A Pilot Study of Pivanex in Patients With Chronic Lymphocytic Leukemia

August 26, 2005 updated by: Titan Pharmaceuticals

A Pilot Study of Pivanex, a Histone Deacetylase Inhibitor, in Patients With Chronic Lymphocytic Leukemia

This pilot study will assess the safety and efficacy of Pivanex alone in patients with chronic lymphocytic leukemia (CLL) who have relapsed or refractory disease after previous chemotherapy treatment. Pivanex is an investigational agent.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Rationale: Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of mature lymphocytes. These CLL lymphocytes are blocked from undergoing terminal differentiation and apoptosis. Patients with CLL have limited options for therapy, especially after the failure of standard chemotherapy regimens. Histone deacetylase inhibitors (HDACs) comprise a new class of drugs being evaluated in the treatment of various malignancies. In vitro data suggest that HDAC inhibition leads to terminal B-cell differentiation and may therefore play a therapeutic role in the treatment of CLL. Pivanex (pivaloyloxymethyl butyrate) is an HDAC inhibitor that has been shown to induce apoptosis of CLL lymphocytes in vitro. In previous clinical trials, Pivanex has been well tolerated. The goal of this protocol is to determine the effects of Pivanex in patients with CLL.

Purpose: This open-label trial will determine the response rate of Pivanex in patients with CLL.

Objectives: (1) Determine the response rate of Pivanex in patients with relapsed CLL; (2) Determine time to disease progression in patients with relapsed CLL treated with Pivanex; and (3) Determine the safety profile of Pivanex in CLL.

Design: This is an open label, single arm, multiple dose, pilot study of patients with relapsed CLL. Patients will be treated with 2.5 g/m2 of Pivanex administered intravenously over 6 hours daily on Days 1 - 3. Treatment will be repeated every 21 days until disease progression or the patient is withdrawn from treatment for protocol-specified reasons.

Disease status will be assessed prior to every odd-numbered treatment cycle using response criteria based upon the Revised National Cancer Institute-sponsored Working Group Guidelines for CLL. Patients withdrawn due to disease progression will be followed for survival. Patients withdrawn from study for reasons other than disease progression will be followed for disease progression and survival.

Study Type

Interventional

Enrollment

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Center for Lymphoma and Myeloma; Weill Medical College of Cornell University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have a confirmed diagnosis of CLL or small lymphocytic lymphoma (SLL) based upon the Revised NCI-sponsored Working Group guidelines for CLL;
  • Relapsed or refractory disease after previous chemotherapy treatment;
  • Age > 18 years;
  • Adequate renal function with creatinine <= 1.5 mg/dL;
  • Adequate liver function with alkaline phosphatase <= 2.5 X upper limit of normal, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT) <= 2.5 X upper limit of normal; and total bilirubin <= 2.0 X upper limit of normal;
  • Adequate bone marrow function as determined by having platelets > 50,000/mm3 without transfusion in the preceding 2 weeks and an absolute neutrophil count (ANC) => 1,500 cells/mm3 without growth factor support; unless cytopenias due to marrow infiltration;
  • Able to give informed consent;
  • A minimum of 4 weeks must have elapsed from the completion of any previous treatment regimen, including radiation and biologic therapies (6 weeks if a prior nitrosourea or mitomycin C, 12 weeks if radioimmunotherapy) to treatment on Day 1 Cycle 1. Patients must have recovery from treatment-associated toxicity(ies);
  • A predicted life expectancy of at least 6 months; and
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Exclusion Criteria:

  • More than three systemic treatment regimens for CLL/SLL (excluding immunotherapies and biologic therapies);
  • Concurrent malignancy that the patient has not been free of for at least 5 years, excluding curatively treated carcinoma-in-situ or non-melanoma skin cancer;
  • Any pregnant or lactating females. Females of childbearing potential must have a negative pregnancy test and all male and female patients of reproductive potential must agree to use adequate birth control;
  • Known HIV-positive patients;
  • Any underlying medical conditions or circumstances that would contraindicate therapy with study treatment, affect compliance or impair evaluation of study endpoints;
  • Receiving investigational agents within 4 weeks of the study treatment; and
  • Known allergy to reagents in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Titan Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Study Completion

April 1, 2005

Study Registration Dates

First Submitted

May 24, 2004

First Submitted That Met QC Criteria

May 25, 2004

First Posted (Estimate)

May 26, 2004

Study Record Updates

Last Update Posted (Estimate)

August 30, 2005

Last Update Submitted That Met QC Criteria

August 26, 2005

Last Verified

August 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PIV-801

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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