Trial Information

Molecular Markers Of Chronic Lymphocytic Leukemia

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.