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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01073436
First received: February 19, 2010
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Chronic Myeloid Leukemia
Other: Discontinuation of therapy

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Discontinuation of Tyrosine Kinase Inhibitor Therapy in Patients With Chronic-Phase Chronic Myeloid Leukemia, Previously Treated With Interferon-Alpha

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Relapse-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Relapse-free survival (RFS) rate at 1 year after discontinuation of TKI will be the measurement of this objective.


Secondary Outcome Measures:
  • Reduction of the malignant stem cell population [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    To determine whether prior treatment with interferon-alpha followed by TKI therapy effectively depletes/reduces the malignant stem cell population in CP-CML.


Estimated Enrollment: 15
Study Start Date: May 2009
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01073436

Locations
United States, Michigan
University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Dale Bixby, M.D./PhD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01073436     History of Changes
Other Study ID Numbers: UMCC 2008.083, HUM00021950
Study First Received: February 19, 2010
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:
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)
Informed Consent

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Interferons
Interferon-alpha
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014