Blinatumomab Followed by High-dose Chemotherapy for Ph-negative Acute Lymphoblastic Leukemia (ALL)

Prior treatment

• Persisting ALL in the CNS at the end of run-in period; patients with initial cerebrospinal fluid (CSF) infiltration arriving into CSF negativity after up to 4 intrathecal applications of chemotherapy within the first 10 days of therapy are allowed for the study;
• Vaccination with a live virus vaccine within 4 weeks prior to the study enrolment;
• Female patients who are pregnant or breast feeding or patients of childbearing potential not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of study drug;
• Any of concurrent severe and/or uncontrolled medical condition, which could, in the opinion of the investigator, compromise participation in the study;
• Concurrent participation in another clinical study with an investigational medical product.

Other illness

• History of malignancy other than ALL within 5 years prior to start of protocol-required therapy, except for:
  • Malignancy treated with curative intent and with no known active disease present for 5 years before enrollment and felt to be at low risk for recurrence by the treating physician;
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of 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.
• History or presence of central nervous system (CNS) pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis;
• Current autoimmune disease or history of autoimmune disease with potential CNS involvement;
• Active known hepatitis B virus (HBV) or hepatitis C virus (HCV) or positive HIV serology;
• Hypersensitivity to any active substance contained in blinatumomab, including polysorbate 80;

Other

• Male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a double barrier method of contraception, one of which includes a condom, during the study;

• Age 18-65 years;
• Lymphoblasts positive for CD19;
• Eligible to intensive chemotherapy, due to general health status;
• With newly diagnosed B-precursor-ALL;
• Without BCR-ABL fusion by FISH analysis and/or RT-PCR;
• Blasts expressing the CD19 antigen by flow cytometry;
• Previously untreated;
• ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2;
• Diagnostic sample of bone marrow (or peripheral blood with \>50% of blasts) available for central MRD assessment
• Written informed consent obtained prior to any screening procedures.