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A study is designed to assess if BL-8040 in combination with cytarabine (Ara-C) can help controlling the disease in patients with Acute Myeloid Leukemia (AML) that have relapsed or did not respond adequately to previous treatment. The safety of the study drug combination will also be studied.
Open-label, multicenter, Phase IIa, dose escalating study in subjects with relapsed/refractory AML, defined according to WHO criteria, including subjects who failed chemotherapy only and those who failed previous Autologous Stem Cell Transplantation (ASCT)/ Allogeneic Stem Cell Transplantation (AlloSCT), provided at least 6 months have passed from transplant.
Eligible subjects will receive subcutaneous (SC) injections of BL-8040 ("monotherapy period") over two days (one injection per day) followed by concurrent administration of BL-8040 with standard salvage chemotherapy ("combined period") over 5 days. During the "combined period," BL-8040 will be administered 4 hours prior to chemotherapy. The chemotherapy will consist of cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age), administered intravenously (IV) over 3 hours, for 5 days and will not be escalated.
The first part of the study (Part 1) will include escalating dose groups and be considered the 'escalation phase'. Six potential dose levels will be investigated starting at dose level 1. Patients will be accrued in a conventional 3+3 design. Applying this study design, the first cohort of 3 patients will be treated at dose level 1 and evaluated for dose escalation.
At the discretion of the Sponsor, additional subjects may be enrolled into a selected dose group to confirm safety and efficacy for selected dose. the portion of this study is considered expansion phase.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BL-8040 0.5mg/kg + Ara-C 1.5 or 3 g/m2/d per dose (based on age) | Experimental | Arm 1: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 0.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days. |
|
| BL-8040 0.75mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age) | Experimental | Arm 2: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 0.75 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days. |
|
| BL-8040 1.0mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age) | Experimental | Arm 3: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 1 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days. |
|
| BL-8040 1.25mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age) | Experimental | Arm 4: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 1.25 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ara-C | Drug | IV (intravenous administration) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability | Number of participants with Adverse event affecting the safety and tolerability of BL-8040 + Ara-C by dose level (overall, dose limiting events, related Adverse Events (AEs), Serious Adverse Events (SAEs), related SAEs, AE by severity and death) Toxicity grade was assessed according to version V4.03 of NCI-CTCAE | Participants were followed for the duration of the hospital stay and the follow-up period, an expected average of 6 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Response to Treatment by Dose | Response rate as assessed at final bone marrow evaluation based on Cheson et al 2003 criteria.
|
Not provided
Inclusion Criteria:
Adult men and women subjects aged 18 to 75, inclusive.
Confirmed diagnosis of relapsed/refractory AML (WHO criteria) Refractory subjects, up to second consecutive salvage . Relapsed subjects including first and second relapse.
AML relapse > 6 months since autologous or allogeneic stem cell transplantation, provided they are in first or second relapse and:
No active graft-versus-host disease (GVHD > grade 1). No treatment with high dose steroids for GVHD (up to 20 mg Prednisolone or equivalent, Appendix G). No treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus (blood levels of 0.5-0.6 µg/mL).
Clinical laboratory values should be as follows:
White Blood Cells (WBC) < 30,000/mL Blasts in Peripheral Blood (PB) ≤ 20,000. Treatment with Hydroxyurea is permitted up to 24 hrs prior to BL-8040 administration to achieve blast counts < 20,000 prior to enrollment. Creatinine < 1.3 mg/dL; if Creatinine is > 1 mg/dL the Creatinine clearance should be > 40 mL/min as calculated using the Cockcroft-Gault formula.
Women of childbearing potential and all men must agree to use an approved form of contraception (e.g. oral, transdermal patch, implanted contraceptives, intrauterine device, diaphragm, condom, abstinence or surgical sterility) prior to study entry and for the duration of study participation through 30 days after the last dose of BL-8040. Confirmation that female subjects are not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
Subject is able and willing to comply with the requirements of the protocol.
Subject is able to voluntarily provide written informed consent.
Exclusion Criteria:
Administration of conventional chemotherapy within 2 weeks of enrollment date. In the event that subjects have received chemotherapy > 2 weeks from the date of enrollment, they may be included provided they have recovered from the associated non-hematological toxicities to ≤ grade 1.
Life expectancy of ≤ 2 months.
Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product.
Use of investigational device or agents within 2 weeks of enrollment date.
Low Performance Status (ECOG > 2; Appendix E).
O2 saturation < 92% (on room air), evidence of Tumor Lysis Syndrome (TLS) > grade 2 (according to the Cairo-Bishop criteria (3)) or leukostasis (2).
