Acute lymphoblastic leukemia, Philadelphia-chromosome and BCR-ABL negative disease, patient aged 56 years or older MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: BESPONSA
Product Name: Inotuzumab Ozogamicin
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
Sponsors
Goethe Universität
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients, =56 years of age and contraindication for age-adapted consolidation chemotherapy due to age (=75 years) and/or severe co-morbidities (>2 per Charlson Score). 2. Newly diagnosed acute lymphoblastic leukemia (>25% marrow blasts, assessed by morphology; i.e. M3 marrow) 3. Leukemic blasts must have CD22 surface expression of at least 20%, assessed by local/institutional flow cytometry of a bone marrow aspirate sample (assessment of CD22 via the reference lab for immunophenotyping is strongly recommended). In the case of an inadequate aspirate sample (dry tap), flow cytometry of peripheral blood specimen may be substituted if the patient has circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen 4. No previous ALL-specific treatment with the exception of corticosteroids and/or single dose vincristine and/or a maximum of three doses of cyclophosphamide (cumulative dose of 600 mg/m2) and the standard prephase treatment 5. With or without documented CNS involvement 6. Adequate liver function, including total serum bilirubin 40 mL/min 8. WHO performance status = 2 9. Signed written inform consent 10. Inclusion in GMALL registry Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
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 before start of study medication 4. Known systemic vasculitis (e.g., Wegener’s granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease) 5. Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV) 6. Major surgery within 2 years 9. Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 45%, or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure 10. Myocardial infarction < 6 months before entry on study 11. History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block 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 prolonging drug (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 any humanized monoclonal antibodies or any known hypersensitivity to the active substance or 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, following menarche and until becoming post-menopausal unless permanently sterile e.g. after hysterectomy or bilateral ovariectomy. Please refer to chapter 12.4 Contraceptive Requirements.) not using highly effective contraception or not agreeing to continue highly effective contraception for women at least 8 months and for men at least 5 months after the last dose of investigational product. 19. Participation in other studies involving investigational drug(s) (Phase I-IV) within 4 weeks before study inclusion 20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To evaluate the efficacy of an inotuzumab ozogamicin induction therapy, defined as the number of patients being alive in first remission one year after start of induction therapy. ;Secondary Objective: To evaluate the safety of an inotuzumab ozogamicin induction therapy. ;Primary end point(s): Event free survival (EFS) at 12-months follow-up. An event is any of the following: persisting bone marrow blasts (more than 5% leukemic blasts) after two cycles of inotuzumab ozogamicin, relapse, secondary malignancy or death.;Timepoint(s) of evaluation of this end point: After 12-months follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a. The rate of complete hematological remission after inotuzumab ozogamicin induction treatment b. The rate of patients being negative for minimal residual disease (defined by RQ-PCR for at least one leukemia-specific Ig/TCR gene rearrangement or leukemia specific genetic aberration with a sensitivity of at least 10-4) after induction treatment c. Relapse free survival after two years d. The proportion of patients with molecular relapse e. Overall survival after two years f. Death during induction g. Death in complete remission ;Timepoint(s) of evaluation of this end point: 24 months following initiation of Inotuzumab Ozogamicin | — |
Countries
Germany
Contacts
Public ContactMedizinische Klinik II
Goethe Universität
Outcome results
None listed