Clinical trial NCT01059734: S9031-S9126-S9333-S9500-B Biomarker Expression in Patients With Acute Myeloid Leukemia
Official title: Topoisomerase 2 Expression and Acute Myeloid Leukemia (AML)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Leukemia
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with del(5q)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
secondary acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute megakaryoblastic leukemia (M7)
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-02-01
Enrollment: 357
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients enrolled on S0931, S9126, S9333 or S9500 consenting to use of specimens for future research

Brief summary: RATIONALE: Studying samples of bone marrow from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This research study is looking at biomarker expression in bone marrow samples from patients with acute myeloid leukemia.

Detailed description: OBJECTIVES:

* Estimate the distributions of topoisomerase 2 (TOP2) expression and single nucleotide polymorphisms (SNPs) in patients with newly diagnosed acute myeloid leukemia (AML).
* Estimate the distributions of mutations in TOP2 phosphorylation sites (by SNP analysis) in these patients.
* Investigate whether expression of TOP2 or mutations in TOP2 phosphorylation sites vary with patient or disease characteristics in these patients.
* Test whether TOP2 expression correlates with complete remission rates, relapse-free survival, and overall survival of these patients.
* Conduct preliminary analyses to estimate the distributions of TOP2 expression and mutations in TOP2 phosphorylation sites (by SNP analysis) in patients with relapsed and/or refractory AML.
* Investigate whether expression of TOP2 and mutations in TOP2 phosphorylation sites vary with patient or disease characteristics in patients with relapsed and/or refractory AML.
* Test whether TOP2 expression and mutations in TOP2 phosphorylation sites differ between previously untreated and relapsed/refractory AML patients.

OUTLINE: This is a multicenter study.

Archived RNA specimens are analyzed for topoisomerase 2 transcriptional expression by quantitative real-time polymerase chain reaction (PCR) and for mutations within TOP2 phosphorylation sites by single nucleotide polymorphism analysis.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of acute myeloid leukemia

  * All subtypes allowed (except acute promyelocytic leukemia \[M3\])
  * Previously untreated OR relapsed/refractory disease
* Isolated RNA specimens from bone marrow aspirate samples available from patients who participated on SWOG-9031, SWOG-9333 (cytarabine/daunorubicin hydrochloride induction arm only), SWOG-9500, or SWOG-9126

PATIENT CHARACTERISTICS:

* Not specified

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Distribution of topoisomerase 2 (TOP2) expression and single nucleotide polymorphisms
timeFrame: immediate
measure: Distributions of mutations in TOP2 phosphorylation sites
timeFrame: immediate
measure: Correlation of TOP2 expression with complete remission rates, relapse-free survival, and overall survival
timeFrame: immediate
measure: Variation of TOP2 expression and mutations in TOP2 phosphorylation sites among patients and disease characteristics
timeFrame: immediate
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: The Cleveland Clinic
name: Anjali Advani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Medeiros BC, Othus M, Fang M, Appelbaum FR, Erba HP. Cytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia. Haematologica. 2015 Mar;100(3):331-5. doi: 10.3324/haematol.2014.117267. Epub 2014 Dec 19.
citation: Medeiros BC, Othus M, Estey EH, Fang M, Appelbaum FR. Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia. Br J Haematol. 2014 Jan;164(2):245-50. doi: 10.1111/bjh.12625. Epub 2013 Oct 28.