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

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.