Evidence map›Paper›PMID 26553781›Full record

ArticleJournal of the National Cancer Institute2016

Phase I Clinical Trials in Acute Myeloid Leukemia: 23-Year Experience From Cancer Therapy Evaluation Program of the National Cancer Institute.

Joshua F Zeidner, Judith E Karp, Amanda L Blackford, Matthew C Foster, E Claire Dees, Gary Smith, S Percy Ivy, Pamela Harris

Abstract read

PubMed Full text at PMC Publisher

In one paragraph

Article in Journal of the National Cancer Institute, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it

0cells of the map it votes in

4citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

Targeting the Epigenetic-Immune Axis in Acute Myeloid Leukemia: Current Advances and Future Directions.Current oncology reports · 2026
Review
Recent Developments and Future Perspectives of Purine Derivatives as a Promising Scaffold in Drug Discovery.Current topics in medicinal chemistry · 2024
Review
Design, Synthesis, In Silico Studies and Inhibitory Activity towards Bcr-Abl, BTK and FLT3-ITD of New 2,6,9-Trisubstituted Purine Derivatives as Potential Agents for the Treatment of Leukaemia.Pharmaceutics · 2022
Article
Trends in Grade 5 Toxicity and Response in Phase I Trials in Hematologic Malignancy: 20-Year Experience From the Cancer Therapy Evaluation Program at the National Cancer Institute.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Joshua F ZeidnerAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

Judith E KarpAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

Amanda L BlackfordAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

Matthew C FosterAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

E Claire DeesAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

Gary SmithAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

S Percy IvyAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

Pamela HarrisAffiliations of authors: University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC (JFZ, MCF, ECD); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center , Baltimore, MD (JEK, ALB); Cancer Therapy Evaluation Program , National Cancer Institute , Rockville, MD (GS, SPI, PH) .

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026

$201.5M

NCI NIH HHS P30 CA016086

6 · The paper itself

Abstract

backgroundTherapy 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.

methodsA 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.

resultsThere 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).

conclusionsThere 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.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsClinical Trials, Phase I as TopicFemaleHumansLeukemia, Myeloid, AcuteMaleMiddle AgedNational Cancer Institute (U.S.)Odds RatioPatient SelectionRetrospective StudiesSurvival AnalysisTreatment OutcomeAntineoplastic Agents

Identifiers

PMID26553781

DOI10.1093/jnci/djv335

PMCPMC4668761

What OpenQuestion holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.