1.1: additions 1.2: revision of the visit schedule 5.1.1: addition of inclusion citeria for the screening phase 6.4: additions about the destruction of study medication 7.1 – 7.4: additions 8.2 – 8.3: additions about the documentation of AE/SAE

- The inclusion criteria were modified at several positions to include the additional molecular marker CD117+. - 2.2: Explanation of the use of the CD117+ marker. - 4.5: The modalities for completion of screening and trial were specified. - 4.6: The timeline was adapted to the current status of recruitment and the end of recruitment/trial date was extended. - 5: The test population and the inclusion criteria were supplemented by the molecular marker CD117+. - 6.1: Linguistic corrections have been made. - 6.2: Side effects have been adapted (supplemented) according to the current SmPC. - 6.6: A passage was added that allows the interruption of the administration of the investigational medication on weekends/holidays for organizational reasons. - 6.7: Dose adjustment is not based on elevated leukocyte levels but on neutrophil levels. -7.1: In the future, buccal smears should also be sent to the laboratory to determine the MRD. -7.2: A note was added that the visits V 0.0 (screening/ inclusion) and V1.0 (start of treatment) should not take place on the same day. - 7.3: The passage that the interruption of the administration of the test medication on weekends/holidays is permitted for organizational reasons has also been inserted here. - 8: The chapter "Translational Research" has been completely added. - 9.1: The definition of Adverese Event was changed from "nachteiliges Vorkommnis" to "medizinisches Vorkommnis". - 9.1: The deadline for reporting events to Celgene was made more specific.

- In general: In some passages, linguistic changes have been made in order to formulate the facts more clearly. Due to the newly added investigations of immunoregulatory and molecular markers and to achieve a high number of evaluable samples, the number of patients was increased to 93 patients in the treatment phase and the recruitment period was extended until December 2017. Among the inclusion criteria, molecular markers t(8;21) and inv16 were deleted. The main changes in the protocol are listed below in chronological order. - Involved persons/ institutions: Personnel changes in the Translational Research Laboratory and Study Coordination were recorded. - 1.1: The necessary examination materials in the context of the initial determination of the molecular marker were defined more precisely, depending on the previous therapy received. - 1.2: Missing visits were added, the procedure after cycle 12 and the exact duration of therapy were specified. -2.3 and 2.4: The background of additional analyses of predictive molecular markers as well as immunomodulatory regulators in translational research is described. - 4.3: Addition of the following investigations in the context of translational research were made: - Frequency of PD-1 on T cells and PD-L1 on blasts, respectively. - Mutation load of selected genes (e.g. DNMT3A, TET2) and their impact on response. - 4.4: In addition to the modulation of T and NK cells, the expression of immune regulators will be monitored under treatment with azacitidine. This will require an additional 40 ml of heparin blood and 10 ml of bone marrow from patients at the time of any hematologic relapse. - 4.5: The number of patients was increased to 93 patients in the treatment phase to achieve a sufficient number of samples for the evaluation of the additional parameters.

- Involved persons/institutions: Personnel changes in the trial management as well as in the laboratory were recorded. - 5.1 and 5.1.1: Study inclusion for patients with CD34+ or CD117+ chimerism in case of allogeneic HSCT was narrowed down to CD34+/CD117+ positivity of blasts of ≥ 10%. - 6.1: The following new indication has been added to the comments on the approval of azacitidine (Vidaza®) according to the current SmPC: Treatment of adult patients 65 years of age and older with AML with > 30% bone marrow blasts who are not suitable for HSCT. - 6.2: Newly reported pyoderma gangraenosum was added to the list of adverse reactions according to the current SmPC for azacitidine (Vidaza®). The adverse reactions reported for the new patient group have also been added to the list. - 7.1: In the flowchart for the patient population qualifying for the RELAZA2 trial, the two molecular markers t(8;21) and inv16 were removed. These were already removed as inclusion criteria in the previous amendment. - 13.1 and 13.2.1: The analysis of the primary endpoint will be conducted with the first 53 treatment patients as initially planned. During the analysis, recruitment will continue to reach the patient numbers (93) for the secondary endpoint analysis. The description of the analysis methods and the further procedure after the primary hypothesis test were completed and described.