Abnormal liver function tests:
Serum aspartate transaminase (AST/SGOT) or alanine transaminase ( Alanine Transaminase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT)) 2 x upper limit of normal (ULN).
Serum bilirubin. Total bilirubin > 2.0 mg/dL (34 µmol/L), conjugated bilirubin > 0.8 mg/dL.
Left ventricular ejection fraction < 40 %.
History of myocardial infarction or cerebrovascular accident within 6 months of enrollment date.
Presence of active, uncontrolled infection.
Known central nervous system disease (e.g., Alzheimer's disease).
Acute promyelocytic leukemia.
Exposure to high dose Ara-C within 6 months of enrollment.
Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to:
Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy A co-morbid condition which, in the view of the Investigators, renders the subject at high risk from treatment complications.
Female subjects who are pregnant or breastfeeding.
Prior clinically significant grade 3-4 non-hematological toxicity to high dose Ara-C or grade ≥ 2 of neurological toxicity.
Seropositive for HIV antibodies (HIV1 and HIV2), Hepatitis C antibody (Hep C Ab) or a Hepatitis B carrier (positive for Hepatitis B surface antigen [HBsAg]).
Unable to comply with study requirements in the opinion of the Investigator.
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| Name | Affiliation | Role |
|---|---|---|
| Arnon Aharon, MD | BioLineRx, Ltd. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Jacksonville | Florida | 32224 | United States | ||
| Johns Hopkins Sidney Kimmel Comprehensive Cancer Center |
Not provided
The study included 6 escalating dose groups
The decision to proceed to the next dose level was made by an independent Data Monitoring Committee (DMC) after review of the relevant safety data. At the discretion of the Sponsor, additional subjects could be enrolled into a selected dose group to confirm the safety, efficacy and pharmacokinetic (PK) profile for the selected dose.
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| ID | Title | Description |
|---|---|---|
| FG000 | Period 1: BL-8040 0.5 mg/kg + Ara-C | Participants were dosed with SC injections of 0.5 mg/kg BL-8040 over two days followed by concurrent administration of 0.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| FG001 | Period 2: BL-8040 0.75 mg/kg + Ara-C | Participants were dosed with SC injections of 0.75 mg/kg BL-8040 over two days followed by concurrent administration of 0.75 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| FG002 | Period 3: BL-8040 1.0 mg/kg + Ara-C | Participants were dosed with SC injections of 1.0 mg/kg BL-8040 over two days followed by concurrent administration of 1.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| FG003 | Period 4: BL-8040 1.25 mg/kg + Ara-C | Participants were dosed with SC injections of 1.25 mg/kg BL-8040 over two days followed by concurrent administration of 1.25 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| FG004 | Period 5 & Expansion Phase: BL-8040 1.5 mg/kg + Ara-C | Participants were dosed with SC injections of 1.5 mg/kg BL-8040 over two days followed by concurrent administration of 1.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| FG005 | Period 6: BL-8040 2.0 mg/kg + Ara-C | Participants were dosed with SC injections of 2.0 mg/kg BL-8040 over two days followed by concurrent administration of 2.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Period 1: 0.5 mg/kg BL-8040 + Ara-C | 0.5 mg/kg BL-8040 administration over two days followed by concurrent administration of 0.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| BG001 | Period 2: 0.75 mg/kg BL-8040 + Ara-C |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability | Number of participants with Adverse event affecting the safety and tolerability of BL-8040 + Ara-C by dose level (overall, dose limiting events, related Adverse Events (AEs), Serious Adverse Events (SAEs), related SAEs, AE by severity and death) Toxicity grade was assessed according to version V4.03 of NCI-CTCAE | All patients who received at least one dose of BL-8040 were included in the analysis (ITT) | Posted | Count of Participants | Participants | Participants were followed for the duration of the hospital stay and the follow-up period, an expected average of 6 weeks. |
|
Adverse Events (AEs) were assessed at all study visits throughout the study from completion of Informed Consent Form (ICF) until End of Study for each patient, which is approximately 3 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BL-8040 + Ara-C - All Patients | BL-8040 administration over two days followed by concurrent administration of BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| FEBRILE NEUTROPENIA | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| INJECTION SITE REACTION | General disorders | MedDRA (14.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| VP Clinical & Medical Affairs | BioLineRx Ltd. | +972-8-642-9100 | clinicaltrials@biolinerx.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 15, 2015 | Jun 24, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 14, 2016 | Jun 24, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D003561 | Cytarabine |
| C477728 | 4-fluorobenzoyl-TN-14003 |
| ID | Term |
|---|---|
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
The study (Part 1) will include escalating dose groups and be considered the 'escalation phase'. Five potential dose levels will be investigated starting at dose level 1. Patients will be accrued in a conventional 3+3 design. Applying this study design, the first cohort of 3 patients will be treated at dose level 1 and evaluated for dose escalation.
