Clinical trial NCT00900224: Studying Tissue and Blood Samples From Patients With Acute Myeloid Leukemia
Official title: Assessment of Novel Molecular Markers in Acute Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Leukemia
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
secondary acute myeloid leukemia
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 529
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with acute myeloid leukemia

Brief summary: RATIONALE: Studying samples of tissue and blood 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 tissue and blood samples from patients with acute myeloid leukemia.

Detailed description: OBJECTIVES:

* Prospectively obtain specimens required for diagnostic review and molecular characterization ensuring eligibility for CALGB Leukemia Committee Clinical trials (for clinical trials designed to enroll specific molecular subtypes, results to determine eligibility will be reported to treating physicians no more than 72 hours after specimen receipt at the repository).
* Determine the frequency of specific gene markers (i.e., FLT3 ITD, CBF, MLL PTD, NPM1, KIT, RAS, CEBPA, WT1, JAK2, RUNX1, TET2, CBL, IDH1 and IDH2, ASXL1, mutations, aberrant BAALC, ERG, FLT3, MN1, EVI1, and APP) over-expression and levels of promoter methylation of specific genes (e.g., ESR1, WIT1, P15, MYOD1, ID4, DPK) in defined cytogenetic subgroups of patients with acute myeloid leukemia (AML).
* Correlate these gene markers with clinical and laboratory parameters in these patients.
* Correlate these gene markers with clinical outcome (i.e., complete remission \[CR\], disease-free survival \[DFS\], cumulative incidence of relapse \[CIR\], and overall survival \[OS\]) in these patients.
* Identify specific microarray multi-gene expression signatures in these patients.
* Correlate specific microarray multi-gene expression signatures with clinical and laboratory parameters in these patients.
* Correlate specific microarray multi-gene expression signatures with clinical outcome (i.e., CR, DFS, CIR, and OS) in these patients.
* Identify specific microarray multi-microRNA (miR) expression signatures in these patients
* Correlate specific microarray multi-miR expression signatures with clinical and laboratory parameters in these patients.
* Correlate specific microarray multi-miR expression signatures with clinical outcome (i.e., CR, DFS, CIR, and OS) in these patients.
* Explore the relative contribution of prognostic gene markers (i.e., FLT3 ITD, MLL PTD, NPM1, KIT, RAS, CEBPA, WT1, and JAK2 mutations, and aberrant BAALC, ERG, FLT3, MN1, and EVI1 over-expression), levels of promoter methylation of specific genes (e.g., ESR1, WIT1, P15, MYOD1, ID4, DPK), and microarray gene and miR expression signatures in defined cytogenetic subgroups of AML.
* Determine changes in these molecular markers and microarray gene and miR expression signatures at CR and relapse and the influence that these changes have on subsequent clinical course.
* Correlate the relative level of nuclear pSTAT5 and pERK in bone marrow blasts with outcome (EFS, CR, DFS, OS).

OUTLINE: This is a multicenter study.

Previously procured and archived bone marrow aspirate samples, blood and buccal cell samples, and bone marrow biopsy slides are analyzed for FLT3 ITD, MLL PTD, NPM1, KIT, KRAS, NRAS, CEBPA, WT1, JAK2, RUNX1, TET2, ASXL1, IDH1 and IDH2, and CBL mutations, CBF fusion genes, levels of BAALC, ERG, EVI1, MN1, and APP microarray gene-expression, microRNA gene-expression signature, levels of methylation of genes silenced in AML, and genomic DNA by PCR amplification, RT-PCR, and denaturing high-performance liquid chromatography.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed acute myeloid leukemia (AML)
* Tissue samples from previously untreated patients with AML considered for enrollment onto ongoing and future CALGB treatment protocols
* AML tissue samples from companion Leukemia Tissue Bank protocol CALGB-9665 and the companion cytogenetic protocol CALGB-8461
* AML diagnostic bone marrow and/or blood samples from patients enrolled on CLB-9720, CLB-9621 (all cytogenetic subtypes), and CALGB-19808 (abnormal cytogenetics only)

