Protocol v2.0 19/12/2013 Summary of changes: • Sec on 2.2 ‐ Clarification on how the CD25/71 ADTs will be produced from the starting material. Addition of‐ +2/ day flexibility for when infusing the ATIMP in case d30, 60 or 90 fell on a weekend. Change made throughout protocol. • Sec on 4 ‐ Clarification that only donors for patients randomised to receive the ATIMP will be approached for consent to the trial and confirmation that donors can withdraw up to the point where ADTs are infused into the patient. • Sec on 5.2 ‐ Clarification that starting material will only be obtained by donors if the patient is randomised to receive the ATIMP. • Sec on 7.2.2 ‐ Clarification that if the products do not meet the release criteria, the case will be discussed with the CI, CTC, and manufacturer as it may be in the best interest of the patient to infuse the cells. • Sec on 7.4 ‐ Addition of circulating T cell count >700/μl as an inclusion criteria for consistency reasons. • Sec on 10.2.2 ‐ Clarification that sites must have procedures in place to notify donor collect on centres for a SAR which could be linked to the quality and safety of the donor blood/leucapheresis. Furthermore that the blood collection centre must have systems in place to notify the site of an SAE in a donor which could affect the safety of the patient. This is in line with HTA guidance. • Other typographical changes throughout the protocol, addition of CTA number to the title page, removal of full contact details for the statistician, amending figures to state that the star ng donor material may be donor leucapheresis/blood, minor changes throughout to ensure the protocol is consistent with the new CTC protocol template.

Protocol v3.0 25/11/2014 Summary of changes: • Inclusion Criteria changed from patients with ‘underlying acute myeloid or acute lymphoblastic leukaemia’ to patients with ‘underlying haematological malignancy’ • EBV and CMV serology added to the screening assessments for patients • ‘+/2 working days’ changed to ‘+/7 days’ when referring to the infusion schedules (D30, D60 and D90 posttransplant) • Clarification that any delays to ATIMP infusion for clinical reasons need to be agreed in advance with the trials office. • Addition that surplus ATIMP (CD25/71 ADTs) may be stored at the manufacturing site for use in future ethically approved research related solely to ICAT, following obtaining patient and donor consent. • Removal of the list of ‘expected adverse events’ following allodepleted donor T cell infusion, as they are no longer exempt from SAE reporting.

Protocol 4.0 17/12/2015 NOTE: this amendment was approved by both REC and MHRA but MRC in their role as funder did not approve, therefore this amendment was not implemented at sites and the latest document versions in use before the submission of the amendment remained in use.

Protocol v5.0 04/05/2016 Summary of changes: • ‘+/- 7 days’ changed to ‘+/- 10 days’ when referring to the infusion schedules (D30, D60 and D90 posttransplant). • "A minimum of 25 days should be given between consecutive doses to ensure no GVHD has developed" has been added throughout for clarification in light of the above change

Protocol v6.0 12/12/2016 The trial protocol was amended to clarify that it is not always possible for the laboratory to manufacture enough allodepleted donor T cells for the patient to be able to receive 3 doses of the ATIMP. In such cases, after discussion with the patient, only 1 or 2 doses may be administered (depending on the number of cells manufactured). The last substantial amendment approved by the ethics committee on 04/10/2016 amended the patient information sheet to account for this but it was omitted from the trial protocol in error. The randomisation section was amended to outline that patients on both the ATIMP arm and control arm of the trial should receive a patient contact card to ensure the trial adheres to good clinical practice guidelines for advanced therapies. The statistics section was amended so that the predicted dropout rate has been changed from 35% to 50% and the potential target recruitment total amended from 32 to 50 patients to account for this. This has been done as the dropout rate was greatly underestimated and the current recruitment total is 26 patients. The target treatment total remains at 24 patients but recruitment is expected to run until July 2017 and so it is likely that the trial will meet the target recruitment total before meeting the target treatment total. Therefore, this has been amended to allow for the original target treatment total to be met even if the original estimated target recruitment total is surpassed.

Protocol v7.0 12/07/2017 Summary of changes: 1. Twelve month extension to recruitment from 3 to 4 years (section 1.1’Summary of Trial Design’) 2. Section 15.1 ‘Sample size calculation’ now clarifies that once the required 8 patients in the control arm reach 4 months (primary end point assessment), any remaining patients will be registered into the ATIMP arm until the target of 16 treated ATIMP patients is achieved and the trial will close to recruitment. In addition the following clarifications regarding the serology tests required to be performed at screening have been added to sections 5.1 ‘Pre-randomisation evaluation’ and 5.3.2 ‘Exclusion Criteria’ (no new tests have been added): • results from HBV, HCV, syphilis and HIV tests are required prior to randomisation of patient into the study to assess eligibility, while EBV, CMV and HTLV results are needed for information • patients with ‘active’ HBV, HCV and HIV infection are excluded from the trial and PCR should be used to rule out ‘active infection’ if serology result is positive.