Dasatinib and Cyclosporine in Patients With Chronic Myelogenous Leukemia (CML)

Inclusion Criteria:

Patients must have a diagnosis of

- de novo chronic phase Ph+ CML, and not have received therapy with a tyrosine kinase
inhibitor (TKI) for more than 2 weeks prior to enrollment.

- OR chronic phase Ph+ CML refractory to or with intolerance of treatment with imatinib
or nilotinib therapy. Patients being treated with dasatinib who have refractory
disease may be considered for inclusion, at the discretion of the PIs, if other
therapeutic options are not deemed likely to be efficacious (e.g. previous
intolerance or refractoriness to nilotinib). Evaluation for and consideration of
hematopoietic stem cell transplantation as appropriate to the patient's condition by
the patient's primary treating hematologist/oncologist should occur prior to
enrollment in this trial.

- OR chronic phase Ph+ CML, without complete molecular remission after 3 months of
treatment with imatinib, nilotinib or dasatinib.

- OR accelerated phase Ph+ CML, for which allogeneic hematopoietic stem cell
transplantation is being planned, and for which no cytotoxic chemotherapy is planned
prior to conditioning, and can be reasonably expected to participate for a minimum of
one month prior to transplantation.

- OR accelerated phase Ph+ CML, for which allogeneic hematopoietic stem cell
transplantation is not a therapeutic option (due to age or lack of acceptable donor,
for example), and can be reasonably expected to participate for a minimum of one
month.

Prior Therapy

- Patients must have discontinued imatinib, nilotinib or dasatinib at least 7 days
prior to starting study therapy; this washout period may be omitted at the discretion
of the PIs, if it is determined that the washout may adversely affect patient care.

- Patients must discontinue hydroxyurea or interferon at least 7 days prior to starting
study therapy.

Age >18 years.

Life expectancy of greater than 1 month.

ECOG performance status ≤2 (Karnofsky >60%).

Patients must have normal organ and marrow function as defined below:

- leukocytes >3,000/mcL

- absolute neutrophil count >1,000/mcL

- absolute CD4+ count > 350/mcL

- platelets >100,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

- creatinine within normal institutional limits OR

- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal

The effects of dasatinib on the developing human fetus are unknown. For this reason and
because PTK inhibitors are known to be teratogenic, women of childbearing potential must
have a negative pregnancy test within 7 days of study entry. Women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry and for the duration of study
participation and for a minimum of 30 days following discontinuation of study therapy.
Should a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately.
Lactating women must agree not to nurse a child while on this trial or within 30 days of
discontinuation of study therapy.

Ability to understand and the willingness to sign a written informed consent document.