Inotuzumab Ozogamicin and Conventional Chemotherapy In Patients Aged 56 Years and Older With ALL

Inclusion Criteria:

1. Male or female patients, ≥56 years of age and contraindication for age-adaptedconsolidation chemotherapy due to age (≥75 years) and/or severe co-morbidities (>2 perCharlson Score).
2. Newly diagnosed acute lymphoblastic leukemia (>25% marrow blasts, assessed bymorphology; i.e. M3 marrow)
3. Leukemic blasts must have CD22 surface expression of at least 20%, assessed bylocal/institutional flow cytometry of a bone marrow aspirate sample (assessment ofCD22 via the reference lab for immunophenotyping is strongly recommended). In the caseof an inadequate aspirate sample (dry tap), flow cytometry of peripheral bloodspecimen may be substituted if the patient has circulating blasts; alternatively, CD22expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
4. No previous ALL-specific treatment with the exception of corticosteroids and/or singledose vincristine and/or a maximum of three doses of cyclophosphamide (cumulative doseof 600 mg/m2) and the standard prephase treatment
5. With or without documented CNS involvement
6. Adequate liver function, including total serum bilirubin < 2.0 x upper limit of normal (ULN) unless the patient has documented Gilbert syndrome, and aspartate and alanineaminotransferase (AST and ALT) < 2.5 x ULN. If organ function abnormalities areconsidered due to leukemic infiltration of the liver, total serum bilirubin must be < 2.5 x ULN and AST/ALT < 5 x ULN
7. Serum creatinine <1.5 x ULN or any serum creatinine level associated with a measuredor calculated creatinine clearance of >40 mL/min
8. WHO performance status ≤ 2
9. Signed written inform consent
10. Inclusion in GMALL registry

Exclusion Criteria:

1. Philadelphia-chromosome or BCR-ABL positive ALL
2. Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria
3. Peripheral absolute lymphoblast count >10,000/μL after pre-phase treatment and beforestart of study medication
4. Known systemic vasculitis (e.g. , Wegener's granulomatosis, polyarteritis nodosa,systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIVinfection or severe inflammatory disease)
5. Current or chronic hepatitis B or C infection as evidenced by hepatitis B surfaceantigen and anti-hepatitis C antibody positivity, respectively, or knownseropositivity for human immunodeficiency virus (HIV)
6. Major surgery within < 4 weeks before entry on study
7. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function orunstable pulmonary condition)
8. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ ofthe cervix, or localized prostate cancer that has been definitely treated withradiation or surgery; patients with previous malignancies are eligible provided thatthey have been disease free for >2 years
9. Cardiac function, as measured by left ventricular ejection fraction (LVEF) that isless than 45%, or the presence of New York Heart Association (NYHA) stage III or IVcongestive heart failure
10. Myocardial infarction < 6 months before entry on study
11. History of clinically significant ventricular arrhythmia, or unexplained syncope notbelieved to be vasovagal in nature, or chronic bradycardic states such as sinoatrialblock or higher degrees of AV block unless a permanent pacemaker has been implanted
12. Uncontrolled electrolyte disorders that can confound the effects of a QTc prolongingdrug (e.g., hypokalemia, hypocalcemia, hypomagnesemia)
13. History of chronic liver disease (e.g., cirrhosis) or suspected alcohol abuse
14. History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)
15. Administration of live vaccine <6 weeks before entry on study
16. Evidence of uncontrolled current serious active infection (including sepsis,bacteremia, fungemia or COVID-19 infection) or patients with a recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis
17. Patients who have had a severe allergic reaction or anaphylactic reaction to anyhumanized monoclonal antibodies or any known hypersensitivity to the active substanceor any of its excipients
18. Pregnant females; breastfeeding females; males and females of childbearing potential (a woman is considered of childbearing potential (WOCBP) i.e. fertile, followingmenarche and until becoming post-menopausal unless permanently sterile e.g. afterhysterectomy or bilateral ovariectomy. Please refer to chapter 12.4 ContraceptiveRequirements.) not using highly effective contraception or not agreeing to continuehighly effective contraception for women at least 8 months and for men at least 5months after the last dose of investigational product
19. Participation in other studies involving investigational drug(s) (Phase I-IV) within 4weeks before study inclusion
20. Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with study participation orinvestigational product administration or may interfere with the interpretation of studyresults and, in the judgment of the investigator, would make the patient inappropriate forentry into this study.