Phase IIa Study Evaluating Safety and Efficacy of BL-8040 in Relapsed/Refractory AML Patients

A Phase IIa, Multicenter, Open-Label Study Designed to Evaluate the Safety and Efficacy of Escalating Doses of BL-8040 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01838395

Enrollment

Registered

2013-04-24

Start date

2013-04-30

Completion date

2023-07-20

Last updated

2024-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Myeloid Leukemia

Keywords

AML, Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

Brief summary

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.

Detailed description

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.

Interventions

DRUGAra-C

IV (intravenous administration)

DRUGBL-8040

SC (subcutaneous injection)

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

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).

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

1. Adult men and women subjects aged 18 to 75, inclusive. 2. Confirmed diagnosis of relapsed/refractory AML (WHO criteria) Refractory subjects, up to second consecutive salvage . Relapsed subjects including first and second relapse. 3. 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). 4. 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. 5. 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. 6. Subject is able and willing to comply with the requirements of the protocol. 7. Subject is able to voluntarily provide written informed consent.

Exclusion criteria

1. 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. 2. Life expectancy of ≤ 2 months. 3. Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product. 4. Use of investigational device or agents within 2 weeks of enrollment date. 5. Low Performance Status (ECOG \> 2; Appendix E). 6. O2 saturation \< 92% (on room air), evidence of Tumor Lysis Syndrome (TLS) \> grade 2 (according to the Cairo-Bishop criteria (3)) or leukostasis (2). 7. 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. 8. Left ventricular ejection fraction \< 40 %. 9. History of myocardial infarction or cerebrovascular accident within 6 months of enrollment date. 10. Presence of active, uncontrolled infection. 11. Known central nervous system disease (e.g., Alzheimer's disease). 12. Acute promyelocytic leukemia. 13. Exposure to high dose Ara-C within 6 months of enrollment. 14. 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. 15. Female subjects who are pregnant or breastfeeding. 16. Prior clinically significant grade 3-4 non-hematological toxicity to high dose Ara-C or grade ≥ 2 of neurological toxicity. 17. Seropositive for HIV antibodies (HIV1 and HIV2), Hepatitis C antibody (Hep C Ab) or a Hepatitis B carrier (positive for Hepatitis B surface antigen \[HBsAg\]). 18. Unable to comply with study requirements in the opinion of the Investigator.

Design outcomes

Primary

Measure	Time frame	Description
Safety and Tolerability	Participants were followed for the duration of the hospital stay and the follow-up period, an expected average of 6 weeks.	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

Secondary

Measure	Time frame	Description
Apoptotic Effect	Final evaluation - between Day 20 and Day 44	Change in leukemic cell apoptosis in peripheral blood and bone marrow
Assessment of the Pharmacokinetic Profile of BL-8040 - t1/2 (h)	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.	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%
Assessment of the Pharmacokinetic Profile of BL-8040 - Tmax (h)	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.	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
Response to Treatment by Dose	Final bone marrow evaluation - Between Day 20 and Day 44	Response rate as assessed at final bone marrow evaluation based on Cheson et al 2003 criteria. * CR defined as bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0 x 10\^9/L (1000/μL); platelet count \>100 x 10\^9/L (100,000/μL); independent of red cell transfusions * CRi defined as all CR criteria except for residual neutropenia (\<1.0 x 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 x 10\^9/L \[100,000/μL\]) * Partial Response (PR) defined as all hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%
Assessment of the Pharmacokinetic Profile of BL-8040 - AUC0-t (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.	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.
Assessment of the Pharmacokinetic Profile of BL-8040 - AUC0-24 (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.	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.
Assessment of the Pharmacokinetic Profile of BL-8040 - Cmax (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.	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

Countries

Israel, United States

Participant flow

Recruitment details

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.

Participants by arm

Arm	Count
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.	3
Period 2: 0.75 mg/kg BL-8040 + 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.	3
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.	6
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.	4
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.	23
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.	3
Total	42

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG004
Overall Study	Death	0	1	0
Overall Study	started conditioning regimen prior to hematopoietic stem cell transplant	1	0	0
Overall Study	Withdrawal by Subject	0	0	1

