6. DOSING DELAYS/DOSE MODIFICATIONS All toxicity associated with prio r treatment must resolve to grade 1 or less off steroid treatment for at least 2 weeks. Patients who have discontin ued treatment for pulmonary, renal or neurologic toxicity or who have experienced grade 4 t oxicity should not be enrolled in the study. All related toxicities will be revi ewed by the protocol P.I., participating site P.I.s, CTEP and the CITN Coordinating Center for an indicat ion to change the dosing schedule. The selected doses of INCB024360 and MELITAC 12.1 have been established as having excellent safety profiles. Dose escalation is not planned or necessar y. However, when used together, unexpected toxicities might occur. Thus , rules for stopping will be incorporated in the event that dose-limiting AEs are observed. Toxicities for each agent will be monitored co ntinuously and will be graded by the NCI CTCAE v4.0 with stopping rules for AEs. At the discretion of the investigators, treatment may be held for up to 14 days to permit the evaluation or resolu tion of symptoms that may be unrelated to treatment but may affect patient safety (e.g., influenza, minor trauma). DLT’s include all Grade 3 AEs regardless of inve stigator attribution or relatedness except for expected grade 3 injection site reactions. ( section 5.5) Based on investigator determination the following Grade 3 toxicities can be deemed non-DLT: • adverse event with a clear alternative explana tion (e.g. due to disease progression) • transient toxicities ( ≤72 hours) • injection site reactions that are expected and do not requir e any surgical intervention or repair NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 36 • abnormal laboratory values without associated clinically signif icant signs or symptoms There are two exceptions to the above: Grade 1 or greater ocular toxicities will be considered a DLT. Grade 2 LFT elevations will be considered a DLT. In the event of a DLT, it w ill be determined by the safety team whether both the INCB024360 AND the MELITAC 12.1 will be permanently discontinued. Vitiligo will not be considered a DLT. Pages 33, 34 and 35 include tables for some of th e more common AE’s including instructions for handling. For any AE’s not listed in these tables, proceed in the following manner: Grade 1 and Grade 2: Continue to monitor, follow and grade these adverse events. Grade 3: Stop Protocol Therapy in cluding both INCB024360 and MELITAC 12.1 Grade 4: Stop Protocol Therapy in cluding both INCB024360 and MELITAC 12.1 In addition, treatment will be discontinued for (a) Any DLT, (b) disease progression requiring other therapy, (c) noncompliance with study requirem ents, (d) other safety considerations in the judgment of the investigator , or (e) patient request. The treatment regimen will be considered safe as long as the number of participants experiencing a treatment-related AE (DLT) does not exceed 33%. If more than 33% of patients accrued are known to have experienced a treatment-related DLT, the study will be closed to further accrual, except that 1 treatment related DLT observed out of the first 3 patients accrued will be acceptable and will not result in the closing of the study. Nausea Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 Off Protocol Therapy Off Protocol Therapy Grade 4 Off protocol therapy Off protocol therapy Recommended management: antiemetics Vomiting Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 Off Protocol Therapy Off Protocol Therapy Grade 4 Off protocol therapy Off protocol therapy Recommended management: antiemetics Investigations (Liver Function Tests ALT + AST) Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 < Grade 1 No change in dose No change in dose Grade 1* No change in dose No change in dose NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 37 Investigations (Liver Function Tests ALT + AST) Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 Grade 2 Off Protocol Therapy Off Protocol Therapy Grade 3 or 4 Off Protocol Therapy Off Protocol Therapy *For Grade 1 LFT Elevations, increase LFT monitoring to twice weekly. Diarrhea Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 Off Protocol Therapy Off Protocol Therapy Grade 4 Off protocol therapy Off protocol therapy Recommended management: physician discretion Neutropenia Management/Next Dose forINCB024360Management/Next Dose forMELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 Off Protocol Therapy Off Protocol Therapy Grade 4 Off protocol therapy Off protocol therapy Recommended management: treatment of infection as appropriate Thrombocytopenia Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 Off protocol therapy Off protocol therapy Grade 4 Off protocol therapy Off protocol therapy Recommended management: platelet transfusions if indicated Fatigue Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 or Grade 4 Off Protocol Therapy Off Protocol Therapy Recommended management: physician discretion Ocular Toxicity Management/Next Dose for INCB024360Management/Next Dose forMELITAC 12.1 ≤ Grade 1 Off protocol therapy* Off protocol therapy Grade 2 Off protocol therapy Off protocol therapy Grade 3 Off protocol therapy Off protocol therapy Grade 4 Off protocol therapy Off protocol therapy *Defined as treatment-related grade 1 ocular toxicities NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 38 Chills/fever/malaise following immunization Management/Next Dose for INCB024360Management/Next Dose for MELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 Off protocol therapy if fails to resolve by the next scheduled immunizationOff protocol therapy if fails to resolve by the next scheduled immunization Grade 4 Off protocol therapy Off protocol therapy Injection site reaction Management/Next Dose forINCB024360Management/Next Dose forMELITAC 12.1 ≤ Grade 1 No change in dose No change in dose Grade 2 No change in dose No change in dose Grade 3 No change in dose* No change in dose** Grade 4 Off protocol therapy Off protocol therapy *See section 5.2 ** MELITAC 12.1 vaccine may be given if the grade 3 injection site reaction co mbined area of skin ulceration is <2 cm 6.1 Delayed Visits for Reason s Other Than Toxicity A schedule for return visits shou ld be established at the first visit. If a participant misses a vaccination, the missed treatment will be admini stered as soon as possible, so that the subsequent vaccinations are given in the appropriate intervals.