Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome
Intervention: Nilotinib+mVPD
Intervention description: 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-)
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
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
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
Maintenance
◦Nilotinib 400mg bid/d (during 2 years, for patients without alloHCT)
Consider alloHCT
Intervention MeSH terms: Cytarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 91.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia

Summary:

      RATIONALE: Nilotinib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth
      of cancer cells, either by killing the cells or by stopping them from dividing. Giving
      nilotinib together with combination chemotherapy may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving nilotinib together with combination
      chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.
    

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