Baseline characteristics

Characteristic	Period 1: 0.5 mg/kg BL-8040 + Ara-C	Total	Period 6: 2.0 mg/kg BL-8040 + Ara-C	Period 5 & Expansion Phase: 1.5 mg/kg BL-8040 + Ara-C	Period 4: 1.25 mg/kg BL-8040 + Ara-C	Period 3: 1.0 mg/kg BL-8040 + Ara-C	Period 2: 0.75 mg/kg BL-8040 + Ara-C
Age, Continuous	61.7 years STANDARD_DEVIATION 10.5	60.2 years STANDARD_DEVIATION 9.9	52.3 years STANDARD_DEVIATION 20	61.3 years STANDARD_DEVIATION 8.8	62.3 years STANDARD_DEVIATION 10.2	56.8 years STANDARD_DEVIATION 10.9	62.0 years STANDARD_DEVIATION 6.1
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	38 Participants	2 Participants	20 Participants	4 Participants	6 Participants	3 Participants
Sex: Female, Male Female	2 Participants	19 Participants	2 Participants	10 Participants	2 Participants	2 Participants	1 Participants
Sex: Female, Male Male	1 Participants	23 Participants	1 Participants	13 Participants	2 Participants	4 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	2 / 42	0 / 3	0 / 3	1 / 6	1 / 4	0 / 23	0 / 3
other Total, other adverse events	41 / 42	3 / 3	3 / 3	6 / 6	4 / 4	22 / 23	3 / 3
serious Total, serious adverse events	21 / 42	1 / 3	3 / 3	3 / 6	1 / 4	10 / 23	3 / 3

Outcome results

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

Time frame: Participants were followed for the duration of the hospital stay and the follow-up period, an expected average of 6 weeks.

Population: All patients who received at least one dose of BL-8040 were included in the analysis (ITT)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
BL-8040 + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE	21 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event : Death	2 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE also drug-related (Definite/Probable)	1 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event: Subjects with any dose-limiting event (per patient)	3 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event: Subjects with serious AE also drug-related (Definite/Probable/Possible)	3 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event: Subjects with any adverse event (per patient)	42 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event : Subjects with mild and/or moderate AE	41 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable)	35 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event : Subjects with severe or life-threatening AE	33 Participants
BL-8040 + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable/Possible)	40 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any dose-limiting event (per patient)	0 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable/Possible)	2 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable)	1 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE	1 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with serious AE also drug-related (Definite/Probable/Possible)	0 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE also drug-related (Definite/Probable)	0 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any adverse event (per patient)	3 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with mild and/or moderate AE	3 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with severe or life-threatening AE	2 Participants
Period 1: BL-8040 0.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Death	0 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with mild and/or moderate AE	3 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any dose-limiting event (per patient)	0 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with severe or life-threatening AE	3 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Death	0 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable/Possible)	3 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with serious AE also drug-related (Definite/Probable/Possible)	0 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE also drug-related (Definite/Probable)	0 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE	3 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable)	3 Participants
Period 2: BL-8040 0.75 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any adverse event (per patient)	3 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with mild and/or moderate AE	6 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with severe or life-threatening AE	4 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Death	1 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any dose-limiting event (per patient)	0 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable)	4 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable/Possible)	5 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE	3 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE also drug-related (Definite/Probable)	0 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any adverse event (per patient)	6 Participants
Period 3: BL-8040 1.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with serious AE also drug-related (Definite/Probable/Possible)	0 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any adverse event (per patient)	4 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE also drug-related (Definite/Probable)	0 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with serious AE also drug-related (Definite/Probable/Possible)	0 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable)	4 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any dose-limiting event (per patient)	0 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Death	1 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with severe or life-threatening AE	2 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with mild and/or moderate AE	4 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE	1 Participants
Period 4: BL-8040 1.25 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable/Possible)	4 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE	10 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any adverse event (per patient)	23 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any dose-limiting event (per patient)	3 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable)	20 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable/Possible)	23 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE also drug-related (Definite/Probable)	1 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with serious AE also drug-related (Definite/Probable/Possible)	3 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with severe or life-threatening AE	19 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with mild and/or moderate AE	22 Participants
Period 5 & Expansion: BL-8040 1.5 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Death	0 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE also drug-related (Definite/Probable)	0 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any serious AE	3 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any dose-limiting event (per patient)	0 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with mild and/or moderate AE	3 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Death	0 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable/Possible)	3 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any drug-related AE (Definite/Probable)	3 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with any adverse event (per patient)	3 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event : Subjects with severe or life-threatening AE	3 Participants
Period 6: BL-8040 2.0 mg/kg + Ara-C	Safety and Tolerability	Adverse event: Subjects with serious AE also drug-related (Definite/Probable/Possible)	0 Participants

Secondary

Apoptotic Effect

Change in leukemic cell apoptosis in peripheral blood and bone marrow

Time frame: Final evaluation - between Day 20 and Day 44

Population: Data were not collected

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.