International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 (IntReALL BCP 2020)

For all study questions: * Confirmed diagnosis of 1st relapsed B-cell precursor ALL * Patients ≥ 1 year and less than 18 years of age at diagnosis of primary ALL and less than 21 years of age at date of inclusion into the study * Patient enrolled in a participating center * Written informed consent (IC) * Start of treatment falling into the study period * No participation in other clinical trials 30 days prior to study enrolment that interfere with this protocol, except trials for primary ALL Specific for SR induction randomization: * Meeting SR criteria * BM involvement (≥ 5% or ≥ 1% leukemic blasts confirmed by 2 quantitative methods) * CD22 positive ALL (\>80% confirmed by flow-cytometry) * No previous history of veno-occlusive disease (VOD)/ sinusoidal obstruction syndrome (SOS) Specific for SR MRD poor response consolidation: * Meeting SR criteria with bone marrow involvement at relapse diagnosis * M1/CR2 and MRD ≥ 10-4 after induction * CD19 positive ALL at relapse (\>10%) Specific for SR MRD good response consolidation: * Meeting SR criteria with bone marrow involvement at relapse diagnosis * M1/CR2 and MRD \< 10-4 after induction * CD19 positive ALL at relapse (\>10%) Specific for HR consolidation arm * Meeting HR or VHR (in case of no possibility to be treated with CAR T cells) criteria * M1/CR2 after induction therapy * CD19 positive ALL at relapse (\>10%) Specific for IEM arm: * Histology or cytology proven extramedullary relapse * No bone marrow involvement (M1 at relapse diagnosis) and bone marrow MRD \<1% * CD19 positive ALL at relapse (\>10%)

* Known hypersensitivity to the active substances or excipients of the IMP's or the SOC drugs, except to PEG-asparaginase which can be replaced by Erwinase * Left ventricular ejection fraction (LVEF) \< 50% or fractional shortening \< 25%, and/or current or prior treatment for cardiomyopathy and/or history of clinically significant arrhythmias * Pregnancy or positive pregnancy test in female patients (urine sample positive for β-HCG \> 10 U/l) at screening or within 7 days prior to the initiation of study treatment * Sexually active adolescents and adults not willing to use highly effective contraceptive method (pearl index \<1) until 12 months after end of anti-leukemic therapy * Women not willing to refrain from breast feeding until 12 months after end of anti-leukemic therapy * Relapse post allogeneic HSCT * Relapse post chimeric antigen receptor T-cell (CAR-T) therapy * The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian * Objection to the study participation by a minor patient * Patients in a dependent or subordinate relationship to the investigator or site staff (e.g. employees, relatives, or students) * No consent is given for saving and propagation of pseudonymized medical data for study reasons * Patients with any concurrent medical condition, laboratory abnormality, concomitant treatment, or comorbidity that, in the investigator's clinical judgment would * compromise the patient's ability to safely receive or tolerate inotuzumab ozogamicin and/or blinatumomab * significantly interfere with assessment of treatment efficacy or safety * make it unlikely that the patient would derive clinical benefit from protocol therapy * preclude adherence to study procedures or follow-up requirements * Subjects unwilling or unable to comply with the study procedures * Subjects who are legally detained in an official institute Specific for SR induction randomization: * Prior confirmed severe (grade 3 or 4) or ongoing VOD/SOS * Serious ongoing hepatic disease (e.g., cirrhosis, active hepatitis) not related to the current ALL relapse or current diagnostic/therapeutic measures * ALT \> 2,5 x ULN (at relapse diagnosis before start of cytoreduction) and/or bilirubin \> 1.5 x ULN * Patients with intolerance to PEG-asparagniase and also to Erwinase are stratified to the inotuzumab arm * Patients with insufficient expression of CD22 (\< 80%) on leukemic blasts, they are assigned to the control chemotherapy arrm Specific for blinatumomab treatment: * Clinically relevant CNS pathology requiring treatment (eg, unstable epilepsy) * Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully treated prior to enrollment Allowed systemic diseases and concomitant medication * Patients with Down Syndrome (DS) can be included as separate and descriptive population, not joining the study questions. Those with BM involvement receive inotuzumab ozogamicin for induction without randomization. HR patients and SR patients with MRD poor response will be allocated to allo-HSCT indication, or in case CD19 directed CAR-T-cell therapy off-protocol as individualized treatment approach. Patients with MRD good response will get the SR consolidation and maintenance therapy. Those with IEM profile will be treated according to the IEM stratum. Patients not expressing sufficiently CD22 and/or CD19 will receive the respective chemotherapy strategy. * Patients with BCR::ABL positive (Ph+) or BCR::ABL like (Ph-like) BCP ALL with TKI treatment option can be included as separate and descriptive population, not joining the study questions. Those with BM involvement receive inotuzumab ozogamicin plus TKI (investigators choice) without randomization for induction followed by HC1 and blinatumomab plus TKI followed by allo-HSCT. Those with IEM profile will be treated according to the IEM stratum plus TKI. Patients not expressing sufficiently CD22 and/or CD19 will receive the respective chemotherapy strategy. * Patients with systemic diseases such as cystic fibrosis or diabetes may be eligible for enrolment in this study only if they presumably will tolerate the protocol treatment and primary dose reductions would not be necessary. * Any kind of concomitant medication given due to medical reasons is allowed. Incompatibilities and drug interactions with the study medications are listed in the appendix. In case of expected adverse interactions, concomitant therapies should be changed to alternative less problematic agents if possible Prohibited medication * Antileukemic therapy other than scheduled in the protocol (except cytoreductive pre-phase with dexamethasone) * Investigational drugs other than scheduled in the protocol * Attenuated live vaccines which are strictly prohibited during and until 6 months after end of chemotherapy or 18 months after allo-HSCT