Primary outcomes:
measure: Presence of molecular markers that fulfill eligibility criteria in diagnostic samples from AML patients considered for CALGB therapeutic protocols
timeFrame: baseline
measure: Frequency of specific single-gene markers over-expression and levels of promoter methylation of specific genes
timeFrame: baseline
measure: Predictive value of specific single-gene markers
timeFrame: baseline
measure: Microarray multi-gene and multi-miR expression signatures
timeFrame: baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Mountain View
country: United States
facility: Camino Medical Group - Treatment Center
state: California
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Bloomington
country: United States
facility: Illinois CancerCare - Bloomington
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare - Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare - Carthage
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare - Eureka
state: Illinois
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Havana
country: United States
facility: Illinois CancerCare - Havana
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare - Kewanee Clinic
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare - Macomb
state: Illinois
city: Monmouth
country: United States
facility: Illinois CancerCare - Monmouth
state: Illinois
city: Monmouth
country: United States
facility: OSF Holy Family Medical Center
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Normal
country: United States
facility: Illinois CancerCare - Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare - Pekin
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare - Peru
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare - Princeton
state: Illinois
city: Spring Valley
country: United States
facility: Illinois CancerCare - Spring Valley
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Augusta
country: United States
facility: Harold Alfond Center for Cancer Care
state: Maine
city: Bangor
country: United States
facility: CancerCare of Maine at Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
state: Massachusetts
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Muskegon
country: United States
facility: Mercy General Health Partners
state: Michigan
city: Reed City
country: United States
facility: Spectrum Health Reed City Hospital
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: Monter Cancer Center of the North Shore-LIJ Health System
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: Don Monti Comprehensive Cancer Center at North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center at ECU Medical School
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Clara Bloomfield, MD
role: STUDY_CHAIR
References:
citation: Becker H, Marcucci G, Maharry K, Radmacher MD, Mrozek K, Margeson D, Whitman SP, Paschka P, Holland KB, Schwind S, Wu YZ, Powell BL, Carter TH, Kolitz JE, Wetzler M, Carroll AJ, Baer MR, Moore JO, Caligiuri MA, Larson RA, Bloomfield CD. Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood. 2010 Aug 5;116(5):788-92. doi: 10.1182/blood-2010-01-262543. Epub 2010 May 4.
citation: Fobare S, Kohlschmidt J, Ozer HG, Mrozek K, Nicolet D, Mims AS, Garzon R, Blachly JS, Orwick S, Carroll AJ, Stone RM, Wang ES, Kolitz JE, Powell BL, Oakes CC, Eisfeld AK, Hertlein E, Byrd JC. Molecular, clinical, and prognostic implications of PTPN11 mutations in acute myeloid leukemia. Blood Adv. 2022 Mar 8;6(5):1371-1380. doi: 10.1182/bloodadvances.2021006242.
citation: Mims AS, Kohlschmidt J, Borate U, Blachly JS, Orwick S, Eisfeld AK, Papaioannou D, Nicolet D, Mromicronzek K, Stein E, Bhatnagar B, Stone RM, Kolitz JE, Wang ES, Powell BL, Burd A, Levine RL, Druker BJ, Bloomfield CD, Byrd JC. A precision medicine classification for treatment of acute myeloid leukemia in older patients. J Hematol Oncol. 2021 Jun 23;14(1):96. doi: 10.1186/s13045-021-01110-5.
citation: Walker CJ, Kohlschmidt J, Eisfeld AK, Mrozek K, Liyanarachchi S, Song C, Nicolet D, Blachly JS, Bill M, Papaioannou D, Oakes CC, Giacopelli B, Genutis LK, Maharry SE, Orwick S, Archer KJ, Powell BL, Kolitz JE, Uy GL, Wang ES, Carroll AJ, Stone RM, Byrd JC, de la Chapelle A, Bloomfield CD. Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia. Clin Cancer Res. 2019 Nov 1;25(21):6524-6531. doi: 10.1158/1078-0432.CCR-19-0725. Epub 2019 Aug 2.