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

NCT00524667 | Terminated Phase 2

• 1 other identifier: CCM-001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Active CLL

Outcome Measures

Primary Outcomes (1)

• Best clinical response as defined by NCIWG criteria for CLL

  6 months after commencing therapy

Secondary Outcomes (1)

• Effect of treatment on histone acetylation status; hematological toxicity (graded according to NCIWG criteria for CLL) and nonhematological toxicity (graded according to NCI common toxicity criteria)

  throughout therapy

Study Arms (1)

1

EXPERIMENTAL

Drug: Valproic acid & fludarabine

Interventions

Valproic acid & fludarabine DRUG

valproic acid (VPA) starting dose of 15 mg/day p.o. in divided doses, increased weekly by 5 mg/kg/day until \>1mM Fludarabine 40 mg/m2/day orally will be added after completing 28 days of VPA if participant has been identified as having stable or progressive disease.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• CancerCare Manitoba: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (1)

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Related Links

• Official CancerCare Manitoba Website

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Valproic Acid; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• David Szwajcer, MD

  CancerCare Manitoba / University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 3, 2007
• Study Start: January 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 20, 2011

Record last verified: 2011-07

Locations

CA (1)