A Phase III, Randomized, Placebo-Controlled, Multi-Centre Study Evaluating the Safety, Tolerability and Efficacy of Combination Treatment of BL-8040 and G-CSF as Compared to Placebo and G-CSF for the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Subjects With Multiple Myeloma - The GENESIS Study
Phase: PHASE3
Conditions: Multiple Myeloma
Sponsor: BioLineRx, Ltd.

Official Title: A Phase III, Randomized, Double-Blinded, Placebo-Controlled, Multi-
Centre Study Evaluating the Safety, Tolerability and Efficacy of Combination 
Treatment of BL-8040 and G-CSF as compared to Placebo and G-CSF for the 
Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Subjects 
with Multiple Myeloma – The GENESIS Study 
NCT Number: NCT03246529 
Document Date: 21 April 2020 

 
 
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Confidentiality Statement: 
This protocol is a confidential communication document of BioLineRx, Ltd. The recipient 
of this document agrees not to disclose the information contained herein to others without 
prior written authorization of BioLineRx, Ltd. except that this document may be disclosed 
to appropriate Institutional Review Boards/Independent Ethics Committees or duly 
authorized representatives of Regulatory authorities, under the condition that they maintain 
confidentiality. 

 
 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ........................................................................................................ 4 
LIST OF TABLES ................................................................................................................... 7 
TABLE OF FIGURES ............................................................................................................. 7 
LIST OF APPENDICES ......................................................................................................... 8 
PROTOCOL SYNOPSIS ........................................................................................................ 9 
GLOSSARY............................................................................................................................ 39 
1. 
INTRODUCTION...................................................................................................... 42 
1.1 
THERAPEUTIC INDICATION ......................................................................................... 42 
1.2 
INVESTIGATIONAL THERAPY ...................................................................................... 42 
1.2.1 BL-8040 ....................................................................................................................... 42 
1.2.2 G-CSF (Filgrastim) ...................................................................................................... 44 
1.2.3 Transplantation ............................................................................................................ 45 
1.3 
STUDY RATIONALE ...................................................................................................... 46 
2. 
STUDY OBJECTIVES AND ENDPOINTS ............................................................ 47 
2.1 
STUDY OBJECTIVES ..................................................................................................... 47 
2.1.1 Primary Objective ........................................................................................................ 47 
2.1.2 Secondary Objectives................................................................................................... 47 
2.1.3 Exploratory Objectives ................................................................................................ 47 
2.1.4 Safety and Tolerability Objectives ............................................................................... 48 
2.1.5 Pharmacokinetic Endpoint ........................................................................................... 48 
2.1.6 Pharmacoeconomic Endpoints ..................................................................................... 48 
2.2 
STUDY ENDPOINTS/OUTCOMES .................................................................................. 48 
2.2.1 Efficacy Endpoints ....................................................................................................... 48 
2.2.2 Exploratory Biomarkers ............................................................................................... 49 
2.2.3 Safety and Tolerability Outcomes ............................................................................... 49 
2.2.4 Pharmacokinetic Endpoint ........................................................................................... 49 
2.2.5 Pharmacoeconomic Endpoints ..................................................................................... 49 
3. 
STUDY DESIGN ........................................................................................................ 49 
3.1 
PART 1 .......................................................................................................................... 49 
3.2 
PART 2 .......................................................................................................................... 50 
3.3 
BOTH PARTS ................................................................................................................ 50 
4. 
STUDY POPULATION ............................................................................................ 52 
4.1 
NUMBER OF SUBJECTS ................................................................................................. 52 
4.2 
INCLUSION CRITERIA .................................................................................................. 52 
4.3 
EXCLUSION CRITERIA ................................................................................................. 54 
4.4 
SUBJECT IDENTIFICATION ........................................................................................... 56 
4.5 
SCREENING FAILURES ................................................................................................. 56 
4.6 
REMOVAL, EARLY WITHDRAWAL OF SUBJECTS FROM THERAPY OR ASSESSMENT 56 
4.7 
HANDLING OF WITHDRAWALS ................................................................................... 56 
4.8 
SPONSOR'S TERMINATION OF STUDY ......................................................................... 57 
5. 
STUDY PROCEDURES AND ASSESSMENTS .................................................... 57 

 
 
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5.1 
SCREENING PERIOD (FROM THE TIME OF INFORMED CONSENT FORM (ICF) 
SIGNATURE UNTIL DAY 0 (BASELINE VISIT)) ............................................................. 57 
5.2 
TREATMENT PERIOD ................................................................................................... 59 
5.2.1 Baseline Visit (Visit Day 0) ......................................................................................... 59 
5.2.2 Randomization (Part 2 only) ........................................................................................ 59 
5.2.3 Schedule of Treatment Period (Day 1 to Day 8) .......................................................... 60 
5.2.4 Apheresis procedure..................................................................................................... 67 
5.2.5 Rescue Procedure ......................................................................................................... 67 
5.2.6 Post Treatment Period .................................................................................................. 67 
5.2.7 Visit 11-13: Graft Durability and Core Study Termination Visit ................................ 69 
5.2.8 Long Term Disease Assessment Follow-Up Post Transplantation.............................. 72 
5.3 
SAFETY ASSESSMENTS ................................................................................................ 72 
5.3.1 Adverse Events (AEs) .................................................................................................. 72 
5.3.2 Concomitant Medications ............................................................................................ 73 
5.3.3 Vital Signs .................................................................................................................... 73 
5.3.4 Electrocardiogram ........................................................................................................ 74 
5.3.5 During Parts 1 and 2 .................................................................................................... 75 
5.3.6 Laboratory Assessments .............................................................................................. 76 
5.3.7 Assessment of Anti-Drug Antibodies (ADA), Complement Activation and Mast Cell 
Activation ..................................................................................................................... 78 
5.4 
EFFICACY ASSESSMENTS............................................................................................. 78 
5.4.1 CD34+ Cell Enumeration in the Apheresis Product .................................................... 78 
5.4.2 CD34+ Cell Enumeration in Peripheral Blood (PB) ................................................... 78 
5.4.3 Assessment of Engraftment by CBC ........................................................................... 79 
5.5 
DISEASE STATUS ASSESSMENT BY BONE MARROW BIOPSIES ................................... 79 
5.6 
PK ASSESSMENTS ........................................................................................................ 79 
5.7 
BLOOD SAMPLING AND PROCESSING .......................................................................... 79 
5.8 
PHARMACOECONOMIC ASSESSMENTS ........................................................................ 80 
6. 
INVESTIGATIONAL PRODUCT........................................................................... 80 
6.1 
IDENTITY OF INVESTIGATIONAL PRODUCT ................................................................ 80 
6.2 
STUDY DRUG ADMINISTRATION AND DOSAGE ........................................................... 80 
6.2.1 BL-8040 or Placebo ..................................................................................................... 80 
6.2.2 G-CSF .......................................................................................................................... 82 
6.3 
MANUFACTURING OF STUDY MEDICATION ................................................................ 83 
6.3.1 BL-8040 ....................................................................................................................... 83 
6.3.2 G-CSF .......................................................................................................................... 83 
6.4 
PACKAGING AND LABELING OF STUDY MEDICATION................................................ 83 
6.5 
DISTRIBUTION AND SHIPMENT OF STUDY MEDICATION ............................................ 83 
6.6 
STORAGE, DISPENSING AND RETURN OF THE INVESTIGATIONAL MEDICINAL 
PRODUCT ..................................................................................................................... 84 
6.6.1 BL-8040 or Placebo ..................................................................................................... 84 
6.6.2 G-CSF (Filgrastim) ...................................................................................................... 84 
6.7 
ACCOUNTABILITY AND COMPLIANCE OF INVESTIGATIONAL MEDICINAL PRODUCT
...................................................................................................................................... 84 

 
 
