Dipeptidylpeptidase IV (CD26) on Philadelphia-positive leukemic stem cells (LSC) as marker and novel therapeutic target in chronic myeloid leukemia (CML).

1. Patients >=18 years of age.
2. At diagnosis chronic myeloid leukemia in chronic phase.
3. Previous relapse during attempt at TFR (Treatment Free Remission)
4. Documented regain of deep molecular remission at the level of at least
MR4.0, defined as a measurable BCR-ABL level <=0.01% IS or an undetectable
BCR-ABL with a minimal total control gene copy number of ABL1 *10*000 or GUSB
*24*000 in two replicates. A sample showing MR4.0 or better needs to have been
taken within 31 days of study inclusion.
5. Continuous treatment with any TKI for a minimum of 12 months prior to
entering the study
6. No other current or planned anti-leukemia therapy.
7. ECOG Performance status 0,1, or 2.
8. Adequate organ function as defined by:
a) Total bilirubin <1.5 x ULN (ULN = local lab upper limit of normal). Does not
apply to patients with isolated hyperbilirubinemia (e.g. Gilbert*s disease)
grade <3.
b) ASAT and ALAT <2.5 x ULN.
c) Serum amylase and lipase <=1.5 x ULN.
d) Alkaline phosphatase <=2.5 x ULN.
e) Creatinine clearance >30 ml/min.
f) Mg++, K+ >=LLN.
9. Life expectancy of more than 12 months in the absence of any intervention
10. Written informed consent to participate in the study

1. Prior accelerated phase or blast crisis.
2. Patient has received another investigational agent within last 6 months.
3. Prior stem cell transplantation.
4. History of occlusive cardiovascular disease, including peripheral occlusive
arterial disease, cerebrovascular disease and coronary artery disease.
5. Other clinically significant uncontrolled heart disease (e.g. unstable
angina, congestive heart failure or uncontrolled hypertension)
6. Increased risk of cardiac arrhythmia, defined as:
a) Inability to monitor the QT/QTc interval on ECG.
b) Long QT syndrome or a known family history of long QT syndrome.
c) Clinically significant resting brachycardia (<50 beats per minute).
d) QTc >450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec
and electrolytes are not within normal ranges, electrolytes should be corrected
and then the patient re-screened for QTc.
e) History of or presence of clinically significant ventricular or atrial
tachyarrhythmias
6. Known atypical BCR-ABL transcript not quantifiable by standard RQ-PCR
7. History of active malignancy during the past 2 years with the exception of
basal carcinoma of the skin or carcinoma in situ of cervix uteri or breast.
8. Acute liver disease or cirrhosis.
9. Previous or active acute or chronic pancreatic disease.
10. Another severe and/or life-threatening medical disease.
11. History of significant congenital or acquired bleeding disorder unrelated
to cancer.
12. Impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of study drug.
13. Patients actively receiving therapy with strong CYP3A4 inhibitors where the
treatment cannot be either discontinued or switched to a different medication
prior to starting study drug.
14. Patients who are currently receiving treatment with any medication that has
the potential to prolong the QT interval and the treatment cannot be either
discontinued or switched to a different medication prior to starting study drug.
15. Patients who are:
a) pregnant.
b) breast feeding.
c) of childbearing potential without a negative pregnancy test prior to
baseline.
d) male or female of childbearing potential unwilling to use contraceptive
precautions throughout the trial (post-menopausal women must be amenorrheic for
at least 12 months to be considered of non-childbearing potential).
16. Interruption of TKI therapy for a cumulative period in excess of 21 days in
the preceding 3 months.
17. Known intolerance to nilotinib
18. Known intolerance to vildagliptin
19. History of non-compliance, or other inability to grant informed consent.
20. Past or present history of alcohol abuse, use of illicit drugs, or severe
psychiatric disorders, including depression.
21. Autoimmune hepatitis or a history of autoimmune disease.
22. Pre-existing thyroid disease unless it can be controlled with conventional
treatment.
23. Epilepsy and/or compromised central nervous system (CNS) function.
24. HCV/HIV patients.
25. Poorly controlled diabetes mellitus(i.e. HbA1c >9.0) or
clinically relevant diabetic complications such as neuropathy, retinopathy,
nephropathy, coronary or peripheral vascular disease.