TY - JOUR
T1 - Phase i Clinical Trials in Acute Myeloid Leukemia
T2 - 23-Year Experience from Cancer Therapy Evaluation Program of the National Cancer Institute
AU - Zeidner, Joshua F.
AU - Karp, Judith E.
AU - Blackford, Amanda L.
AU - Foster, Matthew C.
AU - Dees, E. Claire
AU - Smith, Gary
AU - Ivy, S. Percy
AU - Harris, Pamela
N1 - Funding Information:
This work was supported by the National Cancer Institute. JFZ received a 2013 Conquer Cancer Foundation Young Investigator Award, in memory of Dr. John R. Durant, and is a 2014 to 2017 Leukemia and Lymphoma Society Special Fellow in Clinical Research.
Publisher Copyright:
© 2015 The Author 2015. Published by Oxford University Press. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Background: Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time. Methods: A retrospective analysis was performed on 711 adult AML patients enrolling in 45 phase I clinical trials supported by the Cancer Therapy Evaluation Program of the National Cancer Institute from 1986 to 2009. Changes in ORR and mortality rates for patients enrolled in 1986 to 1990, 1991 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009 were estimated with multivariable logistic regression models. All statistical tests were two-sided. Results: There was a statistically significant increase in AML patients enrolling in phase I clinical trials over time (1986 to 1990: n = 61; 2006 to 2009: n = 256; P =. 03). The ORR for the entire cohort was 15.4% (1986 to 1990: 8.9%, 1991 to 1995: 21.1%; 1996 to 2000: 7.0%; 2001 to 2005: 10.0%; 2006 to 2009: 22.6%), and it statistically significantly improved over time (P <. 001). There was a statistically significant improvement in ORRs with novel agents in combination vs single agents (ORR = 22.8% vs 4.7%, respectively, odds ratio = 5.95, 95% confidence interval = 3.22 to 11.9, P <. 001). The 60-day mortality rate for the entire cohort was 22.6%, but it statistically significantly improved over time (P =. 009). Conclusions: There has been an encouraging increase in AML patients enrolling in phase I clinical studies over time. The improvement in ORRs appears to be partly because of the increase in combination trials and the inclusion of previously untreated poor-risk AML. Continued enrollment of AML patients in early phase clinical trials is vital for drug development and improvement in therapeutic outcomes.
AB - Background: Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time. Methods: A retrospective analysis was performed on 711 adult AML patients enrolling in 45 phase I clinical trials supported by the Cancer Therapy Evaluation Program of the National Cancer Institute from 1986 to 2009. Changes in ORR and mortality rates for patients enrolled in 1986 to 1990, 1991 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009 were estimated with multivariable logistic regression models. All statistical tests were two-sided. Results: There was a statistically significant increase in AML patients enrolling in phase I clinical trials over time (1986 to 1990: n = 61; 2006 to 2009: n = 256; P =. 03). The ORR for the entire cohort was 15.4% (1986 to 1990: 8.9%, 1991 to 1995: 21.1%; 1996 to 2000: 7.0%; 2001 to 2005: 10.0%; 2006 to 2009: 22.6%), and it statistically significantly improved over time (P <. 001). There was a statistically significant improvement in ORRs with novel agents in combination vs single agents (ORR = 22.8% vs 4.7%, respectively, odds ratio = 5.95, 95% confidence interval = 3.22 to 11.9, P <. 001). The 60-day mortality rate for the entire cohort was 22.6%, but it statistically significantly improved over time (P =. 009). Conclusions: There has been an encouraging increase in AML patients enrolling in phase I clinical studies over time. The improvement in ORRs appears to be partly because of the increase in combination trials and the inclusion of previously untreated poor-risk AML. Continued enrollment of AML patients in early phase clinical trials is vital for drug development and improvement in therapeutic outcomes.
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U2 - 10.1093/jnci/djv335
DO - 10.1093/jnci/djv335
M3 - Article
C2 - 26553781
AN - SCOPUS:84962489103
SN - 0027-8874
VL - 108
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 3
M1 - djv335
ER -