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6.8 
CONCOMITANT THERAPY ........................................................................................... 85 
6.8.1 Acceptable Concomitant Medications ......................................................................... 85 
6.8.2 Prohibited Concomitant Medications .......................................................................... 86 
7. 
SAFETY AND PHARMACOVIGILANCE ............................................................ 87 
7.1 
ADVERSE EVENT (AE)................................................................................................. 87 
7.2 
SERIOUS ADVERSE EVENTS (SAES) ............................................................................ 89 
7.3 
DEFINITION OF AN UNEXPECTED ADVERSE EVENT ................................................... 90 
7.4 
EXCEPTIONS IN THE REPORTING OF SAE .................................................................. 90 
7.5 
NOTIFICATION OF SERIOUS ADVERSE EVENT (SAE) ................................................. 91 
7.6 
TIMEFRAME FOR REPORTING REQUIRED EVENTS .................................................... 92 
8. 
STATISTICAL METHODOLOGY......................................................................... 93 
8.1 
GENERAL ..................................................................................................................... 93 
8.2 
RANDOMIZATION ......................................................................................................... 93 
8.3 
INTERIM ANALYSIS, TYPE-I ERROR AND MULTIPLICITY ADJUSTMENT ................... 93 
8.4 
SAMPLE SIZE JUSTIFICATION ..................................................................................... 94 
8.4.1 Sample Size Justification for Part 1 (Open labeled period for ascertaining the BL-
8040 dose optimization) ............................................................................................... 94 
8.4.2 Sample Size Justification for Part 2 (Randomized, Placebo-Controlled Part) ............. 94 
8.5 
DATA ANALYSES SETS ................................................................................................. 95 
8.6 
SEQUENCE OF PLANNED ANALYSES ............................................................................ 95 
8.7 
INTERIM ANALYSES ..................................................................................................... 97 
8.8 
EFFICACY ENDPOINTS AND ANALYSES ....................................................................... 98 
8.8.1 Primary Efficacy Endpoint and Principal Statistical Analysis .................................... 98 
8.8.2 Secondary Efficacy Endpoints and Statistical Analysis .............................................. 99 
8.8.3 Additional Secondary Efficacy Endpoints and Between Study Groups Descriptive 
Comparability Assessment......................................................................................... 100 
8.8.4 Exploratory Endpoints ............................................................................................... 101 
8.9 
SAFETY AND TOLERABILITY ANALYSES ................................................................... 102 
8.9.1 Adverse Events .......................................................................................................... 102 
8.9.2 Safety Laboratory Data .............................................................................................. 102 
8.9.3 Vital Signs .................................................................................................................. 103 
8.9.4 Physical Examinations ............................................................................................... 103 
8.9.5 12-Lead ECG ............................................................................................................. 103 
8.9.6 Tolerability Assessment ............................................................................................. 104 
8.10 
PHARMACOKINETIC ASSESSMENTS .......................................................................... 104 
8.11 
MORE DETAILED STATISTICAL ANALYSIS PLAN (SAP) .......................................... 104 
8.12 
STATISTICAL SOFTWARE .......................................................................................... 104 
9. 
ETHICS .................................................................................................................... 105 
9.1 
INSTITUTIONAL REVIEW BOARD (IRB) OR INDEPENDENT ETHICS COMMITTEE 
(IEC) .......................................................................................................................... 105 
9.2 
ETHICAL CONDUCT OF THE STUDY ........................................................................... 105 
9.3 
SUBJECT INFORMATION AND CONSENT .................................................................... 105 
9.4 
SUBJECT INSURANCE ................................................................................................. 106 
9.5 
INFORMING THE GENERAL PRACTITIONER.............................................................. 106 

 
 
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9.6 
PERSONAL DATA PROTECTION ................................................................................. 106 
9.7 
DATA AND SAFETY MONITORING ............................................................................. 106 
9.8 
PROTOCOL EXCEPTIONS AND DEVIATIONS .............................................................. 106 
9.9 
PROTOCOL AMENDMENTS ........................................................................................ 106 
10. 
QUALITY CONTROL AND QUALITY ASSURANCE ..................................... 107 
10.1 
AUDITS AND INSPECTIONS ......................................................................................... 107 
10.2 
STUDY MONITORING ................................................................................................. 107 
10.3 
QUALITY LABORATORY STANDARDS ....................................................................... 108 
10.4 
STUDY DOCUMENTATION .......................................................................................... 108 
10.4.1 Source Document ....................................................................................................... 109 
10.4.2 Recording of Data on Case Report Form (CRF) ....................................................... 109 
10.4.3 Investigator Site File .................................................................................................. 110 
10.5 
CLINICAL TRIAL SUPPLIES ....................................................................................... 110 
10.6 
DATA MANAGEMENT ................................................................................................ 110 
11. 
STUDY ADMINISTRATION................................................................................. 111 
11.1 
REQUIRED DOCUMENTS PRIOR TO STUDY INITIATION ........................................... 111 
11.2 
STUDY COMPLETION ................................................................................................. 111 
11.3 
CLINICAL STUDY REPORT (CSR) ............................................................................. 112 
11.4 
RETENTION OF STUDY RECORDS .............................................................................. 112 
11.5 
CONFIDENTIALITY AND PUBLICATION OF STUDY RESULTS .................................... 113 
11.5.1 General ....................................................................................................................... 113 
11.5.2 Published Data ........................................................................................................... 114 
12. 
REFERENCES ......................................................................................................... 115 
13. 
APPENDICES .......................................................................................................... 117 
 
LIST OF TABLES 
Table 1: 
Laboratory Assessments .............................................................................. 77 
Table 2:  
Injected Volume based on Patient’s Weight................................................ 82 
Table 3: 
Severity of Adverse Events According to CTCAE (Version 5) .................. 88 
Table 4: 
Relationship of Adverse Event to Treatment .............................................. 89 
Table 5: 
BL-8040-SCM.301 (GENESIS) Schedule of Assessments – Treatment 
Period ......................................................................................................... 117 
Table 6: 
BL-8040-SCM.301 (GENESIS) Schedule of Assessments – Post Treatment 
Period ......................................................................................................... 121 
  
TABLE OF FIGURES  
Figure 1: 
Stem Cell Mobilization Procedure .............................................................. 52 
 

 
 
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LIST OF APPENDICES 
Appendix A: 
Schedule of Assessments ........................................................................... 117 
Appendix B: 
Eastern Cooperative Oncology Group Performance Status ...................... 123 
Appendix C: 
International Myeloma Working Group (IMWG) Uniform Response Criteria
 ................................................................................................................... 124 
Appendix D: 
CIBMTR (Engraftment Guideline) ........................................................... 125 
 
  
 
 
 

 
 
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PROTOCOL SYNOPSIS 
Study Title 
A Phase III, Randomized, Double-Blinded, Placebo-Controlled, Multi-
Centre Study Evaluating the Safety, Tolerability and Efficacy of 
Combination Treatment of BL-8040 and G-CSF as compared to Placebo 
and G-CSF for the Mobilization of Hematopoietic Stem Cells for 
Autologous Transplantation in Subjects with Multiple Myeloma – 
The GENESIS Study 
Protocol No. 
BL-8040.SCM.301 
EudraCT: 
 
Clinical Sites 
Approximately 35 sites in the USA, Canada and Europe 
Study Phase 
III 
Therapeutic 
Indication 
Hematopoietic Stem Cell Mobilization for Autologous Transplantation in 
Subjects with Advanced Hematologic Malignancies (Multiple Myeloma 
(MM). 
Study 
Objectives 
Primary Objective: 
To demonstrate the superiority of one dose of BL-8040 + G-CSF over placebo 
+ G-CSF to mobilize ≥6.0 x 106 CD34+ cells/kg in up to 2 apheresis sessions 
in preparation for autologous hematopoietic cell transplantation (auto-HCT) in 
MM subjects. 
Secondary Objectives: 
• 
To demonstrate the superiority of one dose of BL-8040 + G-CSF over 
placebo + G-CSF to mobilize ≥2.0 x 106 CD34+ cells/kg in 1 apheresis 
session in preparation for autologous hematopoietic cell transplantation 
(auto-HCT) in MM subjects. 
• 
To demonstrate the superiority of one dose of BL-8040 + G-CSF over 
placebo + G-CSF to mobilize ≥6.0 x 106 CD34+ cells/kg in 1 apheresis 
session in preparation for autologous hematopoietic cell transplantation 
(auto-HCT) in MM subjects. 
• 
To descriptively assess the comparability between the effects of BL-8040 
+ G-CSF and placebo + G-CSF in time to neutrophil engraftment, platelet 
engraftment and the later of the two. 
• 
To descriptively assess the comparability between the effects of BL-8040 
+ G-CSF and placebo + G-CSF on graft durability at 60 days, 100 days, 
and 6 and 12-months post-transplantation. 
• 
To demonstrate that the use of (one or two doses) BL-8040 + G-CSF over 
placebo + G-CSF results in a reduction in resource use and cost savings. 
Exploratory Objectives: 
• 
To demonstrate the superiority of BL-8040 + G-CSF over placebo + G-
CSF in increasing CD34+ cell concentration in the peripheral blood on 
apheresis Day 1 or Day 1 and 2, if applicable. 
• 
To descriptively assess the comparability between the effects of BL-8040 
+ G-CSF and placebo + G-CSF in graft failure post-transplantation. 
• 
To descriptively assess the comparability between the effects of BL-8040 
+ G-CSF and placebo + G-CSF in overall survival with up to 5 years 
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Study 
Objectives 
• 
To descriptively assess the comparability between the effects of BL-8040 
+ G-CSF and placebo + G-CSF in relapse-free survival with up to 5 years 
follow-up. 
• 
To descriptively assess the comparability between the effects of BL-8040 
+ G-CSF and placebo + G-CSF in the mobilization of Multiple Myeloma 
cells in the apheresis product. 
• 
To descriptively compare the CD34+ cells collected per kg of actual body 
weight (ABW) used in this study to the theoretical amount of CD34+ cells 
collected based on ideal body weight (IBW) 
Safety and Tolerability Objectives: 
To demonstrate that the combination of BL-8040 + G-CSF is safe and tolerable 
as compared to Placebo + G-CSF. 
 
Pharmacokinetic Objectives: 
• 
BL-8040 exposure as measured by Cmax and AUC (See Section 5.6). 
• 
Effect of covariates such as body weight and age on BL-8040 exposure. 
• 
Exposure-response analysis, if warranted. 
 
