HDAC Inhibitor Valproic Acid as an Effective Therapy for Chronic Lymphocytic Leukemia

• Status: Terminated
• Trial end date: 2011-07-01
• Target enrollment: 0
• Participant gender: All

Summary

OBJECTIVES

To investigate:

• the mechanism of Valproic Acid (VPA)-induced apoptosis in B-CLL

• the ability of VPA in combination with standard chemotherapy or new antitumor agents to induce a synergistic antitumor effect in chronic lymphocytic leukemia (CLL) cells

• the clinical efficacy of VPA in previously treated CLL patients.

This will be an example of a translational research study where the results of our laboratory studies will be applied to a clinical trial in the CLL clinic at CancerCare Manitoba.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CancerCare Manitoba
• Collaborator: The Leukemia and Lymphoma Society
• Treatments: Fludarabine; Fludarabine phosphate; Histone Deacetylase Inhibitors; Valproic Acid

Criteria

Inclusion Criteria:

• Active CLL (as defined by the National Cancer Institute Working Group)

• Patients must have received at least one prior therapy for CLL and have been treated with a nucleoside analogue.

• Recruitment will be limited to those with an ECOG performance status of 2 or less.

Exclusion Criteria:

• Patients who are pregnant or breastfeeding

• Patients with a history of autoimmune cytopenias

• Patients with platelets < 50 x 109/L or an absolute neutrophil count < 1.5X109/L

• Patients with hepatic disease or an AST/ALT 6x above the upper limit of normal

• Patients with a calculated creatinine clearance < 30 ml/min using the Cockroft and Gault formula

• Patients with a history of pancreatitis

• Patients who are receiving drugs that affect VPA protein binding or metabolism

• Patients with active infection, HIV or active viral hepatitis

• Patients with active secondary malignancy or who have central nervous system involvement with CLL

• Patients diagnosed with more an aggressive lymphoproliferative disorder such as Richter's transformation