Adverse event. • The development of toxicity which, in the Investigator’s judgment, precludes further therapy. • Unacceptable adverse event(s). • Intercurrent illness that prevents further administration of treatment . 3. Withdrawal by subject. 4. Lost to follow -up. 5. Non -compliance. 6. At the discretion of the Investigator/physician decision. 7. Death. 8. Pregnancy . 9.