Pharmacoeconomic Objectives: 
The resource utilization up until engraftment, 100 days after transplantation, 
multiplied with per country unit costs to obtain an average cost per patient per 
treatment arm. 
Study Design 
A randomized, double-blinded, placebo-controlled, multi-center, 2-part study 
to evaluate the effect of BL-8040 in combination with G-CSF on the collection 
of CD34+ cells for auto-HCT. 
This Phase III study will be composed of two sequential parts: 
Part 1: 
This lead-in period is designed to ascertain the dose of BL-8040 and will enroll 
a total of up to 30 subjects to an open labeled treatment to assess the efficacy, 
safety and tolerability of treatment with G-CSF 10 µg/kg/day and BL-8040 
1.25 mg/kg, per study protocol, to achieve the goal collection of ≥ 6 x 106 
CD34+ cells/kg. 
An independent data monitoring committee (DMC) will then assess the 
accumulated data of this lead-in period and recommend whether to continue to 
Part 2 of the study with BL-8040 1.25 mg/kg. The review of the accumulated 
data of Part 1 will be conducted in 3 sequential steps: 
• Initially, the accumulated data of 10 subjects will be summarized and 
reviewed by the DMC, which may recommend that Sponsor either study 
an additional cohort of 10 subjects, lower the dose, discontinue the study 
or continue to Part 2 of the study. 
• Similarly, after reviewing the accumulated data of a total of 20 subjects, 
the DMC may recommend that the Sponsor either study an additional 
cohort of 10 subjects, lower the dose, discontinue the study or continue 
to Part 2 of the study. 
• After reviewing the accumulated data of a total of 30 subjects, the DMC 
will make recommendations regarding study continuation. 

 
 
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Study Design  
The following decision rules will be taken into consideration by the DMC: 
• The primary efficacy endpoint of the study is the proportion (%) of 
subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to two apheresis 
sessions in preparation for auto-HCT after G-CSF + single 
administration of BL-8040 or Placebo + G-CSF. 
• After the review of the accumulated data of 10 subjects, enroll an 
additional 10 subjects if the number of subjects meeting the primary 
efficacy endpoint is less than or equal to 6. 
• After the review of the accumulated data of 20 subjects, enroll an 
additional 10 subjects if the number of subjects meeting the primary 
efficacy endpoint is less than or equal to 12. 
• After the review of the accumulated data of 30 subjects, a decision of 
early termination of the study should be taken if the number of subjects 
meeting the primary endpoint is less than or equal to 16. 
 
Furthermore, the DMC will have the freedom to employ more conservative 
decision rules based on integrative risk and benefit assessments of the 
accumulated information of the study at each decision point. 
All subjects treated during Part 1 will continue to be followed concomitantly to 
the conduct of Part 2 and according to the same visit schedule until study 
termination. 
 
Part 2: 
Following the successful completion of Part 1, a total of 177 subjects will be 
randomized into Part 2 of the study, which will employ a double-blinded, 
placebo-controlled design to assess the efficacy, safety and tolerability of BL-
8040 + G-CSF as compared to placebo + G-CSF. 
Subjects to be enrolled during Part 2 of the study will be randomized in a 2:1 
ratio to receive either BL-8040 or placebo, respectively, plus G-CSF. 
Randomization will be stratified based on remission status (Complete Remission 
(CR) vs. Partial Remission (PR))a and baseline platelet count (<200 x 109/L or ≥ 
200 x 109/L). The apheresis product will be processed and stored according to 
local practice guidelines at each study center. 
Subjects will undergo mobilization with G-CSF ~10 µg/kg (and maximum of 15 
µg/kg) subcutaneously (SC) daily in the morning (8:00AM ± 2 hours) for up to 8 
days. Beginning on the evening of Day 4 (8:00PM ± 2 hours), subjects will 
receive either a single injection of BL-8040 or placebo SC. In the morning of 
Day 5, a 5th dose of G-CSF will be administered within 1hr prior to apheresis (12 
hours ± 2 hours from BL-8040/placebo injection). Subjects will then undergo 
first apheresis per institutional protocol (4 blood volumes ±10% /apheresis). In 
the event that the subject does not reach the collection goal for mobilization 
(≥6.0 x 106 CD34+ cells/kg), on Day 6, a 6th dose of G-CSF will be administered 
within 1 hr prior to the second apheresis session (36 hours ± 2 hours from the 
BL-8040/placebo injection) in an effort to reach a total of ≥6 x 106 CD34+ 
cells/kg. 
 
a Response criteria for the purposes of study stratification will be defined in accordance with the International Myeloma 
Working Group (IMWG) Uniform Response Criteria see Appendix C.  Additionally, we will combine Stringent CR and CR 
into one “CR” group and VGPR and PR into one “PR” group. Partial Response (PR) including PR and Very Good PR (VGPR) 
and Complete Response (CR) which includes CR and Stringent CR (SCR) 

 
 
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Study Design  
If the subject does not reach the collection goal for mobilization (≥6.0 x 106 
CD34+ cells/kg), a second dose of BL-8040/placebo will be administered in the 
evening of Day 6 (48 hours ± 2 hours from the initial BL-8040/placebo 
injection). In the morning of Day 7, a 7th dose of G-CSF will be administered 
within 1 hr prior to the third apheresis session (12 hours ± 2 hours from the 
second BL-8040/placebo injection). If the subject still does not reach the 
collection goal for mobilization (≥6.0 x 106 CD34+ cells/kg), a fourth and final 
apheresis will be performed on Day 8 (36 hours ± 2 hours from the second BL-
8040/placebo injection), with an 8th dose of G-CSF administered within 1 hour 
prior to the apheresis, in an effort to collect a total of ≥6 x 106 CD34+ cells/kg, 
but at least ≥ 2 x 106 CD34+ cells/kg from the combined collections. Subjects 
who fail to collect the minimum required CD34+ cells/kg will be subsequently 
managed per investigator preference in accordance with standard of care 
guidelines to receive rescue medication. They may reattempt mobilization per 
standard of care after at least 7 day’s “rest/wash-out” period (7 days from the last 
dose of BL-8040/placebo). Subjects who fail to collect enough CD34+ cells in 
four apheresis sessions will continue to be followed according to the protocol 
schedule of visits. 
One interim analysis for potential early termination of new subject recruitment 
into the study will be conducted at the time when a total of 65% of the 
originally planned sample size will be randomized and have completed the 
stem cell mobilization procedure. 
Study 
Procedures 
Visit Procedures 
Screening (Day -28 to Day 0) 
From the time of Informed Consent Form (ICF) signature until Day 0 (Baseline 
Visit). 
During Screening, the subject must be thoroughly informed about all aspects of 
the study, including scheduled study visits and activities, and must sign the 
informed consent form (ICF) prior to any study activity. 
Prior to any study activities/evaluation, the subject will be allocated a subject 
number by the Investigator using an Interactive Web Response System (IWRS), 
which will be used throughout the study, and assessed for eligibility criteria. 
A window of up to 28 days is allowed for the screening period procedures. 
Urinary and blood laboratory assessments, as well as ECG, must be completed 
within 10 days (+2 days) before G-CSF administration, except blood serology, 
UPEP, SPEP, immunofixation and FLC. Potential subjects will be assessed for 
fulfilment of the entry requirements as detailed in the Inclusion and Exclusion 
criteria sections of the synopsis. 
The following procedures will be performed: 
• 
ICF process 
• 
Inclusion/exclusion criteria review 
• 
Collect demographics and medical history 
• 
Review prior and concomitant medications 
• 
Complete physical examination 
• 
IWRS 
• 
Adverse Events (AEs) recording starting from ICF signature 

 
 
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Study 
Procedures 
• 
12 lead electrocardiogram (ECG) 
• 
Vital signs (blood pressure, heart rate, respiratory rate, temperature [°C] 
and room air SPO2) 
• 
Eastern Cooperative Oncology Group (ECOG) performance status 
• 
Coagulation Test: Prothrombin Time (PT)/International Normalized 
Ratio (INR) and Activated Partial Thromboplastin Time (aPTT) 
• 
Complete Blood Count (CBC) with differential 
• 
Blood chemistry 
• 
Serum pregnancy test for all female patients of childbearing potential 
• 
Blood Serology Assessment 
• 
Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
• 
Monoclonal Protein (M) in urine (UPEP) and urine immunofixation-24 
hours urine collection is required 
• 
Serum Free Light Chain (FLC) 
• 
Urinalysis 
• 
Bone marrow biopsy – only for CR/sCR patients 
Subjects who fail the screening procedures may be re-screened. Re-screening 
should include all screening procedures listed in the protocol schedule of 
events, including re-consent signature. 
Of note: Screening Visit procedures can be performed on the same calendar day 
as Baseline Visit provided those are performed within 3 days before G-CSF 
administration. 
Baseline Visit, Day 0 (-3 days to Day 0) 
Baseline visit should occur within 28 days after the screening visit and within 3 
days prior to G-CSF administration. Only subjects who fully comply with the 
inclusion/exclusion criteria for the study will be eligible for participation. 
Of note: Baseline visit Day 0 and Visit Day 1 can be done on the same calendar 
day providing activities related to Baseline are done before G-CSF 
administration. 
The following procedures will be performed at the Baseline Visit. A window of 
three days (-3 days to Day 0) is allowed for the procedures and assessments of 
this visit: 
• 
AE recording 
• 
Inclusion/Exclusion criteria review 
• 
Concomitant Medications review 
• 
Directed Physical Examination (if Baseline Visit Day 0 and Visit Day 1 
are performed on the same day, Directed PE will be done prior to G-CSF 
administration) 
• 
Vital signs (supine blood pressure, heart rate, respiratory rate, 
temperature [°C] and room air SPO2) 
• 
12 Lead ECG 
• 
CBC with differential 
• 
Blood chemistry 

