Clinical trial NCT01005368: Study of Biomarkers in Blood and Bone Marrow Samples From Patients With Previously Untreated Chronic Lymphocytic Leukemia
Official title: Molecular Markers Of Chronic Lymphocytic Leukemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Leukemia
Keywords: chronic lymphocytic leukemia
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-10-30
Enrollment: 600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with chronic lymphocytic leukemia and were previously untreated. The patients must have also previously enrolled on a Cancer and Leukemia Group B protocol.

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of chronic lymphocytic leukemia

  * Previously untreated disease
* Registered to receive treatment on a Cancer and Leukemia Group B protocol

PATIENT CHARACTERISTICS:

* Not specified

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: complete response
timeFrame: Up to 10 years
measure: prolonged progression-free survival
timeFrame: Up to 10 years
measure: overall survival
timeFrame: Up to 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Kaiser Permanente Medical Office -Vandever Medical Office
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: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
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: Bethesda
country: United States
facility: National Naval Medical Center
state: Maryland
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Cape Girardeau
country: United States
facility: Southeast Cancer Center
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Jefferson City
country: United States
facility: Goldschmidt Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Grand Island
country: United States
facility: Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center
state: Nebraska
city: North Platte
country: United States
facility: Callahan Cancer Center at Great Plains Regional Medical Center
state: Nebraska
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
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: 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: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
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
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: John C. Byrd, MD
role: STUDY_CHAIR
References: