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

Terminated

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

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

    • 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

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
Intervention / Treatment
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.
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

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

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.

Investigators

  • 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

May 1, 2009

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

February 19, 2010

First Submitted That Met QC Criteria

February 22, 2010

First Posted (Estimate)

February 23, 2010

Study Record Updates

Last Update Posted (Estimate)

November 15, 2016

Last Update Submitted That Met QC Criteria

November 11, 2016

Last Verified

November 1, 2016

More Information

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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