 
 
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Study 
Procedures 
• 
CD34+ enumeration in PB 
• 
Weight (in kg) 
• 
Height (in cm) 
• 
Pregnancy test – serum or urine for all female patients of childbearing 
potential 
 
Treatment Period 
Visit Days 1-3 
Morning (8:00AM ± 2 hrs): Subjects will undergo mobilization with G-CSF ~10 
µg/kg (dose will be calculated according to local SoC and should not exceed 15 
µg/kg) subcutaneously (SC). 
The following procedures will be performed: 
• 
AE recording 
• 
Concomitant Medications review 
• 
Resource use and cost element data collection only if G-CSF is 
administered at the site (in-patient) 
• 
Enrollment with IWRS on Day 1 onlya 
 
Visit Day 4 
Morning (8:00AM ± 2 hours): Subjects will undergo mobilization with G-CSF 
~10 µg/kg (dose will be calculated according to local SoC and should not exceed 
15 µg/kg) subcutaneously (SC). 
The following procedures must be done before G-CSF injection, unless 
otherwise specified. 
• 
AE recording 
• 
Concomitant Medications review 
• 
CBC with differential 
• 
Blood chemistry 
• 
CD34+ enumeration in PBb 
• 
Resource use and cost element collection (before and after G-SCF 
administration) 
• 
Randomization using IWRS (only during Part 2, after G-SCF 
administration) 
 
a During Part 1, the IWRS system will be used for eligibility confirmation and stratification parameters entry as no 
randomization is conducted in Part 1. During Part 2, the IWRS system will provide treatment allocation. 
b Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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Study 
Procedures 
Evening of Day 4 (8:00PM ± 2 hours): Subjects will receive either a single 
injection of BL-8040 1.25 mg/kg or placebo SC.  During Part 1, only BL-8040 
(no placebo) will be administered. Premedication should be administered within 
1 hour prior to BL-8040/Placebo administration. 
All evening procedures should be done before BL-8040/placebo injection, unless 
otherwise specified. 
 Directed Physical Exam 
 AE recording 
 Triplicate 12 Lead ECG: 
a. 
Pre-dose (up to 1 hour before BL-8040/placebo administration) 
and 
b. 
30-45 minutes post-dose 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature [°C] 
and room air SPO2) 
 CBC with differential 
 Blood draw for PK Assessment: 
a. 
Pre-dose (up to 1 hour before BL-8040/placebo administration) 
b. 
Post dosea (40-60 minutes and 2-6 hours) 
 Blood draw for ADA assessment: 
a. 
Pre BL-8040/Placebo dosing up to 1 hour before 
 Blood draw for assessment of Complement Activation 
a. 
Pre BL-8040/placebo dosing up to 1 hour before 
b. 
2 hours post dosinga ±15 minutes 
 Blood draw for assessment of serum tryptase (test for Mast Cell 
Activation) 
a. 
Pre BL-8040/placebo dosing up to 1 hour before dosing 
b. 
2 hours post dosinga ±15 minutes 
c. 
Only in case of anaphylaxis, unscheduled sample for tryptase 
will be collected within 2 hours from the event. 
Visit Day 5 
PK assessment 
Blood draw for PK assessment: 12 ± 2 hrs post second dose of BL-8040/Placebo 
administration and before apheresis 
 
Morning (8:00AM ± 2 hours): A 5th dose of G-CSF will be administered prior to 
first apheresis. Subjects will then undergo apheresis per institutional protocol (4 
blood volumes ±10%/apheresis). 
 
 
a Post dose defined as end time of administration 

 
 
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Study 
Procedures 
The following days of collections and treatments will be conducted provided the 
threshold of ≥6 x 106 CD34+ cells/kg for mobilizations was not reached: 
The below procedures should be done before G-CSF injection: 
 
Directed Physical Exam 
 
AE recording 
 
Concomitant Medications review 
 
Weight 
 
Triplicate 12 Lead ECG (up to 1 hour prior to G-CSF) 
 
Vital signs 
 
CBC with differential 
 
Coagulation test 
 
Blood chemistry 
 
CD34+ enumeration in PBa 
 
Resource use and cost element data collection (Part 2) 
 
The below procedures should be done after G-CSF injection: 
 
Apheresis - four blood volumes ±10% apheresis – (12 hours ± 2 hours 
post first dose of BL-8040/Placebo administration ) - See section 5.2.4 
 
CD34+ enumeration in apheresis producta 
 
Lymphocyte subsets in apheresis product (Part 2) 
 
Multiple Myeloma cells in the apheresis product (Part 2) 
 
Resource use and cost element data collection (Part 2) 
Visit Day 6 
This visit will be conducted only for: 
 
Subjects who did not reach the goal of collection of ≥6 x 106 CD34+ 
cells/kg for mobilization after one apheresis. 
 
All subjects with moderate or severe renal impairment at Screening as 
defined by GFR <50 mL/min/1.732 calculated by MDRD equation 
regardless of the amount of cells collected in the first apheresis. 
 
For all patients who did not reach the collection goal in the first apheresis, a 
6th dose of SC G-CSF ~10 µg/kg (and maximum of 15 µg/kg) will be 
administered prior to the second apheresis in an effort to reach a total of ≥6 x 106 
CD34+ cells/kg. The following procedures should be performed: 
Morning 8:00AM ± 2 hrs: Subjects will be administered with G-CSF ~10 µg/kg 
(and maximum of 15 µg/kg) SC 
 
a Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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Study 
Procedures 
The below procedures should be done before G-CSF injection: 
 
AE recording 
 
Concomitant Medications review  
 
CBC with differential 
 
Blood chemistry 
 
CD34+ enumeration in PBa 
 
Resource use and cost element data collection (Part 2) 
 
The below procedures should be done after G-CSF injection: 
 
Apheresis - four blood volumes ±10% apheresis - See section 5.2.4 
 
CD34+ enumeration in apheresis producta 
 
Lymphocyte subsets in apheresis product (Part 2) 
 
Multiple Myeloma Cells in the apheresis product (Part 2) 
 
Resource use and cost element data collection (Part 2) 
 
For subjects with moderate or severe renal impairment at Screening, as 
defined by GFR <50 mL/min/1.732 calculated by MDRD equation, the below 
procedures should be done: 
 
CBC with differential  
 
Blood chemistry 
 
Vital signs 
 
12 Lead ECG local assessment 
The results of serum creatinine and GFR, as well as any other clinically 
significant change, should be reviewed and assessed by the investigator. In case 
of abnormal clinically significant changes, it should be reported as AE and, in 
addition to the study procedures, subjects should be followed on a weekly basis 
until recovery or stabilization by the following procedures: 
 
Biochemistry with GFR assessment 
 
CBC with differential 
 
Vital signs 
 
12 Lead ECG local assessment 
 
AE assessment 
For subjects that did not reach the collection goal and present with 
BL-8040/placebo related clinically significant changes according to investigator 
assessment, a second administration will not be administered in the evening. The 
subjects will then be considered as early terminated and Visit 13 
(Termination/Early Termination) procedures should be followed. 
Of note: For patients with moderate or severe renal impairment at Screening, 
who also did not reach the collection goal, all of the above-listed procedures 
should be performed (CBC and biochemistry should be done only once). 
 
a Local assessment in both parts. For Part 2, sample will be analyzed at local central laboratory. 

 
 
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Study 
Procedures 
Only if the subject does not reach the collection goal for mobilization (≥6.0 x 
106 CD34+ cells/kg), a second dose of BL-8040/placebo (in Part 1, only BL-
8040 will be administered) will be administered in the evening.  
Evening (8:00PM ± 2 hrs): 
Premedication should be administered within 1 hour prior to BL-8040/Placebo 
administration. 
The below procedures should be done before BL-8040/placebo injection: 
 
Directed Physical Exam 
 
AE recording 
 
Triplicate 12 Lead ECG Day 4 evening: 
a. 
Pre-dose (up to 1 hour before BL-8040 administration) and 
b. 
30-45 minutes post-dose 
 
Vital signs 
 
CBC with differential 
 
IWRS for cases of a 2nd dose of BL-8040/Placebo 
 
Subjects will receive SC injection of BL-8040/placebo 
 
Blood draw for PK Assessment: 
a. Pre-dose (up to 1 hour before BL-8040/placebo administration) 
b. Post dosea (40-60 minutes and 2-6 hours) 
 
Resource use and cost element collection (Part 2) 
 
Visit Day 7 
This visit will be conducted only in subjects who did not reach the goal of 
collection after two apheresis procedures and received a second dose of BL-
8040/placebo on Visit Day 6. 
 
