Clinical trial NCT01602952 (phase 1/phase 2, status: completed)
Conditions: leukemia, leukemia, myeloid, leukemia, myelogenous, chronic, bcr-abl positive, philadelphia chromosome, hematologic diseases
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C92.Z1, C92.Z2, C92.91, C92.92, C92.Z0, C92.90, C92.11, E70.338, E70.339, P09.3, O28.0, P61.8, P61.9, T45.8X1A
Drugs: radotinib
SMILES: CC1=CN(C=N1)C1=CC(NC(=O)C2=CC=C(C)C(NC3=NC=CC(=N3)C3=CN=CC=N3)=C2)=CC(=C1)C(F)(F)F
Eligibility criteria:

        Inclusion Criteria:

        Phase I

          1. Age ≥ 18 years old

          2. Ph+ CML patients who are resistant at chronic, accelerate, and acute phase, or
             suboptimal responsive, or intolerant to imatinib or resistant or intolerant to at
             least one second-generation targeted anticancer agent while being resistant,
             suboptimal responsive, or intolerant to imatinib simultaneously.

          3. WHO Performance status of ≤2

          4. Patients must have the following laboratory values With normal liver and renal
             function

          5. Patients who have received interferon, other anti cancer drug or radiotherapy > 1 week
             prior to starting study drug.

        Phase II

          1. Age ≥ 18 years old

          2. Ph+ CML patients in chronic or accelerated phase who are resistant or intolerant to
             Imatinib mesylate

          3. WHO Performance status of ≤2

          4. Patients must have the following laboratory values With normal liver and renal
             function

          5. Patients who have received interferon, other anti cancer drug or radiotherapy > 1 week
             prior to starting study drug.

        Exclusion Criteria:

        Phase I

          1. CNS infiltration

          2. Impaired cardiac function, including any one of the followings.

               -  LVEF <45% as determined by MUGA scan or echocardiogram

               -  Clinically significant resting bradycardia

          3. Severe GI disease that may cause drug absorption problem of study drug

          4. Use of therapeutic Warfarin

          5. Acute or chronic liver or renal disease

          6. Other concurrent severe and/or uncontrolled medical conditions

          7. Treatment with any hematopoietic colony-stimulating growth factors ≤1 week prior to
             starting study drug.

          8. Patients who are currently receiving treatment with medications have the potential to
             prolong the QT interval

          9. Patients who have received Imatinib, interferon, other anti cancer drug or
             chemotherapy ≤ 1 week

         10. Patients who have received Nilotinib and Dasatinib ≤4 weeks prior to starting study
             drug.

         11. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or
             who have not recovered from side effects of such therapy

         12. Patients who are pregnant or breast-feeding or adults of reproductive potential not
             employing an effective method of birth control.

         13. Patients not to agree using birth control during the study and for up 3 months
             following study completion.

        15. HIV infection

        Phase II

          1. Blast phase CML

          2. CNS infiltration

          3. Impaired cardiac function, including any one of the following

               -  LVEF< 45% as determined by MUGA scan or echocardiogram

               -  Use of Cardiac pacemaker

               -  ST depression > 1mm in 2 or more leads and/or T wave inversions in 2 or more
                  contiguous leads

               -  Congenital long QT syndrome

               -  History of, or presence of significant ventricular or atrial tachyarrhythmias

               -  Clinically significant resting bradycardia

               -  QTcF> 480 msec on screening ECG

               -  Right bundle branch block + left anterior hemiblock, Bifascicular block

               -  Angina pectoris

          4. Severe GI disease that may cause drug absorption problem of study

          5. Use of therapeutic Warfarin

          6. Acute or chronic liver or renal disease

          7. Other concurrent severe and/or uncontrolled medical conditions

          8. Treatment with any hematopoietic colony-stimulating growth factors ≤1 week prior to
             starting study drug.

          9. Patients who are currently receiving treatment with medications have the potential to
             prolong the QT interval

         10. Patients who have received Imatinib, interferon, other anti cancer drug or
             chemotherapy ≤ 1 week

         11. Patients who have received wide field radiotherapy ≤4 weeks prior to starting study
             drug.

         12. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or
             who have not recovered from side effects of such therapy

         13. Patients who are pregnant or breast-feeding or adults of reproductive potential not
             employing an effective method of birth control