If gemcitabin e is delayed, GM -CSF/TG01 should be continued as planned. If gemcitabine treatment is stopped, GM -CSF/TG01 may continue as described in section 3.1. If no instructions are available, the following guidelines can be followed: Table 4: Gemcitabine dose delay/reduction guidelines Absolute granulocyte count (x 10 6/L) Platelet count (x 10 6/L) % of full dose ≥1000 And ≥100,000 100 500-999 Or 50,000-99,999 75 <500 Or <50,000 Hold 5-FU and Leucovorin Institutions should follow the manufacturer’s instructions for dosing modification for the country in which the study is being conducted. If 5-FU and Leucovorin are delayed, GM -CSF/TG01 should be continued as planned. If 5-FU and Leucovorin treatment is stopped, GM -CSF/TG01 may continue as described in section 3.1. CT TG01 -01 Version v 10.0 27 June 2018 Confidential 58 / 87 If no instructions are available, the standard procedure at the institution for reduction of 5-FU/Leucovorin should be followed 4.5.3 GM-CSF /TG01 dose interruption If a patient experiences GM-CSF or TG01 related toxicity on the days of the scheduled GM-CSF/TG01 injections, GM-CSF/TG01 should be delayed until toxicity resolved to CTC grade 1. The patient should then restart at the next planned visit. Chemotherapy should be continued as planned as long as chemotherapy prescribing i nformation requirements are fulfilled . Management of TG01 or GM- CSF related reaction s: • All groups: At any time during the vaccination schedule – if a patient exhibits signs of an allergic reaction (not just a local reaction) then they should be treated symptomatically and for all subsequent TG01 administrations they should be pre- medicated with intravenous antihistamine treatment ( e.g. chlorpheniramine or dexchlorpheniramine ) 30 minutes before either the DTH injection (TG01 alone) when done before vaccination or before vaccination (i.e. before the GM -CSF injection which is followed by the TG01 10- 15 minutes later in the main group or concomitant group or 15-20 minutes later in the modified vaccination group) • Main group and concomitant group ONLY : For patients who have completed/finished chemotherapy – All TG01 administrations should be preceded by intravenous antihistamine treatment as above • All groups: Patients who have local reactions only – It is permissible to use topical therapies such as anti -histamine or steroid creams or EMLA cream for pain • All groups: Where a DTH injection is being performed the TG01 DTH dose should be administered 30 minutes before the GM -CSF/TG01 administration and patients should be observed for at least 30 minutes after ALL GM -CSF/TG01 administration • All groups: I n patients who have not had prophylaxis o If after the TG01 DTH dose the patient exhibits a Grade 1 or 2 allergic reaction then the GM-CSF/TG01 administrations should be delayed and the patient given intravenous antihistamine treatment as above o If a Grade 3 or 4 reaction occurs then no more vaccinations should be given and the patient withdrawn from TG01 treatment; if the patient is still receiving chemotherapy then this should continue per schedule. • All groups: In patient s who have had prophylaxis o If after the DTH dose the patient exhibits a Grade 1 reaction then the GM-CSF/TG01 administrations should only be given if the investigator believes it is reasonable to do so based on the nature of the reaction o If a Grade ≥2 re action occurs then no more vaccinations should be given and the patient withdrawn from TG01 treatment (and continue chemotherapy if this has not been completed) • All groups: Patients who are to receive no more vaccinations due to an allergic reaction but have exhibited a positive immune response may continue in the study until completion or earlier if the investigator feels that this is appropriate • All groups: Precautions should be in place in case of anaphylaxis CT TG01 -01 Version v 10.0 27 June 2018 Confidential 59 / 87 4.6 Concomitant medication No systemic anti- cance r therapy other than gemcitabine or 5 -FU/Leucovorin is to be used during the trial before recurrence of the disease. After recurrence, for patients who have an immune response, the standard of care can be used according to the investigational site’s usual practise. Other vaccination must not be administered during the Initial treatment period ( until week 1 1 for the main group, week 13 for the concomitant group and week 8 for the modified vaccination group) and should be avoided if possible for the rest of the study duration. Vaccination with yellow fever or live (attenuated) vaccines is prohibited until at least 3 months after the last chemotherapy administration. Any agent with a known effect on the immune system should be excluded before recurrence, unle ss it is being given at dose levels that are not immunosuppressive, e.g.