PK assessment 
Blood draw for PK assessment: 12 ± 2 hrs post second dose of BL-8040/Placebo 
administration and before apheresis  
 
Morning (8:00AM ± 2 hours): A 7th dose of SC G-CSF ~10 µg/kg (and 
maximum of 15 µg/kg) will be administered prior to a third apheresis. 
The below procedures should be done before G-CSF injection: 
 
Directed Physical Exam 
 
Review AE 
 
Concomitant Medications review 
 
Triplicate 12 Lead ECG  
 
Vital signs 
 
CBC with differential 
 
Coagulation Test 
 
Blood chemistry 
 
a   Post dose defined as end time of administration 

 
 
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Study 
Procedures 
 
CD34+ enumeration in PBa 
 
Resource use and cost element data collection (Part 2) 
 
The below procedures should be done after G-CSF injection: 
 
Apheresis - four blood volumes ±10% apheresis - 12 hours ± 2 hours 
post second dose of BL-8040/Placebo administration ) See section 5.2.4 
 
CD34+ enumeration in apheresis producta 
 
Lymphocyte subsets in apheresis product (Part 2) 
 
Multiple Myeloma Cells in the apheresis product (Part 2) 
 
Resource use and cost element data collection (Part 2) 
 
Visit Day 8 
This visit will be conducted only for: 
 
All subjects who did not reach the collection goal for mobilization 
(≥6.0 x 106 CD34+ cells/kg) after three apheresis procedures. In this 
case an 8th dose of G-CSF will be administered prior to fourth apheresis.  
 
All subject with moderate or severe renal impairment at Screening as 
defined by GFR of <50 mL/min/1.732 calculated by MDRD equation, 
who received a second dose of BL-8040/placebo, regardless of the 
amount of cells collected in the apheresis. 
 
For subjects who did not reach the goal of collection, the following 
procedures should be performed: 
Morning (8:00AM ± 2 hours): A 8th dose of SC G-CSF ~10 µg/kg (and 
maximum of 15 µg/kg) will be administered prior to a third apheresis. 
The below procedures should be done before G-CSF injection: 
 
Directed physical examination 
 
Review AEs 
 
Review of Concomitant medications 
 
Vital signs 
 
CBC with differential 
 
Blood chemistry 
 
CD34+ enumeration in PBa 
 
Resource use and cost element data collection (Part 2) 
 
a Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory.  

 
 
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Study 
Procedures 
The below procedures should be done after G-CSF injection: 
 
Apheresis - four blood volumes ±10% apheresis 
 
CD34+ enumeration in apheresis producta 
 
Lymphocyte subsets in apheresis product (only during Part 2) 
 
Multiple Myeloma Cells in the apheresis product (only during 
Part 2) 
 
Resource use and cost element data collection (Part 2) 
 
For subjects with moderate or severe renal impairment at Screening as 
defined by GFR of <50 mL/min/1.732 calculated by MDRD equation, the below 
procedures should be done: 
 
CBC with differential 
 
Blood chemistry 
 
Vital signs 
 
12 Lead ECG local assessment 
The results of serum creatinine and GFR, as well as any other clinically 
significant change, should be reviewed and assessed by the investigator. In case 
of abnormal clinically significant changes, it should be reported as AE and in 
addition to the study procedures, subjects should be followed on a weekly basis 
until recovery or stabilization by the following procedures: 
 
Biochemistry with GFR assessment 
 
CBC with differential 
 
Vital signs 
 
12 Lead ECG local assessment 
 
AE assessment 
 
Rescue procedure 
Subjects who fail to collect the cells required per local SoC after four apheresis 
sessions will be managed per investigator preference in accordance with 
standard of care guidelines. They may re-attempt mobilization per standard of 
care after at least 7 days’ “rest/wash-out” period from the last dose of BL-
8040/placebo. Subjects who failed to collect enough CD34+ cells in four 
apheresis sessions will continue to be followed according to the protocol 
schedule visits. 
All cost element and resource use related to rescue procedure will be collected 
and captured in the eCRF. 
 
 
a Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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Study 
Procedures 
Visit 9: Conditioning Treatment Pre-Transplantation 
Following successful mobilization and collection of adequate CD34+ cells for 
auto-HCT, study participants will be admitted to the hospital for preparative 
(conditioning) chemotherapy. Conditioning must occur within 5 weeks after the 
last apheresis session 
The procedures and evaluations at Visit 9 should be done within 3 days before 
beginning of conditioning. 
The pre-transplant conditioning chemotherapeutic regimens (± total body 
irradiation (TBI)) used in this trial may include: 
 
Melphalan (200 or 140 mg/m2) 
 
BEAM 
 
BuCy 
 
Arsenic/Melphalan 
 
Busulfan/Melphalan 
Selection of the appropriate conditioning regimen shall be at the discretion of 
the Investigator. Local Standard of Care guidelines will be followed. 
The procedures and evaluations at Visit 9 should be done within 3 days before 
beginning of conditioning: 
 Complete Physical Exam 
 Concomitant Medications review 
 Vital signs 
 CBC with differential  
 Blood Chemistry 
 Blood draw for ADA assessment 
 Pregnancy test (urine/serum) 
 Resources use and cost elements data collection 
 
Visit 10: Transplantation and Immediate Post-Transplantation Follow-Up 
 
Transplantation will occur ~24 hours following the completion of the 
conditioning regimen and no later than 5 weeks after the last apheresis session. 
Transplantation should be performed using the collected CD34+ cells. A 
minimum of >2x106 CD34+ cells/kg must be transplanted; however, more cells 
may be transplanted up to the full amount collected at the Investigator’s 
discretion. Excess CD34+ cells may be stored for later use, per Investigator 
preference. 
Local guidelines for transplantation will be followed. 
Post-transplantation follow-up begins the day after cell transplantation and lasts 
until the time of neutrophil and platelet engraftment (whichever comes later). 
This will be assessed by daily CBC of PB (unless engraftment period is 
conducted as an outpatient - in that case only neutrophils and platelets count will 
be collected and documented in the CRF together with any usage of medications 
during this period). 

 
 
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Study 
Procedures 
Engraftment is defined as: 
• 
Neutrophil engraftment: Defined as the first of 3 consecutive days of 
ANC ≥0.5 x 109/L or ≥1.0 x 109/L for 1 day following the conditioning-
regimen-associated nadir. 
• 
Platelet engraftment: Defined as the first of 3 consecutive measurements 
of platelet count ≥20 x 109/L following the conditioning regimen 
associated nadir and without platelet transfusion support for 7 days 
• 
Of note: For subjects receiving transfusion for any reason other than 
platelet count <20 x 109/L, who already met the platelet engraftment 
criteria as above, this transfusion will not affect the platelets 
engraftment assessment date (e.g. transfusion for any specific 
procedures or as part of  SoC in specific institutions, etc.) 
• 
Actual engraftment days will be calculated according to CIBMTR 
guidelines (See Appendix D). 
 
The procedures and evaluations at Visit 10 are as follows: 
Day of transplantation - Before Transplant: 
 Directed Physical Exam 
 Concomitant Medications review 
 Vital signs 
 CBC with differential 
 Blood chemistry 
 Resource use and cost elements data collection 
 
Day 1-29 post-transplant: 
Procedures to be done daily beginning the day after transplantation until 
engraftment: 
 Neutrophil and platelets assessment 
a. For in-patient, CBC with differential will be collected daily and 
recorded accordingly until engraftment 
b. For patient that are followed up as out-patient, assessment will 
be done according to local SoC and recorded within the CRF 
 Recording administration of G-CSF, other growth factors or blood and 
platelets transfusion will be fully documented within CRF 
Resources use and cost elements data collection (only for inpatients) 
 
Visits 11-16 
Following transplantation, subjects will be monitored for graft durability in PB 
on the following visit days: 
 Visit 11: Day 30 Post Transplantation (±3 days) 
 Visit 12: Day 60 Post Transplantation (±7 days) 
 Visit 13: Day 100 Post Transplantation, Termination/ Early Termination 
(± 7 days) 

 
 
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Study 
Procedures 
Long Term Assessment Follow-up Post Transplantation 
 Visit 14: Day 180 (6 months) Post Transplantation (± 14 days) 
 Visit 15: Day 270 (9 months) Post Transplantation (± 14 days) 
 Visit 16: Day 360 (12 months) Post Transplantation (± 14 days) 
 
Graft durability is defined as maintenance of at least 2 of the following 3 
criteria: 
• 
Platelet count ≥50,000 (50 x 109/L) without transfusion for at least 2 
weeks. 
• 
Hemoglobin level ≥10 g/dL with no erythropoietin support or 
transfusions for at least 1 month.  
• 
Absolute neutrophil count (ANC) ≥1,000 (1.0 x 109/L) for 1 week. 
 
Bone marrow biopsy will be performed on Day 100 (Visit 13) if there is no 
biochemical evidence of relapse. 
 
