Intervention: Cytidine
Trial phase: Phase 2
ATC code: L01BC01 | L01XY01
SMILES: Nc1ccn(C2OC(CO)C(O)C2O)c(=O)n1
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 91
Group description: Patients who were Philadelphia-positive, newly-diagnosed adult ALL and treated with nilotinib + mVPD treatment plan

Nilotinib+mVPD: 1.Induction:

Daunorubicin 90 mg/m2/day by continuous iv infusion (d1-3)
Vincristine 2 mg iv push (d1, 8, 15, 22)
Prednisolone 60 mg/m2/day po (d1-28)
Nilotinib 400mg bid/d (d8-) 2.Consolidation A (cycle1)
Daunorubicin 45 mg/m2/day by continuous iv (d1, 2)
Vincristine 2 mg iv (d1, 8)
Prednisolone 60 mg/m2/day po (d1-14)

Nilotinib 400mg bid/d

3. Consolidation B (cycles 2&4)

Cytarabine 2,000 mg/m2/day iv over 2 hours (d1-4)
Etoposide 150 mg/m2/day iv over 3 hours (d1-4)

Nilotinib 400mg bid/d

4.Consolidation C (cycles 3&5)

Methotrexate 220 mg/m2 iv bolus, then 60mg/m2/h for 36 hours (d1-2, 15-16)
Leucovorin followed immediately by 50 mg/m2 iv every 6hrs for three doses,

Nilotinib 400mg bid/d

5.Maintenance

Nilotinib 400mg bid/d (during 2 years, for patients without alloHCT)

6.Consider alloHCT
Eligibility criteria:
DISEASE CHARACTERISTICS:

Newly diagnosed acute lymphoblastic leukemia or acute mixed lineage leukemia

Positive for Bcr-Abl fusion transcript (Philadelphia chromosome-positive disease) by RT-PCR

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Total bilirubin < 2 mg/dL
SGOT < 3 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN (unless considered tumor-related)
Creatinine < 2.0 mg/dL ULN
Serum amylase and lipase ≤ 1.5 times ULN
Potassium, magnesium, and phosphorus normal (supplementation allowed)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No rare hereditary problems with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption
No known sensitivity to any of the study drugs
No severe medical condition that, in the opinion of the investigator, would preclude study participation

No impaired cardiac function, including any of the following:

LVEF < 45% or below the lower limit of normal by ECHO
Long QT syndrome or known family history of long QT syndrome
Clinically significant resting bradycardia (< 50 beats per minute)
QTc > 450 msec on baseline ECG (using the QTcF formula)
Myocardial infarction within the past 12 months

Other clinically significant heart disease, including any of the following:

Unstable angina
Congestive heart failure
Uncontrolled hypertension
Uncontrolled arrhythmias
No other primary malignant disease requiring systemic treatment
No acute or chronic liver, pancreatic, or severe renal disease
No other severe and/or life-threatening medical disease
No history of significant congenital or acquired bleeding disorder unrelated to cancer
No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
No history of non-compliance

PRIOR CONCURRENT THERAPY:

More than 30 days since prior investigational agents
No concurrent medications that have the potential to prolong the QTc interval
No concurrent strong CYP3A4 inhibitors
No concurrent therapeutic coumarin derivatives