Venetoclax in Addition to Blinatumomab in Adult Patients With Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL)

Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutionalguidelines. The patient must provide informed consent prior to the first screeningprocedure

2. Age ≥ 18 years

3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

4. Availability of patient-specific molecular MRD markers of immunoglobulin/T-cellreceptor gene rearrangementsas assessed by PCR with a sensitivity of at least 10E-04

5. Diagnosis of Philadelphia negative, CD19-positive B-precursor acute lymphoblasticleukemia according to WHO classification:

• Refractory BCP-ALL to primary induction therapy, including at least threecycles of standard chemotherapy

• Untreated first relapse of BCP-ALL with first remission duration < 12 months or

• Second or greater relapse of BCP-ALL or refractory relapse or

• Relapse of BCP-ALL any time after allogeneic HSCT or

6. Positivity of MRD marker of immunoglobulin/T-cell receptor gene rearrangements ofgreater than 0.01% if in first or second remission of BCP-ALL

7. Negative pregnancy test < 7 days before first study drug in women of childbearingpotential, defined as all women physiologically capable of becoming pregnant, unlessthey fulfil at least one of the following criteria:

8. Post-menopausal (i.e. 12 months of natural amenorrhea or 6 months of amenorrheawith Serum FSH > 40 U/ml

9. Post-operative after bilateral ovariectomy with or without hysterectomy

10. Continuous and correct application of a contraception method with a Pearl indexof < 1% (e.g. implants, depots, oral contraceptives, intrauterine device) frominitial study drug administration until at least 3 months after the last doseof study drug. A hormonal contraception method must always be combined with abarrier method (e.g. condom)

11. Sexual abstinence

12. Vasectomy of the sexual partner

13. Ability to understand and willingness to sign a written informed consent

14. Willingness to participate in the registry of the German Multicenter Study Group forAdult ALL (GMALL)

Exclusion Criteria:

1. Patients with diagnosis of Philadelphia positive BCP-ALL according to WHOclassifiation

2. Patients with diagnosis of Burkitt´s Leukemia according to WHO classification

3. Patients with extramedullary relapse; non-bulky lymph node (< 7.5 cm diameter)involvement will be accepted

4. Patients with CNS involvement at relapse (as determined by CSF analysis)

5. Patients with suspected or histologically confirmed testicular involvement atrelapse

6. Current autoimmune disease of any kind or history of autoimmune disease withpotential CNS involvement

7. Patients with Philadelphia-positive BCP-ALL still receiving TKI

8. Prior or concomitant therapy with BH3 mimetics

9. Prior therapy with anti CD19 therapy, unless administered in MRD-positive setting (i.e. with bone marrow blasts ≤ 5%)

10. Treatment with any of the following within 7 days prior to the first dose of studydrug: strong cytochrome P450 3A (CYP3A) inhibitors, moderate or strong CYP3Ainducers

11. Intake of any of the following within 3 days prior to the first dose of study drug:grapefruit, grapefruit products, Seville oranges or star fruit

12. Presence of Graft-versus-Host Disease (GvHD) and/or on immunosuppressant medicationwithin 2 weeks before start of protocol-specified therapy

13. Radiation, chemotherapy (with the exception of prephase therapy), or immunotherapyor any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1 orradio-immunotherapy 4 weeks prior to Cycle 1 Day 1.

14. Major surgery within 2 weeks of first dose of study drug

15. Patients who are pregnant or lactating

16. Any life-threatening illness, medical condition or organ system dysfunction which,in the investigator's opinion, could compromise the patient's safety

17. Unstable cardiovascular function:

• Symptomatic ischemia, or

• Uncontrolled clinically significant conduction abnormalities (1st degree AVblock or asymptomatic LAFB/RBBB will not be excluded), or

• Congestive heart failure (CHF) of NYHA Class ≥3, or

• Myocardial infarction (MI) within 3 months

18. Evidence of clinically significant uncontrolled condition(s) including, but notlimited to: Uncontrolled and/or active systemic infection (viral, bacterial orfungal), chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiringtreatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e.hepatitis B surface (HBs) antigen negative-, anti- HBs antibody (anti-HBs) positiveand anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibodyfrom intravenous immunoglobulins (IVIG) or blood transfusions may participate.

19. Known human immunodeficiency virus (HIV) infection (HIV testing is not required)

20. Patients unable to swallow tablets, patients with malabsorption syndrome, or anyother GI disease or GI dysfunction that could interfere with absorption of studytreatment

21. Adequate hepatic function per local laboratory reference range as follows: Aspartatetransaminase (AST) and alanine transaminase (ALT) < 3.0X ULN, Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)

22. Severe renal dysfunction: estimated creatinine clearance of < 20 mL/min, measured in 24 hour urine or calculated using the formula of Cockroft and Gault

23. History or presence of clinically relevant CNS pathology such as epilepsy, childhoodor adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia,Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.History of CNS leukemia that is controlled at relapse may be enrolled in this study.

24. History of malignancy other than ALL within 5 years prior to start ofprotocol-specified therapy with the exception of:

• Malignancy treated with curative intent and with no known active diseasepresent for 2 years before enrollment and felt to be at low risk for recurrenceby the treating physician including

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidenceof disease

• Adequately treated cervical carcinoma in situ without evidence of disease

• Adequately treated breast ductal carcinoma in situ without evidence of disease

• Prostatic intraepithelial neoplasia without evidence of prostate cancer.

25. Current autoimmune disease or history of autoimmune disease with potential CNSinvolvement

26. Live vaccination within 2 weeks before the start of study treatment

27. Known hypersensitivity to immunoglobulins or to any other component of the studydrug formulation

28. Subject has known sensitivity to immunoglobulins or any of the products orcomponents to be administered during dosing.

29. Currently receiving treatment in another investigational device or drug study orless than 30 days since ending treatment on another investigational device or drugstudy(s). Thirty days is calculated from day 1 of protocol-specified therapy

30. Subject likely to not be available to complete all protocol-required study visits orprocedures, including follow-up visits, and/or to comply with all required studyprocedures to the best of the subject's and Investigator's knowledge.

31. History or evidence of any other clinically significant disorder, condition ordisease (with the exception of those outlined above) that, in the opinion of theinvestigator would pose a risk to subject safety or interfere with the studyevaluation, procedures or completion.

32. Woman of childbearing potential, defined as all women physiologically capable ofbecoming pregnant, unless they fulfil at least one of the following criteria:

• Post-menopausal (i.e. 12 months of natural amenorrhea or 6 months of amenorrheawith Serum FSH > 40 U/ml

• Post-operative after bilateral ovariectomy with or without hysterectomy

• Continuous and correct application of a contraception method with a Pearl indexof < 1% (e.g. implants, depots, oral contraceptives, intrauterine device) frominitial study drug administration until at least 3 months after the last doseof study drug. A hormonal contraception method must always be combined with abarrier method (e.g. condom)

• Sexual abstinence

• Vasectomy of the sexual partner

33. Male who has a female partner of childbearing potential, and is not willing to use 2highly effective forms of contraception while receiving protocol-specified therapyand for at least an additional 3 months after the last dose of protocol-specifiedtherapy