Visit 11 – Day 30 Post Transplantation (±3 days) 
The procedures and evaluations will be as follows: 
 Concomitant Medications review- only disease related medications should 
be reported. 
 Vital signs 
 CBC with differential 
 Blood chemistry 
 Blood Draw for ADA 
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation-24 
hours urine collection is required 
 Serum Free Light Chain (FLC) 
 Engraftment assessment by platelets and neutrophils count 
 Resource use and cost elements data collection (only during Part 2) 
 
Visit 12, Day 60 Post Transplantation (±7 days) 
The procedures and evaluations will be as follows before starting maintenance 
therapy and will include: 
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation-24 
hours urine collection is required 
 Serum Free Light Chain (FLC) 
 Concomitant Medications review-only disease related medications should 
be captured. 
 Vital signs 
 ECOG performance status (see Appendix B) 
 CBC with differential 

 
 
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Study 
Procedures 
 Blood chemistry 
 Relapse Free Survival (RFS) and overall survival (OS) assessment 
 Resource use and cost elements data collection (only during Part 2) 
 
Maintenance Treatment 
Subjects can receive maintenance treatment with lenalidomide, bortezomib, 
pomalidomide or a similar FDA-approved maintenance therapy, beginning on 
Day 60 Post Transplantation, and according to institute standard of care. Patients 
should not receive maintenance therapy within the first 60 days from 
transplantation, except in the case of confirmed disease relapse. Data should be 
recorded within the CRF in a dedicated page for maintenance treatment. 
 
Visit 13: Day 100 Post Transplantation, Termination/ Early Termination Visit 
(±7 days) 
Termination visit procedures: 
 Review of concomitant medications (only disease related medications 
should be captured) 
 Complete physical examination 
 Vital signs 
 ECOG performance status 
 CBC with differential 
 Blood chemistry 
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation - 24 
hours urine collection is required 
 Serum Free Light Chain (FLC) 
 Bone marrow biopsy will be performed on Day 100 (Visit 13) if there is 
no biochemical evidence of relapse. Relapse Free Survival (RFS) and 
overall survival (OS) assessment 
 Resource use collection and cost elements data collection (only during 
Part 2) 
In case of early termination, an Early Termination visit will be performed, and 
the data will be captured at the termination visit page (Visit 13) of the CRF. All 
information for early termination, will be documented in the source documents. 
Only one reason (the most relevant) for early should be recorded in the CRF. If 
one of the reasons for discontinuation is an AE, this should be chosen as the 
reason. Patients who discontinue study treatment will continue to be followed as 
per protocol, unless they specifically withdrew consent for follow-up. Every 
effort should be made to follow-up these subjects until the end of the study 
period and certainly until the resolution of the AE. 
Data collection at these visits should primarily be guided by the need to protect 
subject safety and well-being. 

 
 
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Study 
Procedures 
In case the subject decides to discontinue the follow-up, the reason for 
discontinuation should be reported at the relevant CRF visit page. 
A patient who received G-CSF and discontinued before receiving BL-8040 
could potentially be rescreened assuming wash-out period from G-CSF is 
completed.  
Long Term Disease Assessment Follow-Up 
Visits 14-16: Day 180 (6 months) - Day 360 (12 months) 
Visits 14-16 will be conducted at 180 days (± 14 days), 270 days (± 14 days) and 
360 days (± 14 days) post transplantation, respectively, in order to assess graft 
durability and disease status. Visit procedures will include: 
 ECOG performance status 
 CBC with differential 
 Blood chemistry 
 Review of concomitant medications (only disease related medications 
should be captured) 
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation-24 
hours urine collection is required 
 Serum Free Light Chain (FLC) 
 Relapse Free Survival (RFS)/Overall Survival (OS) assessment  
 
Visits 17 and up to 5 years follow-up: Overall Survival (OS) Follow-Up 
After completing 12 months follow-up visits, subjects will be contacted by 
phone every 6 months (±30 days) in order to assess disease status for 
concomitant medications (only disease-related medications should be captured)  
and assessment for Relapse Free Survival (RFS) and Overall Survival (OS), 
beginning in Visit 17 at 18 months until 5 years from last patient randomization 
day. 
Each visit will be performed at a time window of ±30 days 
Study Duration 
It is expected that the entire study will last for approximately 7.5 years, which 
comprise: 
• 
Part 1: Depending on the number of subjects recruited during Part 1 (10 
to 30 subjects), it is estimated that Part 1 will last up to 6 months. 
• 
Part 2: The core study recruitment is estimated to take 18-24 months and 
the study will be concluded at 5 years after the last patient randomization 
day. 
Planned 
Sample Size 
A total of up to 207 subjects will be enrolled into the study: 
• 
Period 1 (Part 1) – Will enroll up to 30 subjects. 
• 
Period 2 (Part 2) – Will additionally randomize a total of 177 subjects. 

 
 
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Inclusion 
Criteria 
1. Patients must be between the ages of 18 and 78 years. 
2. Patients must have a signed study informed consent prior to entering the 
study. 
3. Histologically confirmed Multiple Myeloma prior to enrollment 
4. At least one week (7 days) from last induction cycle of 
combination/multi-agent chemotherapy (e.g. KRD [carfilzomib, 
lenalidomide, dexamethasone] or VRD [bortezomib, lenalidomide, 
dexamethasone]) or  from last single agent chemotherapy (e.g. 
lenalidomide, pomalidomide, bortezomib, dexamethasone, etc) prior to 
the first dose of G-CSF for mobilization. 
5. Eligible for Autologous Hematopoietic stem cell transplantation 
according to the Investigator’s discretion. 
6. The subjects should be in first or second CR (including CR and SCR) or 
PR (including PR and VGPR). 
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 
8. Adequate organ function at screening as defined below: 
a. Hematology: 
• White blood cell counts more than 2.5 x 109/L 
• Absolute neutrophil count more than 1.5 x 109/L 
b. Platelet count more than 100 x109/L Renal Function: 
• GFR value of ≥15 mL/min/1.732 calculated by MDRD equation 
c. Hepatic function: 
• ALT and/or AST ≤ 2.5 x ULN 
• Total Bilirubin ≤ 2.0 x ULN unless the subject has Gilbert disease 
d. Coagulation test: 
• INR or PT: ≤1.5xULN unless subject is receiving anticoagulant 
therapy, as long as PT or PTT is within therapeutic range of 
intended use of anticoagulants 
• aPTT: ≤1.5xULN unless subject is receiving anticoagulant 
therapy, as long as PT or PTT is within therapeutic range of 
intended use of anticoagulants 
9. 
Female subjects must be of non-childbearing potential or, if of 
childbearing potential, must have a negative serum pregnancy test at 
screening and negative urine/serum pregnancy test within 72 hours prior to 
G-CSF first administration. 
10. Women of childbearing potential must agree to use 2 methods of effective 
contraception: One barrier method (e.g. diaphragm, or condom or sponge, 
each of which are to be combined with a spermicide) and one hormonal 
method, unless she uses a highly effective method. Highly effective 
methods of contraception include: 
• Combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation: oral, 
intravaginal, transdermal 
• Progestogen-only hormonal contraception associated with inhibition 
of ovulation: oral, injectable, implantable 
• Intrauterine device (IUD) 

 
 
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Inclusion 
Criteria 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomised partner 
• Sexual abstinence 
These methods must be used prior to study entry and for the duration of 
study participation through 30 days after the last dose of study treatment. 
Non-childbearing potential is defined as (by other than medical reasons): 
• ≥45 years of age and has not had menses for over 2 years. 
• Amenorrheic for > 2 years without a hysterectomy and oophorectomy 
and a Follicle Stimulating Hormone (FSH) value in the 
postmenopausal range upon pre-trial (screening) evaluation. 
• Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy 
or bilateral tubal ligation at least 6 weeks prior to screening. 
Documented hysterectomy or oophorectomy must be confirmed with 
medical records of the actual procedure or confirmed by ultrasound. 
Tubal ligation must be confirmed with medical records of the actual 
procedure; otherwise the subject must be willing to use two adequate 
barrier methods throughout the study, starting with the Screening 
Visit, through 30 days after the last dose of study drug. Information 
must be captured appropriately within the site's source documents. 
11. Male subjects must agree to use an adequate method of contraception 
starting with the first day of G-CSF administration through 30 days after 
the last dose of study drug. 
Exclusion 
criteria 
1. Previous history of autologous or allogeneic-HCT. 
2. Failed previous HSC collections or collection attempts. 
3. Taken any of the listed below concomitant medications, growth factors or 
stimulating agents within the designated washout period: 
a. Dexamethasone: 7 days 
b. Thalidomide: 7 days 
c. Lenalidomide: 7 days 
d. Pamolidomide: 7 days 
e. Bortezomib: 7 days 
f. Carfilzomib: 7 days 
g. G-CSF: 14 days 
h. GM-CSF or Neulasta®: 21 days 
i. 
Erythropoietin or erythrocyte stimulating agents: 30 days 
j. 
Eltrombopag, romiplostim or platelet stimulating agents: 30 
days 
k. Carmustine (BCNU): 42 days/6 weeks 
l. 
Daratumumab: 28 days 
m. Ixazomib: 7 days 
4. Received >6 cycles lifetime exposure to thalidomide or lenalidomide. 
5. Received >8 cycles of alkylating agent combinations 
6. Received > 6 cycles of melphalan. 
7. Received prior treatment with radioimmunotherapy, (e.g. radionuclides, 
holmium). 
8. Received prior treatment with venetoclax 

