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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Chronic Myeloid Leukemia

Intervention / Treatment
-----------------
* Other: Discontinuation of therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Discontinuation<br>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<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free survival | 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 | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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