GNR-084 Safety and Pharmacological Characteristics in Refractory or Relapse B-cell Precursor ALL

Inclusion Criteria:

1. Voluntarily signed informed consent form to participate in the study;
2. Men and women between aged 18 to 45 inclusive;
3. Patients with incurable morphologically / immunophenotypically confirmed refractory/relapse of B-cell precursors CD19-positive acute lymphoblastic leukemia from (Ph "-"or Ph "+").
4. Two or more previous lines of anti-leucosis therapy.
5. 5-50% of bone marrow blast cells at screening;
6. Functional status on the scale of the Eastern Cooperative Oncology Group (ECOG) 0-2points at the screening;
7. Life expectancy ≥ 60 days;

Exclusion Criteria:

1. Hematopoietic stem cells transplantation within 12 weeks prior to study inclusion;
2. Active and widespread chronic graft versus host (GVHD) reaction (grade II-IV),including taking immunosuppressants for the prevention and treatment of GVHD within 2weeks prior the GNR-084 infusion;
3. Investigator and / or sponsor has doubts that patient will complete the study due torapid disease progression;
4. Chemotherapeutic agent using within 14 days prior the first GNR-084 infusion; Exceptions:

• Emergency leukapheresis;
• Emergency hydroxyurea using due to hyperleukocytosis for ≤ 7 days;
• Other supportive care, including antibiotics, at Investigator's discretion

5. Biochemical blood test:

• The level of total bilirubin> 1.5 upper limit of norm;
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)> 3 upperlimit of norm;
• Glomerular filtration rate (GFR) level ≤30 (СKD-EPI)

6. Medical history of blinatumomab and other bispecific antibodies using;
7. Persistent toxicity event of 3rd and 4th severity degrees (CTCAE ver 5.0) due toprevious treatment;
8. HIV-positive status and / or detection of any hepatitis B and / or hepatitis C bloodmarkers;
9. Severe cardiovascular diseases: uncontrolled arterial hypertension, New York HeartAssociation (NYHA) functional class III or IV chronic heart failure, unstable anginapectoris, stroke, myocardial infarction, transient ischemic attack, coronary arterybypass grafting and coronary revascularization within last 12 months, or signs ofpericardial effusion;
10. Individual sensitivity to:

• GNR-084 components / excipients;
• human or humanized investigational drug antibodies;

11. Major surgical interventions, accompanied by hospitalization and anesthesiaapplication within 30 days before the patient is included in the study (biopsy is nota significant surgical intervention);
12. Any other malignant neoplasm presence at the present time or within 5 years prior toinclusion in the study;
13. Known suspected Central Nervous System (CNS) lesion by any genesis now or in medicalhistory, including, but not limited to: neuroleukemia, epilepsy, ischemic orhemorrhagic stroke, severe traumatic brain injury, dementia, Parkinson's disease,organic brain damage, cerebellar disorders, psychosis;
14. Extramedullary lesion of any localization;
15. Other clinical trials participation within 30 days before screening;
16. Mental, physical and other reasons hindering patient to adequately assess theirbehavior and correctly comply with the conditions of the research protocol;
17. Pregnancy and / or lactation;
18. Male and female patients refusal to use adequate methods of contraception throughoutthe study;
19. Drug addiction;
20. Alcohol addiction.