Dose escalation will be permitted until the Maximum Tolerated Dose (MTD) is established and protocol specific stopping rules for toxicity are met. If no MTD is reached, dose escalation will continue up to dose level 5 (1.5 mg/kg).
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| BL-8040 1.5mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age) | Experimental | Arm 5: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 1.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days. |
|
| BL-8040 2mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age) | Experimental | Arm 6: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 2 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days. |
|
|
| BL-8040 | Drug | SC (subcutaneous injection) |
|
| Final bone marrow evaluation - Between Day 20 and Day 44 |
| Apoptotic Effect | Change in leukemic cell apoptosis in peripheral blood and bone marrow | Final evaluation - between Day 20 and Day 44 |
| Assessment of the Pharmacokinetic Profile of BL-8040 - t1/2 (h) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 t1/2 (h): The time required for plasma concentration of a drug to decrease by 50% | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
| Assessment of the Pharmacokinetic Profile of BL-8040 - Tmax (h) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 tmax (h): The time to peak concentration | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
| Assessment of the Pharmacokinetic Profile of BL-8040 - Cmax (ng/mL) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 Cmax is the highest concentration of a drug in the blood | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
| Assessment of the Pharmacokinetic Profile of BL-8040 - AUC0-t (h*ng/mL) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 AUC0-t is the Area Under the Curve (AUC), definite integral of the concentration of a drug in blood as a function of time. | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
| Assessment of the Pharmacokinetic Profile of BL-8040 - AUC0-24 (h*ng/mL) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 AUC0-24 is the Area Under the Curve (AUC), definite integral of the concentration of a drug in blood from time zero to 24 hours post dose. | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
| Baltimore |
| Maryland |
| 21231 |
| United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10065 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Rambam Medical Center | Haifa | 31096 | Israel |
| Shaare Zedek Medical Center | Jerusalem | 91031 | Israel |
| Meir Medical Center | Kfar Saba | Israel |
| Chaim Sheba Medical Center | Ramat Gan | 52621 | Israel |
| Tel-Aviv Sourasky Medical Center | Tel Aviv | 64239 | Israel |
| Death |
|
| started conditioning regimen prior to hematopoietic stem cell transplant |
|
0.75 mg/kg BL-8040 administration over two days followed by concurrent administration of 0.75 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| BG002 | Period 3: 1.0 mg/kg BL-8040 + Ara-C | 1.0 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| BG003 | Period 4: 1.25 mg/kg BL-8040 + Ara-C | 1.25 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.25 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| BG004 | Period 5 & Expansion Phase: 1.5 mg/kg BL-8040 + Ara-C | 1.5 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| BG005 | Period 6: 2.0 mg/kg BL-8040 + Ara-C | 2.0 mg/kg BL-8040 administration over two days followed by concurrent administration of 2.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Period 1: BL-8040 0.5 mg/kg + Ara-C | 0.5 mg/kg BL-8040 administration over two days followed by concurrent administration of 0.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| OG002 | Period 2: BL-8040 0.75 mg/kg + Ara-C | 0.75 mg/kg BL-8040 administration over two days followed by concurrent administration of 0.75 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days |
| OG003 | Period 3: BL-8040 1.0 mg/kg + Ara-C | 1.0 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| OG004 | Period 4: BL-8040 1.25 mg/kg + Ara-C | 1.25 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.25 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| OG005 | Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C | 1.5 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
| OG006 | Period 6: BL-8040 2.0 mg/kg + Ara-C | 2.0 mg/kg BL-8040 administration over two days followed by concurrent administration of 2.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days. |
|
|
| Secondary | Response to Treatment by Dose | Response rate as assessed at final bone marrow evaluation based on Cheson et al 2003 criteria.