 
 
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Exclusion 
criteria 
9. Plans to receive maintenance treatment within 60 days post- transplantation (e.g. 
lenalidomide, bortezomib, pomalidomide, thalidomide, carfilzomib, etc.). 
10. Has received a live vaccine within 30 days of the planned start of G-CSF 
administration. Seasonal flu vaccines that do not contain live virus are permitted. 
11. Known active CNS metastases or carcinomatous meningitis. 
12. A history of allergic reactions attributed to compounds of similar chemical or 
biologic composition to BL-8040, G-CSF, or other agents used in the study. 
13. Has an active or uncontrolled infection requiring systemic therapy. 
14. Has a known additional malignancy that is progressing or requires active 
treatment. 
15. Has an underlying medical condition that would preclude study participation. 
16. Is currently participating and receiving study therapy or has participated in a study 
of an investigational agent and received study therapy or used an investigational 
device within 4 weeks of the first dose of treatment. 
17. O2 saturation < 92% (on room air). 
18. Personal history or family history of Long QT Syndrome or Torsade de Pointes 
19. History of unexplained syncope, syncope from an uncorrected cardiac etiology, or 
family history of sudden cardiac death. 
20. Myocardial infarction, CABG, coronary or cerebral artery stenting and/or 
angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure 
within 3 months, Angina Pectoris Class >2 or NYHA Heart Failure Class >2. 
21. ECG at screening showing QTcF > 470 msec and/or PR > 280 msec. 
22. Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or 
Complete Heart Block, unless the patient has an implanted pacemaker or 
implantable cardiac defibrillator (ICD) with backup pacing capabilities. 
23. Has a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the trial, interfere with the subject’s 
participation for the full duration of the trial, or is not in the best interest of the 
subject to participate, in the opinion of the treating Investigator. 
24. Has known psychiatric or substance abuse disorders that would interfere with 
cooperation with the requirements of the trial. 
25. Is pregnant or breast feeding or expecting to conceive or women of childbearing 
potential unless consent to use two contraceptive methods or highly effective 
contraception as detailed above, within the projected duration of the trial, starting 
with the Screening Visit through 30 days after the last dose of study drug. 
26. Has a known history of HIV (HIV 1/2 antibodies). 
27. Has known active Hepatitis B (e.g., Hepatitis B Surface Antigen [HBsAg] 
reactive) or Hepatitis C (e.g., Hepatitis C Virus [HCV] RNA [qualitative] is 
detected). 
28. Untreated or unsuccessfully treated Hepatitis B or C. 

 
 
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Concomitant 
Medications 
Acceptable Concomitant Medications: 
• 
All treatments that the Investigator considers necessary for a subject’s 
welfare may be administered at the discretion of the Investigator in 
keeping with the community standards of medical care. If changes occur 
during the trial period, documentation of drug dosage, frequency, route, 
and date should also be included in the CRF. Starting from Visit 11 and 
onwards, only disease related medication data will be collected. 
• 
All medications and/or nutritional supplements/therapies taken by 
patients for the duration of study participation will be recorded in the 
patients’ records and transcribed into the CRF as follows: 
Documentation of concomitant medications will begin a year prior to 
screening. Subsequently, patients will be monitored for concomitant 
medications from the time of the first dose of G-CSF for mobilization 
until transplantation (inclusive). After transplantation, concomitant 
medications taken during and between each visit will be recorded only if 
G-CSF, erythropoietin, alternative stimulating agents and/or transfusions, 
and/or myeloma-related medications were given, in order to identify any 
possible medications that may be associated with bone marrow 
suppression or graft dysfunction. 
• 
G-CSF, erythropoietin, alternative stimulating agents and/or transfusions 
should be reported from the screening and up until 100 days post 
transplantation. 
Prohibited Concomitant Medications/Therapies: 
Subjects are prohibited from receiving the following therapies during the 
Screening period and Treatment Period of this trial: 
• 
Those listed previously in the Exclusion Criteria 
• 
Antineoplastic systemic chemotherapy or biological therapy 
• 
Chemotherapy not specified in this protocol 
• 
Investigational agents other than BL-8040 
• 
Radiation therapy: radiation therapy to a solitary symptomatic lesion 
may be considered on an exceptional case by case basis after 
consultation with the Sponsor. 
• 
Maintenance treatment with lenalidomide, bortezomib, pomalidomide, 
thalidomide, carfilzomib, etc. within 60 days post- transplantation. 
If there is a clinical indication for any medication specifically prohibited during 
the trial, it should be discussed with the Sponsor’s Medical Monitor. Subjects 
may receive other medications that the Investigator deems to be medically 
necessary. 
There are no prohibited therapies after the 60 days post- transplantation, during 
the Post-Treatment period Long Term Disease Assessment Follow-up. 

 
 
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Concomitant 
Medications 
Pre-Dose Medication and General Injection Instructions: 
• 
Premedication with an antihistamine is required for all patients, within 
one hour prior to study drug administration.  The time of administration 
of premedication is to be recorded on site documentation and in the CRF.  
The preferred route for administration of premedication is IV. 
The recommended premedication regimen is: H1 blocker (e.g 
diphenhydramine, Promethazine, etc) + H2 blocker (e.g. famotidine, 
ranitidine, etc) + leukotriene inhibitor (e.g. montelukast).  This triple-
drug combination is required prior to the first dose of BL-8040. 
• 
Analgesic medication may be added to the premedication regimen at the 
discretion of the treating physician. 
• 
BL-8040 is to be administered at a dose of 1.25 mg/kg by slow 
subcutaneous injection of at least 2 minutes per syringe.  If the volume to 
be administered exceeds 2 mL then the injection should be divided into 
two or more syringes to be administered at different injection locations. 
• 
Transient hypotension was witnessed in several cases following the 
initial treatment with BL-8040. Therefore, caution should be taken with 
the use of negative chronotropic drugs such as beta blockers. When 
appropriate, beta blocker should be replaced with non-negative 
chronotropic drugs. 
• 
All patients are to remain under surveillance for 2 hours after the first 
administration of BL-8040. Patients receiving an additional dose of BL-
8040 should remain under observation for 1 hour after the subsequent 
administration of BL-8040. 
• 
BL-8040 should only be administered when personnel and therapies 
are immediately available for the treatment of anaphylaxis and 
other hypersensitivity reactions, should they occur. 
Study 
Endpoints 
Primary Efficacy Endpoint 
Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 
apheresis sessions in preparation for auto-HCT after single administration of BL-
8040 + G-CSF or placebo + G-CSF. 
Secondary Efficacy Endpoints 
• 
Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis 
session. 
• 
Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis 
session. 
Additional Secondary Efficacy Endpoints 
The comparability between the effects of BL-8040 + G-CSF and placebo + G-
CSF with the below endpoints will be assessed in a descriptive manner: 
• 
Time from transplantation to neutrophil engraftment, defined as ANC ≥0.5 x 
109/L for 3 consecutive days or ≥1.0 x 109/L for 1 day following the 
conditioning regimen associated nadir. 
• 
Time from transplantation to platelet engraftment, defined as the first of 3 
consecutive measurements of platelet count ≥20 x 109/L without platelet 
transfusion support for 7 days following the conditioning regimen associated 
nadir. 

 
 
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Study 
Endpoints 
• 
Time from transplantation to engraftment, defined as the time to neutrophils 
and platelets engraftment, whichever comes later. 
• 
Graft durability at 60 days post-transplantation. 
• 
Graft durability at 100 days post-transplantation. 
• 
Graft durability at 6 months post-transplantation. 
• 
Graft durability at 12 months post-transplantation 
 
Exploratory Endpoints 
• 
Change from Baseline in peripheral blood CD34+ cell concentration on 
apheresis Day 1 or Day 1 and Day 2, if applicable, after BL-8040/placebo 
administration.  
• 
Incidence of graft failure post-transplant 
• 
Overall Survival (OS) during the period of up to 5 years. 
• 
Relapse-Free Survival (RFS) during the period of up to 5 years. 
• 
Mobilization of Multiple Myeloma cells assessed in the apheresis product 
after BL-8040/placebo administration. 
• 
CD34+ cells collected per kg of actual body weight (ABW) compared to 
theoretical amount of cells collected based on ideal body weight (IBW) 
Exploratory Biomarkers 
• 
Immunophenotyping of lymphocyte subsets in apheresis product. 
Safety and Tolerability 
• 
Incidence of AEs, defined and graded according to the NCI-issued Common 
Terminology Criteria for Adverse Events (CTCAE). 
• 
Incidence of early discontinuation and early discontinuation due to adverse 
events. 
 
Pharmacokinetic Endpoint 
• 
BL-8040 exposure as measured by Cmax and AUC (See Section 5.7). 
• 
Effect of covariates such as body weight and age on BL-8040 exposure. 
• 
Exposure-response analysis, if warranted. 
Pharmacoeconomic endpoint 
The resource utilization up until engraftment, 100 days after transplantation, 
multiplied with per country unit costs to obtain an average cost per patient 
per treatment arm. 

