Acute myeloid leukemia. Journal of the National Comprehensive Cancer Network, 10, 984–1021.
13. Reichelova, V., Liliemark, J. & Albertioni, F. (1995) Liquid chromatographic study of acid stability of 2-chloro-2′-arabino-fluoro-2′-deoxyadenosine, 2-chloro-2′-deoxyadenosine and related analogues. Journal of Pharmaceutical and Biomedical Analysis, 13, 711–714.
14. Walter, R.B., Othus, M., Borthakur, G., Ravandi, F., Cortes, J.E., Pierce, S.A., Appelbaum, F.R., Kantarjian, H.A. & Estey, E.H. (2011) Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. Journal of Clinical Oncology, 29, 4417–4423.