A Study of Enzastaurin in Patients With Leukemia

A Phase 1b Pharmacokinetic-Pharmacodynamic-Pharmacogenomic Study of Enzastaurin in Patients With B-Cell Chronic Lymphocytic Leukemia (B-CLL)

The primary objective of this study is to see if enzastaurin affects the pGSK3 beta level in B-cell chronic lymphocytic leukemia (B-CLL) cells.

Inclusion Criteria:

Patients are eligible to be included in the study only if they meet all of the following criteria:

1. Patients with B-cell CLL as diagnosed by expression of CD19, CD5, and CD23 by flow cytometry.

2. Rai Stage III or IV disease or earlier stage disease with indications for therapy per NCI Working Group criteria (Cheson et al. 1996)

3. Absolute lymphocyte count > or = to 5,000/microliter, with a lymphocyte WBC differential of > or = to 70%.

4. Platelet count >20,000/microliter.

5. Adequate organ function, including the following:

   • Hepatic: bilirubin < or = to 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) < or = to 2.5 x ULN
   • Renal: serum creatinine < or = to 1.5 X ULN.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

1. Are unable to swallow tablets.
2. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin.
3. Are pregnant or breastfeeding.
4. Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off of corticosteroids for at least 4 weeks before starting study therapy).
5. Have a serious concomitant systemic disorder (including active bacterial, fungal, or viral infection) that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol.