Amendment N°1, applicable in all countries, mainly concerned: - Modification of the definitions of “Criteria for defining toxicity”. - Removal of inclusion criterion n°8 requesting the patients to consent in the same time to their participation to the parent study and to the LTFU study and addition of an exclusion criterion (criterion n°34) for patients who were unable or unwilling to undergo a safety follow-up for 15 years. - Clarification regarding the maximum amount of blood to be taken from participants. Reduction in time interval between inclusion of the 3rd and the 4th patient and thereafter between inclusion of 2 consecutive patients within a group of 3 patients. - Addition of a communication plan between sponsor and sites. - Addition of exclusion criteria n° 33 (patients tested positive for HIV). - Clarification regarding exclusion criteria n°11 (reduction of the washout period required after the use of previous treatment). - Addition of reporting of CD52 expression data on leukemic cells as exploratory objective.

Amendment N°2, applicable in all countries, mainly concerned: - Clarification of AEs to be reported during the FU period and deletion of Appendix 2. - Several modifications to be consistent with the safety changes implemented in the CALM protocol following Food and Drug Administration request and NIH recombinant DNA advisory Committee: * Modification of the definitions of “Criteria for defining toxicity”. * Use of the grading of Harris (Harris et al, 2016) for grading scale for GvHD. * Update on the management of safety risks and supportive care measures; addition of appendices “CRS management” and “neurotoxicity management”. * Addition of ineligibility criteria for using alemtuzumab in LD regimen. * Addition of discontinuation criteria for using alemtuzumab in LD regimen. * Recommendation for antimicrobial surveillance/prophylaxis for opportunistic infections (viral, fungal, bacterial) until blood count recovery for patients receiving alemtuzumab. * Addition of one blood sample for potential retrospective genomic analysis in case of T-cell transformation, at D0, D84, M6 and M12. * Addition of immunogenicity assays (human anti-UCART19 antibodies) at D0, D28, D84 and M12. - Rewording of exclusion criteria n° 24 to define more specifically an active infection. - Addition of eligibility criteria before UCART19 administration in the study plan. - Modification of the exclusion criteria n°33 with the exclusion of patients tested positive for HTLV at inclusion. - Addition of IL4 in the list of parameters to be dosed among the cytokines. - Reporting in the eCRF of data on CD52 expression on leukemic blasts (on blood or bone marrow if assessments were performed locally).

Amendment N°3, applicable in all countries, mainly concerned: - To discontinue the use of alemtuzumab following DSMB recommendation. - To modify the doses of fludarabine-cyclophosphamide used as part of LD regimen. - To implement the request received from the ANSM after the submission of PALL and CALM protocols: - Addition of the inclusion criterion n°35 (list of biological parameters and clinical parameters with limit values to be checked). - Deletion of the exclusion criterion n°23 (“Unstable cardiovascular disease”, replaced by clinical parameters of cardiac function as part of the inclusion criterion n°35). - Addition of the exclusion criterion n°36 (“Any known contraindication to any of the drugs that will be used for the lymphodepletion (fludarabine, cyclophosphamide) or other drugs proposed for safety issues (including tocilizumab, rituximab)”). - Addition of a neurological consultation (mandatory for France and according to local practices for other countries) during the screening period. - Addition of cytoreduction decision criteria. - Addition of an immunoglobulin assay at D14 (if required). - Update of paragraph on neurotoxicities and its corresponding appendix. - Update of appendix “CRS mitigation and management”.

Amendment N°4, applicable in all countries, mainly concerned: - To remove the planned allo-HSCT from the study protocol, with update of study objectives. - To add the possibility of an optional UCART19 re-dosing after the initial UCART19 infusion. - To modify the study duration from 15 months to 12 months and to modify the study plan with the definition of treatment and follow-up periods. - To add 8 participants (up to 18 participants) and consequently to modify the stopping rules and to define the enrolment strategy from the 10th patient. - To clarify the safety risks (CRS, neurologic toxicity and genotoxicity and tumorigenicity). - To add a new safety identified risk, prolonged cytopenia. - To add “prolonged cytopenia” as new AESI to be considered during the treatment period. - Addition of an eligibility criterion n°44 “Availability of a donor for potential allo-HSCT in the event of persistent marrow aplasia without evidence of residual leukaemia”.

Amendment N°6, applicable in all countries. The main objective of this amendment was to re-introduce the use of alemtuzumab in the lymphodepletion regimen following DSMB recommendation. Accordingly, the following changes were applied: - Re-introduction of ineligibility criteria and stopping rules for alemtuzumab administration. - Modification of the doses of fludarabine and cyclophosphamide when administered in combination with alemtuzumab. - Modification of exclusion criteria n°36 to include alemtuzumab. - Modification of treatment authorized to include methylprednisolone and surveillance/prophylaxis measures in case of alemtuzumab use. - Modification of safety risks and supportive care measures for infection in case of alemtuzumab use. - Update of assessment of safety to include the addition of surveillance/prophylaxis measures in case of alemtuzumab use in viral/bacterial/protozoal work-up.

Amendment N°8, applicable in all countries. The main objectives of this substantial amendment were: - To modify some inclusion and exclusion criteria in order to address a high unmet medical need for some categories of patients: - Update of inclusion criterion n°2 with the inclusion of patients from birth. - Addition of inclusion criterion n°60 (no detectable anti-CD19 CAR transgene copies in blood, by qPCR, in patients previously treated with CAR T cell therapy). - Update of exclusion criterion n°10 (with the addition of the exception “autologous CAR-T cell therapy”). - Addition of exclusion criterion n°61 (known history of CRS grade 4 related to previous CAR T cell therapy). - Removal of exclusion criterion n°14 (weight below 8.8 kg). - Update of exclusion criterion n°16a (with exclusion of patients with allogeneic HSCT within 3 months prior to screening instead of 6 months). - Update of exclusion criterion n°29 (which became “known history of irreversible severe neurological toxicity related to previous antileukemic treatment leading to organic central nervous system lesions”). - To update the dose of CD19CAR/RQR8+_TCRαβ-_T-cells/kg resulting from the weight band dosing calculation.

Amendment N°9, applicable in all countries. The main objectives were: - To modify LD regimen schedule: start lymphodepletion at D-4 and modifications of doses of cyclophosphamide and alemtuzumab. - To modify some exclusion/inclusion criteria: update of inclusion criteria 35a, 38a, 53a with serum ALT/ AST ≤ 5 times ULN instead of 3 times ULN; update of inclusion criterion n°60 with the addition of B cells recovery as surrogate demonstrating the loss of CAR T cells persistence and update of exclusion criterion n°59 to allow use of corticosteroids in combination with alemtuzumab at D-4 and D-3. - To modify eligibility criteria for UCART19 (re)-administration: deletion of criteria 41a and 56 concerning disease progression after lymphodepletion. - To clarify the use of alemtuzumab: update of the use of alemtuzumab as non-optional, update of the stopping rules for the use of alemtuzumab and addition of exclusion criteria related to use of alemtuzumab (criterion n°62). - To allow re-dosing possibility from D14 instead of D28 (update of criteria n°46 and 47). - And to update AESI immediate reporting rules (only severe and/ or serious events to be notified immediately).