Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia

August 2, 2007 updated by: University of Bologna

Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia Who Are Resistant to or Intolerant of *-Interferon. A Phase II Study

This is a Phase II, open-label, multi-center trial designed primarily to evaluate the rate of complete or major cytogenetic response of STI571 as demonstrated by a decrease in the percentage of Ph chromosome positive cells in the bone marrow, in patients with CML who are refractory to or intolerant of interferon-alpha.

During the core phase of the study, patients will receive once daily oral administration of STI571 at a dose of 400 mg, for up to 12 months. After completing 12 months of therapy patients may be eligible to receive additional therapy provided that, in the opinion of the investigator, the patient has benefited from treatment with STI571 and in the absence of safety concerns. Patients will receive STI571 on an outpatient basis.

During the extended phase (which is of indefinite duration), patients may continue STI571 until either progression to accelerated phase, blast phase, death, the development of intolerable toxicity, or the investigator feels it is no longer in the patient's best interest to continue therapy, whichever comes first. The number of visits will be at a reduced frequency. Patients who discontinue study drug will be followed for survival for up to 5 years.

STI571 will be considered active if the interferon-refractory patient population satisfies the target of achieving a complete or major response at a rate of at least 30%, within the preset error limits. Cytogenetic responses will be evaluated every three months and categorized as either complete (0% Ph+ chromosome cells), or major (1 to 35% Ph+ chromosome cells) responses. STI571 will be discontinued for any patient whose disease progresses to either the accelerated phase or blast crisis.

A minimum of 100 patients who are interferon refractory will receive STI571 administered at a dose of 400 mg once a day. In addition, the protocol is also open for patients who are intolerant to interferon-alpha in order to get a preliminary evaluation of their response to STI571 therapy. Up to 100 intolerant patients will be enrolled. Enrollment of intolerant patients will cease at 100, or whenever the 100 refractory patients are accrued, whichever comes first.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This Phase II trial will evaluate at least 100 patients for the rate of complete or major cytogenetic response of STI571 as demonstrated by a decrease in the percentage of Ph chromosome positive cells in the bone marrow in patients with CML who are refractory to or intolerant of interferon-alpha. Statistical considerations are based on the refractory patient population only. Intolerant patients are included as long as recruitment of the refractory patients is ongoing, up to a maximum of 100 intolerant patients, whichever comes first.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients * 18 years of age.
  2. Patients with Ph chromosome positive CML in the chronic-phase of the disease.

  3. Patients must have documented resistance to an interferon-alpha containing therapy, defined as any of the following:

    1. Hematologic Resistance - Failure to achieve a complete hematologic response, lasting for at least 1 month despite of 6 or more months of an interferon-alpha containing regimen.
    2. Cytogenetic Resistance - Bone marrow cytogenetics showing *65% Ph chromosome positivity after at least one year of interferon-alpha based therapy
    3. Cytogenetic Refractoriness - An increase in the Ph+ chromosome bone marrow cells by at least 30 percentage points (eg., from 20% to 50%, or from 30% to 60%) confirmed by two samples at least 1 month apart, or an increase to * 65%
    4. Hematologic Refractoriness - A rising WBC count (*100% increase and to a level *20 x 109/L confirmed by two samples taken at least two weeks apart) while receiving an interferon-alpha containing regimen.
  4. Patients who have demonstrated intolerance to interferon-alpha therapy defined as: a documented * Grade 3 non-hematologic toxicity (grade 2 in case of neurologic or neuropsichiatric toxicity), persisting for more than 2 weeks, in a patient receiving an interferon-alpha containing regimen. Patients who are intolerant to interferon-alpha must be more than 3 months from time of diagnosis.
  5. Written voluntary informed consent.

Exclusion Criteria:

  1. Patients of childbearing potential without a negative pregnancy test prior to the initiation of study drug. Barrier contraceptive precautions are to be used throughout the trial in both sexes.
  2. Serum bilirubin and creatinine concentrations more than twice the upper limit of the normal range.
  3. SGOT and SGPT more than twice the upper limit of the normal range.
  4. Percentage of blasts, or basophils in the peripheral blood or bone marrow > 15%.
  5. Percentage of blasts plus promyelocytes in the peripheral blood or bone marrow ( 30%.
  6. Patients with a platelet count < 100 x 109/L
  7. Patients with an ECOG Performance Status Score * 3.
  8. Patients receiving busulfan within 6 weeks of Visit 1.
  9. Patients receiving treatment with interferon-alpha within 14 days of Visit 1.
  10. Patients receiving treatment with cytosine arabinoside within 14 days of Visit 1.
  11. Patients receiving treatment with hydroxyurea within 7 days of Visit 1.
  12. Patients who have received other investigational agents within 28 days of Visit 1.
  13. Patients with Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria.
  14. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.
  15. Patients who are likely to be submitted to any transplantation procedure during the study period (12 months)

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
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
To determine the rate of complete and major cytogenetic response of STI571 as demonstrated by a decrease in the percentage of Ph chromosome positive cells in the bone marrow, in patients with CML who are refractory to interferon-alpha.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
To quantify the molecular response of STI571 as demonstrated by a decrease of bcr/abl transcript in peripheral blood cells,
To determine the rate and duration of complete hematological response,
To evaluate the duration of complete and major cytogenetic responses,
To evaluate the safety profile and improvement of symptomatic parameters,
To evaluate the time to accelerated disease, or blast crisis,
To evaluate overall survival,
To evaluate the rate and the duration of hematologic and cytogenetic response in patients intolerant to interferon-alpha

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Bologna

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michele Baccarani, MD, Istituto di Ematologia "L e A Seragnoli"-Policlinico S.Orsola-Malpighi di Bologna

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2000

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 2, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2007

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 3, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2007

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 2, 2007

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CML 002

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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