Study of Biomarkers in Blood and Bone Marrow Samples From Patients With Previously Untreated Chronic Lymphocytic Leukemia
- Conditions
- Leukemia
- Interventions
- Genetic: fluorescence in situ hybridizationGenetic: mutation analysisGenetic: nucleic acid sequencingGenetic: polymerase chain reactionGenetic: western blottingOther: flow cytometryOther: laboratory biomarker analysis
- Registration Number
- NCT01005368
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.
PURPOSE: This research study is looking at biomarkers in blood and bone marrow samples from patients with previously untreated chronic lymphocytic leukemia.
- Detailed Description
OBJECTIVES:
* Determine the relevance of common and uncommon interphase cytogenetic abnormalities related to baseline clinical features, complete response (CR), prolonged progression-free survival (PFS), and overall survival (OS) in patients with previously untreated chronic lymphocytic leukemia.
* Determine the significance of the absence of IgV_H gene mutational status as related to the ability to predict CR, PFS, and OS in these patients.
* Correlate IgV_H gene mutational status with CD38 expression, ZAP-70 expression, over-expression of Mcl-1, BAK-1, high Mcl-1:Bax ratio, p53 mutations or dysfunction, high-risk karyotype abnormalities, and other molecular features associated with poor outcome in these patients.
* Determine the prognostic significance of over-expression of Mcl-1, BAK-1, high Mcl-1:Bax ratio, p53 mutations or dysfunction, ATM mutation, ATM expression, and other factors that disrupt apoptosis with respect to CR, prolonged PFS, and OS.
* Determine if clonal evolution occurs in these biological markers at partial response or disease relapse.
OUTLINE: This is a multicenter study.
Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 600
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group 1 flow cytometry Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function. Group 1 fluorescence in situ hybridization Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function. Group 1 mutation analysis Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function. Group 1 nucleic acid sequencing Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function. Group 1 polymerase chain reaction Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function. Group 1 laboratory biomarker analysis Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function. Group 1 western blotting Blood and bone marrow is collected at baseline, 3 months after completion of induction therapy, 2 months after completion of consolidation therapy, 1 year after completion of study treatment, and at disease relapse. Samples are analyzed by FISH for interphase cytogenetics, PCR for IgV_H mutational status, flow cytometry for surface expression of CD38 cells, western blot to assess Mcl-1, Bcl-2, BAK-1, ATM, ZAP-70, and Bar expression, and sequencing for p53 and ATM function.
- Primary Outcome Measures
Name Time Method complete response Up to 10 years prolonged progression-free survival Up to 10 years overall survival Up to 10 years
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (35)
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸Columbia, Missouri, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Kinston Medical Specialists
🇺🇸Kinston, North Carolina, United States
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
CancerCare of Maine at Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Harold Alfond Center for Cancer Care
🇺🇸Augusta, Maine, United States
Goldschmidt Cancer Center
🇺🇸Jefferson City, Missouri, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Mountainview Medical
🇺🇸Berlin, Vermont, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Louis A. Weiss Memorial Hospital
🇺🇸Chicago, Illinois, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Callahan Cancer Center at Great Plains Regional Medical Center
🇺🇸North Platte, Nebraska, United States
McLeod Regional Medical Center
🇺🇸Florence, South Carolina, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
CCOP - Hematology-Oncology Associates of Central New York
🇺🇸East Syracuse, New York, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Wayne Memorial Hospital, Incorporated
🇺🇸Goldsboro, North Carolina, United States
New York Weill Cornell Cancer Center at Cornell University
🇺🇸New York, New York, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Cancer Center
🇺🇸Saint Louis, Missouri, United States
Fletcher Allen Health Care - University Health Center Campus
🇺🇸Burlington, Vermont, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center
🇺🇸Grand Island, Nebraska, United States
Pardee Memorial Hospital
🇺🇸Hendersonville, North Carolina, United States
Kaiser Permanente Medical Office -Vandever Medical Office
🇺🇸San Diego, California, United States
National Naval Medical Center
🇺🇸Bethesda, Maryland, United States
Veterans Affairs Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States