A Phase II Study of Gleevec and Arsenic Trioxide in Patients With CML Who Fail Gleevec

September 18, 2011 updated by: New Mexico Cancer Care Alliance

A Phase II Study of Gleevec and Arsenic Trioxide in Patients With CML Who Fail to Achieve a Complete Response to Initial Gleevec Treatment

1.0 OBJECTIVES 1.1 To test the activity of arsenic trioxide in combination with imatinib in patients with CML with cytogenetic evidence of residual disease.

1.2 To determine the toxicity associated with this therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Drug: Gleevec and Arsenic Trioxide

Detailed Description

Chronic myelogenous leukemia (CML) results from the clonal expansion of immature myeloid cells with the t (9,22) (Ph) translocation, that encodes the constitutively active tyrosine kinase oncogene, bcr/abl. Patients with chronic phase CML are currently being treated with either hemopoetic stem cell transplantation (HSCT), or with the recently approved tyrosine kinase inhibitor, imatinib. Previous data, using interferon in patients with CML, has shown that patients who do not achieve a major cytogenetic response (defined as >35% Ph+) have a shortened survival. These patients are often considered for HSCT. However, due to constraints of age, suitable donor, and patient choice, only a minority of patients will undergo this potentially curative procedure.
The aim of this study is to create a uniform approach to the treatment of CML in New Mexico, with an aim of achieving complete cytogenetic response as the primary goal. A graded approach will be taken, starting out with the standard treatment (imatinib 400 mg per day), and then in patients identified as poor responders an imatinib, and arsenic combination will be offered to patients. It is hoped to find a complete cytogenetic response that exceeds the ~20% response with gleevec 800mg per day.

Study Type

Interventional

Enrollment (Actual)

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 Mexico
  - Albuquerque, New Mexico, United States, 87131
    - University of New Mexico
  - Santa Fe, New Mexico, United States, 87505
    - New Mexico Cancer Care Associates

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

Genders Eligible for Study

All

Description

Inclusion criteria:

All patients, 18 years of age or older, with a diagnosis of CML.
Patients must have a life expectancy of at least 12 weeks.
Patients must have an ECOG performance status of 0-2.
Patients must sign an informed consent.
Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and SGOT or SGPT < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine < 1.5 x upper limit of normal.
Patients with CML in chronic phase on gleevec as first line therapy who fulfill the following criteria:
Failure to achieve a complete hematologic response (CHR) after 3 months of therapy (hematologic resistance)
Failure to achieve a complete cytogenetic response (CGCR) after > 9 months of therapy.
Cytogenetic relapse, defined as an increase in the Ph+ cells by at least 30%.
Hematologic relapse defined as the appearance of any of the following, confirmed by a second determination > 1 month later:
- WBC count >20, 000,
- Platelet count >600,000,
- Progressive splenomegaly > 5 cm below the left intercostals margin,
- >5% myelocytes and/or metamyelocytes in the peripheral blood,
- Blasts or promyelocytes in the peripheral blood

Exclusion Criteria:

Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception.
Patients may receive no other concurrent chemotherapy or radiation therapy during this trial.
Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To test the activity of arsenic trioxide in combination with imatinib in patients with CML with cytogenetic evidence of residual disease Time Frame: 2 years	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the toxicity associated with this therapy Time Frame: 2 years	2 years

Collaborators and Investigators

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

Sponsor

New Mexico Cancer Care Alliance

Investigators

Principal Investigator: Ian Rabinowitz, MD, University of New Mexico

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

April 1, 2004

Primary Completion (Actual)

April 1, 2005

Study Completion (Actual)

March 1, 2006

Study Registration Dates

First Submitted

November 3, 2005

First Submitted That Met QC Criteria