| Eligibility |
Inclusion Criteria:
1. Patients with non-blast phase CML by standard definition. This should be confirmed by
presence of the Philadelphia chromosome or variants of the (9;22) translocation by
cytogenetics, FISH or with a positive RT-PCR for BCR-ABL. Repeat marrow not required
for enrollment although documentation of current chronic phase disease is required.
Chronic Phase CML is defined as follows:
1. <15% blasts in peripheral blood and marrow
2. <30% blasts plus promyelocytes in peripheral blood and marrow
3. <20% basophils in peripheral blood
4. >100 x 109/L platelets
5. No evidence of extramedullary leukemic involvement with the exception of
hepatosplenomegaly.
Accelerated Phase CML is defined as follows:
1. <30% blasts in blood, marrow or both
2. No evidence of extramedullary leukemic involvement with the exception of
hepatosplenomegaly.
2. > 18 years of age and able to provide informed consent
3. Patients must have been on TKI therapy for CML for at least 1 year prior to enrollment
at minimum goal doses.
Imatinib 300mg PO daily Dasatinib 70mg PO daily Nilotinib 200mg PO BID Bosutinib 300mg
PO daily Ponatinib 30mg PO daily Lower than goal doses are allowed IF documented by
the treating physician that the goal dose was not tolerable due to toxicity.
4. Patient must have been on their most recent TKI consistently for at least 6 months
prior to enrollment on study
5. Must be expected to remain on current TKI for at least 6 months following last
infusion, unless there is progression of disease.
6. Detectable BCR-ABL transcripts measured by RT-PCR at a CLIA-approved laboratory and
reported on the IS with a value of >0.01% within 28 days prior to study enrollment.
The chosen RT-PCR test must be sensitive enough to detect a 4.5 log reduction in
BCR/ABL transcripts measured in peripheral blood.
7. Performance status must be ECOG PS 0, 1, or 2.
8. Woman of childbearing potential and is willing to use 2 highly effective methods of
contraception while receiving study treatment and for an additional 3 months after the
last dose of protocol-specified therapy. Male who has a female partner of childbearing
potential, and is willing to use 2 highly effective forms of contraception for at
least an additional 3 months after the last dose of protocol-specified therapy.
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from the study:
1. Current blast crisis phase disease by standard definition from the NCCN
2. Pregnant or lactating females
3. On other investigational agents for CML within 4 weeks of study enrollment
4. Platelets of <50,000/mm3, ANC <500/mm3 or hemoglobin < 7.5 g.dL
5. Abnormal screening laboratory values as defined below:
1. AST (SGOT) and/or ALT (SGPT) and/or alkaline phosphatase = 5 x upper limit of
normal (ULN)
2. Total bilirubin >1.5 x ULN (unless related to Gilbert´s or Meulengracht disease
or leukemic infiltration)
3. Creatinine = 3 ULN or creatinine clearance < 50 mL/min (calculated)
4. Those with residual toxicity of >grade 1 from prior therapy in areas that may be
expected to worsen over time; those with residual toxicities of grade 2 which are
stable prior to enrollment and the natural history of which would be expected to
be 'no change' over time are allowed; those with grade 3 or 4 residual toxicities
are not.
6. Positive test for human immunodeficiency virus (HIV) infection or known acquired
immunodeficiency syndrome (AIDS)
7. Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or
chronic infection (those with prior infection that is now post treatment and PCR
negative are allowed)
8. Current use of immunosuppressive medications at the time of study enrollment and
within 2 weeks of any study treatments, except:
1. Intranasal, inhaled, topical steroids, or local steroid injection
2. Systemic corticosteroids at physiologic doses =10 mg/day of prednisone or
equivalent
3. Steroids as premedication for hypersensitivity reactions at physiologic doses =10
mg/day of prednisone or equivalent
9. Patients with other major medical or psychiatric illnesses, which the treating
physician feels, could seriously compromise tolerance or compliance to this protocol.
10. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive
therapy
11. Any of the following in the previous 6 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or
symptomatic pulmonary embolism
12. Known prior or suspected hypersensitivity to study drugs or any component in their
formulations
13. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
disease not requiring immunosuppressive treatment are eligible
14. Diagnosis of any other malignancy within 3 years, except for adequately treated basal
cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix,
low grade prostate cancer on surveillance without any plans for treatment
intervention, or prostate cancer that has been adequately treated with prostatectomy
or radiotherapy and currently with no evidence of disease or symptoms
15. Active infection requiring systemic therapy
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