A Study of Enzastaurin in Patients With Leukemia

Study Overview
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Brief Summary
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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.

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

Conditions
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Leukemia, Lymphocytic

Intervention / Treatment
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* Drug: enzastaurin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are eligible to be included in the study only if they meet all of the following criteria: Patients with B-cell CLL as diagnosed by expression of CD19, CD5, and CD23 by flow cytometry. Rai Stage III or IV disease or earlier stage disease with indications for therapy per NCI Working Group criteria (Cheson et al. 1996) Absolute lymphocyte count > or = to 5,000/microliter, with a lymphocyte WBC differential of > or = to 70%. Platelet count >20,000/microliter. 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: Are unable to swallow tablets. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin. Are pregnant or breastfeeding. 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). 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: enzastaurin<br>* 1125 mg loading dose then 500 mg, oral, daily, up to 3 years or until progressive disease<br>* Other names: LY317615;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the inhibitory effects of enzastaurin on the pGSK3 beta level in B-CLL cells. |  | baseline, cycle 1, end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of activity of PKC beta in B-CLL cells |  | baseline, end of study | 
| Response rate |  | baseline to measured progressive disease | 
| Duration of response |  | time of response to progressive disease | 
| Time to progressive disease |  | baseline to measured progressive disease | 
| Safety |  | every cycle |