| Posted | Number | participants | Final bone marrow evaluation - Between Day 20 and Day 44 |
|
|
|
| Secondary | Apoptotic Effect | Change in leukemic cell apoptosis in peripheral blood and bone marrow | Data were not collected | Posted | Final evaluation - between Day 20 and Day 44 |
|
|
| Secondary | Assessment of the Pharmacokinetic Profile of BL-8040 - t1/2 (h) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 t1/2 (h): The time required for plasma concentration of a drug to decrease by 50% | PK Population | Posted | Mean | Standard Deviation | hours | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
|
|
|
| Secondary | Assessment of the Pharmacokinetic Profile of BL-8040 - Tmax (h) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 tmax (h): The time to peak concentration | PK Population | Posted | Mean | Standard Deviation | hours | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
|
|
|
| Secondary | Assessment of the Pharmacokinetic Profile of BL-8040 - Cmax (ng/mL) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 Cmax is the highest concentration of a drug in the blood | PK Population | Posted | Mean | Standard Deviation | ng/mL | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
|
|
|
| Secondary | Assessment of the Pharmacokinetic Profile of BL-8040 - AUC0-t (h*ng/mL) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 AUC0-t is the Area Under the Curve (AUC), definite integral of the concentration of a drug in blood as a function of time. | PK Population | Posted | Mean | Standard Deviation | h*ng/mL | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
|
|
|
| Secondary | Assessment of the Pharmacokinetic Profile of BL-8040 - AUC0-24 (h*ng/mL) | Pharmacokinetics (PK) of BL-8040 after daily subcutaneous (SC) dosing for 2 days alone, followed by 5 days of combined administration of BL-8040 + Ara-C by dose level. Standard Deviation is reported for N ≥ 3 AUC0-24 is the Area Under the Curve (AUC), definite integral of the concentration of a drug in blood from time zero to 24 hours post dose. | PK Population | Posted | Mean | Standard Deviation | h*ng/mL | Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1. |
|
|
|
| 2 |
| 42 |
| 21 |
| 42 |
| 41 |
| 42 |
| EG001 | Period 1: BL-8040 0.5 mg/kg + Ara-C | 0.5 mg/kg BL-8040 administration over two days followed by concurrent administration of 0.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days | 0 | 3 | 1 | 3 | 3 | 3 |
| EG002 | Period 2: BL-8040 0.75 mg/kg + Ara-C | 0.75 mg/kg BL-8040 administration over two days followed by concurrent administration of 0.75 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days | 0 | 3 | 3 | 3 | 3 | 3 |
| EG003 | Period 3: BL-8040 1.0 mg/kg + Ara-C | 1.0 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days | 1 | 6 | 3 | 6 | 6 | 6 |
| EG004 | Period 4: BL-8040 1.25 mg/kg + Ara-C | 1.25 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.25 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days | 1 | 4 | 1 | 4 | 4 | 4 |
| EG005 | Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C | 1.5 mg/kg BL-8040 administration over two days followed by concurrent administration of 1.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days | 0 | 23 | 10 | 23 | 22 | 23 |
| EG006 | Open Label 2.0 mg/kg Period 6: BL-8040 2.0mg/kg + Ara-C | 2.0 mg/kg BL-8040 administration over two days followed by concurrent administration of 2.0 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) over 5 days | 0 | 3 | 3 | 3 | 3 | 3 |
| ATRIAL FIBRILLATION | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| CHEST PAIN | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| HYPERSENSITIVITY | Immune system disorders | MedDRA (14.0) | Systematic Assessment | HYPERSENSITIVITY |
|
| ESCHERICHIA BACTERAEMIA | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| FALL | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| ATAXIA | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| PRESYNCOPE | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
| ACUTE FEBRILE NEUTROPHILIC DERMATOSIS | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| HYPOTENSION | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Alpha haemolytic streptococcal infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Lung Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (14.0) | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA (14.0) | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA (14.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (14.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (14.0) | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
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| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Leukoplakia oral | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Lip Ulceration | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site bruising | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (14.0) | Systematic Assessment |
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| Injection site induration | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site joint pain | General disorders | MedDRA (14.0) | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site rash | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site urticaria | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Injection site warmth | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA (14.0) | Systematic Assessment |
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| Generalised oedema | General disorders | MedDRA (14.0) | Systematic Assessment |
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| Oedema | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hyperbilirubinemia | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (14.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Stomatococcal infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Enterococcal infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Catheter site infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Pseudomonal bacteraemia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Alpha haemolytic streptococcal infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Tongue injury | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Enterobacter test positive | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Blood phosphorus increased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (14.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hyperglicaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Fluid retention | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (14.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (14.0) | Systematic Assessment |
|
| Acute Kidney Injury | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Generalised erythema | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Thrombophlebitis superficial | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Hypovolaemic shock | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Catheter site haematoma | General disorders | MedDRA (14.0) | Systematic Assessment |
|
Not provided
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006571 |
| Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| Complete response with incomplete recovery (CRi) |
|
| Partial Response (PR) |
|
| Overall Response (CR+CRi+PR) |
|
| Complete Response (CR and CRi) |
|