Stem Cell Monitoring for CML Patients Undergoing Nilotinib Therapy
Condition: Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: Nilotinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The study is an open-label phase 2 clinical and translational trial designed to evaluate the
      effects of nilotinib on the leukemic stem cell population in subjects with newly diagnosed
      chronic phase chronic myeloid leukemia (Ph+ CML in CP). Nilotinib is FDA-approved to treat
      subjects with Ph+ CML in CP. Subjects on study will be monitored according to accepted
      National Cancer Comprehensive Network [NCCN] clinical guidelines for 24 months. After 24
      months, if continued therapy is needed subjects will be transitioned to commercial supply of
      study drug.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients 18 years or older

          2. Eastern Cooperative Oncology Group (ECOG) Performance status 0,1, or 2

          3. Documented diagnosis of Ph+ Chronic phase CML:

               -  Chronic phase: None of the criteria for accelerated or blastic phase

               -  Accelerated phase

                    1. Blasts ≥ 15% in blood or BM

                    2. Blasts plus progranulocytes ≥ 30% in blood or bone marrow (BM)

                    3. Basophilia ≥ 20% in blood or BM

                    4. Platelets < 100 × 109/L unrelated to therapy

                    5. Cytogenetic clonal evolution

               -  Blast phase

                    1. ≥ 30% blasts in blood or BM

                    2. Extramedullary disease with localized immature blasts

          4. Adequate end organ function, defined as the following:

               -  Creatinine < 1.5 x upper limit of normal (ULN)

               -  Absolute neutrophil count (ANC) > 1.5 x 109/L

               -  Platelets > 100 x 109/L

               -  Total bilirubin < 1.5 x ULN (Does not apply to patients with isolated
                  hyperbilirubinemia [e.g., Gilbert's disease] grade <3)

               -  Aspartate aminotransferase (AST) (SGOT) and Alanine aminostransferase (ALT)
                  (SGPT) < 3 x ULN

               -  Serum amylase and lipase ≤ 2 x ULN

               -  Alkaline phosphatase ≤ 2.5 x ULN

               -  Patients must have the following laboratory values (WNL = within normal limits at
                  the local institution lab) or corrected to within normal limits with supplements
                  prior to the first dose of study medication:

                    1. Potassium (WNL)

                    2. Magnesium (WNL)

                    3. Phosphorus (WNL)

                    4. Calcium (WNL)

        Exclusion Criteria:

          1. Previous treatment with any other tyrosine kinase inhibitor except for up to 2 weeks
             of nilotinib

          2. Impaired cardiac function including any one of the following:

               -  Inability to monitor the QT interval on ECG

               -  Congenital long QT syndrome or a known family history of long QT syndrome.

               -  Clinically significant resting brachycardia (<50 beats per minute)

               -  Q-T Corrected (corrected Q-T interval) (QTc) > 450 msec on baseline ECG. If QTc
                  >450 msec and electrolytes are not within normal ranges, electrolytes should be
                  corrected and then the patient re-screened for QTc

               -  Myocardial infarction within 12 months prior to starting study Other clinically
                  significant uncontrolled heart disease (e.g. unstable angina, congestive heart
                  failure or uncontrolled hypertension)

               -  History of or presence of clinically significant ventricular or atrial
                  tachyarrhythmias

               -  Complete left bundle branch block

               -  Right bundle branch block plus left anterior/posterior hemiblock

               -  Use of ventricular-paced pacemaker

               -  History of unstable angina within 1 year of study entry

          3. Patients currently receiving treatment with strong CYP3A4 inhibitors and treatment
             cannot be either discontinued or switched to a different medication prior to starting
             study drug. (http://medicine.iupui.edu/clinpharm/ddis/) ).

          4. Patients currently receiving treatment with any medications that have 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 (http://crediblemeds.org/)

          5. Impaired gastrointestinal (GI) function or GI disease that may significantly alter the
             absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting,
             diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).

          6. History of acute pancreatitis within 1 year of study entry or past medical history of
             chronic pancreatitis

          7. Severe and/or uncontrolled concurrent medical disease that in the opinion of the
             investigator could cause unacceptable safety risks or compromise compliance with the
             protocol (e.g. uncontrolled diabetes, uncontrolled infection)

          8. History of another active malignancy within 5 years prior to study entry with the
             exception of previous or concomitant basal cell skin cancer and previous carcinoma in
             situ treated curatively

          9. Known presence of significant congenital or acquired bleeding disorder unrelated to
             cancer

         10. Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered
             from prior surgery

         11. Treatment with other investigational agents within 30 days of Day 1.

         12. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of
             female after conception and until the termination of gestation, confirmed by a
             positive Human chorionic gonadotropin (hCG) laboratory test. Women of child-bearing
             potential, defined as all women physiologically capable of becoming pregnant, unless
             they are using highly effective methods of contraception during the study and for 14
             days after the final dose of nilotinib.