Discontinuation of Imatinib Mesylate in Patients With Chronic-Phase Chronic Myeloid Leukemia Previously Treated With Interferon-Alpha

November 11, 2016 updated by: University of Michigan Rogel Cancer Center

Discontinuation of Tyrosine Kinase Inhibitor Therapy in Patients With Chronic-Phase Chronic Myeloid Leukemia, Previously Treated With Interferon-Alpha

To investigate whether patients with chronic-phase chronic myeloid leukemia (CP-CML) previously treated with interferon-alpha (IFN) and presently on a tyrosine kinase inhibitor (TKI) (imatinib mesylate, dasatinib, or nilotinib) with achievement of a complete cytogenetic and at least a major molecular remission, are able to discontinue therapy and maintain a durable remission. Relapse-free survival (RFS) rate at 1 year after discontinuation of TKI will be the measurement of this objective.

Study Overview

Status

Status

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

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.

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.
Observational

Enrollment (Actual)

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.
7

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
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Cancer Center

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

Sampling Method

Non-Probability Sample

Study Population

Diagnosed with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase.

Description

Inclusion Criteria:

  1. Patients must have a diagnosis of Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase.
  2. Patients must have received prior therapy with interferon-alpha for their CML, for a period of at least 2 years, and achieved at least a partial cytogenetic response on this therapy, defined as 1% - 34% Ph+ cells in metaphase, present in the bone marrow.
  3. Patients must be actively receiving treatment for their CML with a TKI (imatinib mesylate, dasatinib, nilotinib). If patients are receiving dasatinib or nilotinib, this can only be for reasons other than imatinib-resistant CML.

  4. Patients must have an ongoing complete hematologic response (CHR) on a TKI, defined as follows:

    • WBC ≤ 10 x 109/L.
    • Platelet count < 450,000 x 109/L.
    • No blasts or promyelocytes in peripheral blood.
    • No evidence of disease-related symptoms and extramedullary disease, including the liver and spleen.
  5. Patients must have a complete cytogenetic response (CCyR) on a TKI for a minimum of one year leading up to enrollment. Complete cytogenetic response is defined as 0% Ph+ cells in metaphase, in the bone marrow and/or a negative peripheral blood FISH analysis for the BCR/ABL gene fusion, and an ongoing CCyR must be confirmed by bone marrow aspirate cytogenetics and/or peripheral blood FISH for BCR/ABL within 4 weeks of discontinuing therapy.
  6. Patients must have at least a major molecular remission on a TKI for a minimum of 1 year, present on 2 consecutive analyses, performed at least 3 months apart, in the 6 to 12 months leading up to enrollment. Major molecular remission is defined as ≥ 3 log reduction from a standard baseline value (equivalent to a BCR-ABL/ABL of ≤ 0.1%) in BCR/ABL transcript by quantitative RT-PCR performed on peripheral blood or bone marrow aspirate. Complete molecular remission is defined as a negative quantitative RT-PCR (QPCR) analysis for BCR/ABL, present on 2 consecutive analyses, performed at least 3 months apart, in the 6 to 12 months leading up to enrollment.
  7. Patients must be eighteen years of age or older
  8. Patients must have an ECOG performance status of 0-2 (Appendix 13.1)
  9. All patients must be informed of the investigational nature of this study and standard alternative therapy. All patients must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

  1. Patients who have had prior progression of their CML to accelerated phase or blast crisis.
  2. Patients who have previously undergone hematopoietic stem cell transplantation.
  3. Patients receiving dasatinib or nilotinib due to a prior history of imatinib-resistant CML.
  4. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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.
Discontinuation
Subjects who agree to discontinue their tyrosine kinase inhibitor(TKI)therapy, namely,imatinib mesylate, dasatinib, or nilotinib,and then followed to see if they can maintain a durable remission.
Other: Discontinuation of therapy
Patients with chronic-phase chronic myeloid leukemia (CP-CML) previously treated with interferon-alpha (IFN) and presently on a tyrosine kinase inhibitor (TKI) (imatinib mesylate, dasatinib, or nilotinib) with achievement of a complete cytogenetic and at least a major molecular remission.

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
Measure Description
Time Frame
Relapse-free survival
Time Frame: 1 year
Relapse-free survival (RFS) rate at 1 year after discontinuation of TKI will be the measurement of this objective.
1 year

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
Measure Description
Time Frame
Reduction of the malignant stem cell population
Time Frame: 1 Year
To determine whether prior treatment with interferon-alpha followed by TKI therapy effectively depletes/reduces the malignant stem cell population in CP-CML.
1 Year

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 Michigan Rogel Cancer Center

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: Dale Bixby, M.D./PhD, University of Michigan Rogel Cancer Center

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.
May 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2011

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).
February 19, 2010

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.
February 22, 2010

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.
February 23, 2010

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.
November 15, 2016

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.
November 11, 2016

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.
November 1, 2016

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.
  • UMCC 2008.083
  • HUM00021950 (Other Identifier: University of Michigan Medical IRB)

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings