- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01073436
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
Conditions
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
-
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Michigan
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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:
- Patients must have a diagnosis of Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase.
- 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.
- 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.
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.
- 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.
- 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.
- Patients must be eighteen years of age or older
- Patients must have an ECOG performance status of 0-2 (Appendix 13.1)
- 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:
- Patients who have had prior progression of their CML to accelerated phase or blast crisis.
- Patients who have previously undergone hematopoietic stem cell transplantation.
- Patients receiving dasatinib or nilotinib due to a prior history of imatinib-resistant CML.
- 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
Terms related to this study
Keywords
- Informed Consent
- diagnosis of Ph+) CML in chronic phase.
- prior therapy with interferon-alpha for at least 2 years, and achieved at least a partial cytogenetic response
- receiving a TKI (imatinib mesylate, dasatinib, nilotinib)
- 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
- complete cytogenetic response (CCyR) on a TKI for a minimum of 1 yr
- major molecular remission on a TKI for a minimum of 1 yr
- 18 years of age or older
- ECOG performance status of 0-2 (Appendix 13.1)
Additional Relevant MeSH Terms
Other Study ID 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.
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