Acute Myeloid Leukemia
Conditions
Interventions
Product Name: BL-8040
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Not available
CAS Number: 664334-36-5
4F-benzoyl-TN14003
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 36.5-
Product Name
Sponsors
BioLineRx, Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult men and women subjects aged = 60 years. 2. Confirmed diagnosis of AML (according to WHO criteria. See Appendix C) 3. Subjects with newly diagnosed AML who have achieved Complete Remission (CR or CRi), after up to two cycles of induction chemotherapy. 4. Subjects with intermediate I, II or adverse risk factors according to the ENL guidelines 2017. 5. Induction therapy must have included cytarabine and may also have included an anthracycline or mitoxantrone. 6. CR (or CRi) must be confirmed by bone marrow aspirate up to 21 days prior to enrollment. 7. Subjects who have received 1-4 cycles of cytarabine-based consolidation therapy unless they have been deemed intolerant of consolidation therapy. 8. Subjects who prior to screening are MRD positive according to local laboratory or with an unknown MRD status; are to be confirmed or tested, respectively, for MRD by central laboratory prior to enrollment. 9. Subjects who are diagnosed with AML within one year prior to study enrollment. 10. Subjects should have received the last dose of the last induction or consolidation treatment within 2 months prior to study enrollment 11. Subjects who are not planned for allogeneic stem cell transplantation. 12. Female subjects must be post-menopausal or of non-childbearing potential defined as absence of menses for > 1 year or those who have had a bilateral tubal ligation or hysterectomy. 13. Male subjects with partners of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through at least 5 months after the last dose of study therapy. Examples of adequate methods are: for males-condom with or without spermicide, sexual abstinence or surgical sterility (vasectomy) or for female partners with childbearing potential –oral, transdermal patch, implanted contraceptives, intrauterine device, diaphragm. 14. Subject is able and willing to comply with the requirements of the protocol. 15. Subject is able to voluntarily provide written informed consent prior to the initiation of any screening or study-related procedures 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 30
Exclusion criteria
Exclusion criteria: 1. Subjects diagnosed with acute promyelocytic leukemia. 2. Subjects with extramedullary AML, including CNS involvement. 3. Subjects who have achieved CR or CRi following treatment for relapsed or refractory AML after 2 inductions. 4. Subjects in CR1 following autologous or allogeneic stem cell transplantation. 5. Subjects who are candidates for allogenic stem cell transplantation and have a suitable donor. 6. Subjects who have received treatment with hypomethylating agents for their AML, e.g., azacitidine and decitabine, etc. 7. Life expectancy of = 6 months. 8. Clinically significant abnormal laboratory safety test values. 9. Low Performance Status (ECOG > 2) 10. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha [anti- TNF-a] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study. 11. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2) within 4 weeks or five halflives of the drug (whichever is longer) prior to initiation of study treatment. 12. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment with Atezolizumab or within 5 months after the last dose of Atezolizumab 13. Prior treatment with immune checkpoint blockade therapies (anti-CTLA-4, anti-PD-1, or anti-PD-L1) or immune agonists (anti-CD137, anti-CD40, anti-OX40). 14. Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product. 15. Use of investigational device or drug within 2 weeks or five halflives, whichever is longer, prior to the enrolment date. 16. Past or current history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune myocarditis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis. 17. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 18. Presence of active, uncontrolled infection or any serious infection including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia requiring hospitalization. 19. Treatment with IV antibiotics within 14 days prior to baseline. Subjects on prophylactic antibiotics, antifungals and antivirals, e.g., to prevent a urinary tract infection, chronic obstructive pulmonary disease exacerbation or due to prolonged neutropenia in the absence of documented infection will be considered eligible. 20. Subjects wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that the combination of BL-8040 and Atezolizumab prolongs the relapse free survival (RFS) time as compared to historical data.; Secondary Objective: To demonstrate that the combination of BL-8040 and Atezolizumab reduces the Minimal Residual Disease (MRD) as compared to baseline. • To demonstrate that the combination of BL-8040 and Atezolizumab prolongs the Overall Survival (OS) time as compared to historical data. • To demonstrate that the combination of BL-8040 and Atezolizumab prolongs the Event Free Survival (EFS) time as compared to historical data. • To demonstrate that the combination of BL-8040 and Atezolizumab prolongs the time to first relapse as compared to historical data. ;Primary end point(s): Time from CR to occurrence of earlier relapse or death from any cause (RFS).;Timepoint(s) of evaluation of this end point: Depending upon occurence. Study duration will not exceed 4.5 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • Change from baseline to Cycles 3, 9, 17 and 34 in MRD status measured using quantitative, multi-color, flow cytometry. • Time from 1st study drug administration to death from any cause (OS). • Event Free Survival (EFS) measured as the earlier from 1st study drug administration to the date of primary refractory disease, or relapse from CR, or death from any cause from 1st study drug administration. • Time from CR to first relapse (TTR). ;Timepoint(s) of evaluation of this end point: Depending upon occurence. Study duration will not exceed 4.5 years. | — |
Countries
Czech Republic, Hungary, Israel, Poland, Slovakia, Spain, United States
Contacts
Public ContactClinical Team Executive Assistant
BioLineRx, Ltd.
Outcome results
None listed