 
 
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Statistical 
Methodology  
General: 
This Phase III study was designed to meet two sequential goals. In Part 1 of the 
study, a total of up to 30 subjects will be enrolled to an open-labeled treatment 
with G-CSF followed by BL-8040 1.25 mg/kg, with the aim of ensuring that 
1.25 mg/kg is the optimal BL-8040 dose. This part will be conducted in 3 
sequential steps of 10 subjects each and the accumulated data at each step will be 
reviewed by an independent DMC. 
Following the successful completion of Part 1, a total of 177 subjects will be 
randomized into Part 2 of the study, which will employ a double-blind placebo-
controlled design to assess the safety, tolerability and efficacy of BL-8040 + G-
CSF as compared to Placebo + G-CSF. 
One interim analysis for potential early termination of new subject recruitment 
into the study will be conducted at the time when a total of 65% of the originally 
planned sample size will be randomized and have completed the stem cell 
mobilization procedure. 
Randomization: 
Following the successful completion of Part 1, subjects will be randomized using 
a 2:1 ratio to receive BL-8040 + G-CSF or Placebo + G-CSF, respectively. 
Randomization will use permuted blocks stratifying subjects by remission status 
(CR or PR) and baseline platelet count (<200 x 109/L or ≥200 x 109/L). 
Interim Analysis, Type-I Error and Multiplicity Adjustment: 
The overall alpha level for this study is 0.05 using 2-tailed tests. All significance 
testing for this study will use two-tailed tests. 
One interim analysis for potential early termination of new subject recruitment 
into the study will be conducted at the time when a total of 65% of the originally 
planned sample size will be randomized and have completed the stem cell 
mobilization procedure. 
For the interim analysis, treatment effect will be considered statistically 
significant if the p-value will be 0.0108678 or less. As the interim analysis will 
be conducted only for potential early termination of new subject recruitment into 
the study, the final analysis of primary and secondary endpoints, which will be 
conducted at the Core Study Termination Visit (Visit 13) that will occur at Day 
100 following transplantation (or early terminated before), will require a p-value 
of 0.0466256. These p-values represent the use of the Lan-DeMets’ correction to 
type-I error. 
Furthermore, one (1) primary endpoint and 2 secondary endpoints are pre-
defined for this study. Hence, there will be a total of 3 comparisons for the 
primary and secondary endpoints altogether. The hierarchical method for 
multiple endpoint testing for the secondary endpoints will utilize the gate 
keeping approach at alpha=0.0466256, ensuring that the overall experiment-wise 
type-I error of 5% is preserved. 

 
 
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Statistical 
Methodology  
 
Sample Size Justification for Part 1 (Open Labelled Period for ascertaining 
the BL-8040 dose optimization): 
To ascertain the dose of BL-8040, a total of up to 30 subjects will be enrolled to 
Part 1 of the study. The population size of Part 1 was determined based on the 
following assumptions: 
 
The endpoint to be used in order to ascertain the BL-8040 dose will be 
the proportion (%) of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg 
with up to 2 apheresis sessions in preparation for auto-HCT after G-
CSF + single administration of BL-8040. 
 
It is assumed that the proportion (%) of subjects mobilizing ≥6.0 x 106 
CD34+ cells/kg with up to 2 apheresis sessions due to treatment with 
BL-8040 + G-CSF will be 70% or more. 
 
Based on DiPersio JF, et al. Blood. 2009;113(23):5720-5726, it is 
assumed that the null reference hypothesis to be overcome is 35.3%. 
 
Using SAS® PROC POWER for one binomial proportion at a two-sided alpha 
level of 5%, we determined that a total of 24 subjects will provide 95% power to 
demonstrate superiority over the reference value of 35.3%. To account for 
potential dropouts, the Part 1 population size is further increased to a total of 30 
subjects. 
 
Sample Size Justification for Part 2 (Randomized, Placebo-Controlled 
Part): 
The power and the derived sample size for Part 2 of the study were calculated 
based on the following assumptions: 
 
The primary study endpoint is the proportion (%) of subjects 
mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions 
in preparation for auto-HCT after G-CSF + single administration of 
BL-8040 or Placebo + G-CSF. 
 
Subjects will be randomized to treatment with BL-8040 + G-CSF or to 
Placebo + G-CSF using a 2:1 randomization ratio, respectively. 
 
It is assumed that success rates for mobilizing ≥6 x 106 cells/kg in MM 
subjects following treatment with Placebo + G-CSF will be 35%. 
 
It is also expected that treatment with BL-8040 will result in a success 
rate of 70%, in line with results obtained for subjects treated with 
Mozobil + G-CSF. However, as a worst-case scenario, it is assumed 
that 20% of subjects assigned to the BL-8040 + G-CSF group would 
not get their assigned treatment and therefore, using the intention-to-
treat (ITT) principle, this would reduce the BL-8040 success rate to 
63%. 

 
 
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Statistical 
Methodology  
 
 
An additional attrition rate of 20% has also been taken into 
consideration. 
 
Final analysis will employ an alpha level of 0.0466256. 
 
SAS® PROC POWER for two proportions was used to determine the 
sample size.   
According to the above underlying assumptions, a total of 177 subjects will 
provide 89.8% power to demonstrate that treatment with BL-8040 + G-CSF is 
superior, at a two-sided alpha of 0.0466256, to treatment with Placebo + G-CSF 
in the study primary endpoint. 
The power at interim analysis, assuming an attrition rate of 20% and success 
rates of 70% and 35% for BL-8040 + G-CSF or Placebo + G-CSF, respectively, 
is 85.9%. 
 
Primary Endpoint and Principal Statistical Analysis: 
The primary study endpoint is the proportion (%) of subjects mobilizing ≥6.0 x 
106 CD34+ cells/kg with up to 2 apheresis sessions in preparation for auto-HCT 
after G-CSF + single administration of BL-8040 or Placebo + G-CSF. 
The following rules will be incorporated to derive this endpoint: 
 
Only subjects randomized to study treatment during Part 2 of the study will 
be included in the formal efficacy analysis. 
 
A subject who cumulatively mobilizes ≥6.0 x 106 CD34+ cells/kg with up 
to 2 apheresis sessions will be classified as a “Responder”. 
 
Other subjects, including randomized subjects who failed to complete the 
stem cell mobilization procedure, as well as those who did not mobilize 
6.0 x 106 CD34+ cells/kg after up to 2 apheresis sessions, will be classified 
as “Non-Responders”. 
The principal analysis of this binary endpoint will use the Cochran-Mantel-
Haenszel test stratified by remission status (CR or PR) and baseline platelet 
count (<200x109/L or ≥200x109/L). 
 
Sequence of Planned Analyses: 
Study enrollment may early be terminated in the case that interim analysis will 
provide statistically significant (p<0.0108678) evidence favoring treatment with 
BL-8040 + G-CSF. Otherwise, study will continue to randomize up to 177 
subjects. 
The sequence of the planned statistical analyses for this study is described below 
in chronological order: 
Initially, the interim analysis will be conducted at the time when a total of 65% 
of the planned sample size will be randomized and have completed the stem cell 
mobilization procedure. A detailed statistical analysis plan (SAP) will be 
developed while the study is blinded, prior to the conduct of interim analysis. 
The results obtained for this analysis will be used only to determine if study 
enrollment is to be halted. 

 
 
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Statistical 
Methodology  
 
Thereafter, the core set of the study accumulated data will be made available for 
statistical analyses on the day that the last study randomized subject completes 
the Core Study Termination Visit (Visit 13), which will occur at his/her Day 100 
following transplantation (or if early terminated before). At that time the study 
database will be locked and a formal statistical analysis of the following 
endpoints will be conducted: 
 
Primary Endpoint: Proportion of subjects mobilizing ≥6.0 x 106 CD34+ 
cells/kg with up to 2 apheresis sessions in preparation for auto-HCT after a 
single administration of BL-8040 + G-CSF or placebo + G-CSF. 
 
Secondary Endpoint: Proportion of subjects who collect ≥2.0 x 106 CD34+ 
cells/kg in 1 apheresis session. 
 
Secondary Endpoint: Proportion of subjects who collect ≥6.0 x 106 CD34+ 
cells/kg in 1 apheresis session. 
 
Additional Secondary Endpoint: Time to neutrophil engraftment, defined as 
ANC ≥0.5 x 109/L for 3 consecutive days or ≥1.0 x 109/L for 1 day 
following the conditioning regimen associated nadir. 
 
Additional Secondary Endpoint: Time to platelet engraftment, defined as 
the first of 3 consecutive measurements of platelet count ≥20 x 109/L 
without platelet transfusion support for 7 days following the conditioning 
regimen associated nadir. 
 
Additional Secondary Endpoint: Time to engraftment defined as the time to 
neutrophils and platelets engraftment, whichever comes later. 
 
Additional Secondary Endpoint: Graft durability at 60 days post-
transplantation 
 
Additional Secondary Endpoint: Graft durability at 100 days post-
transplantation. 
 
Economic endpoint: The resource utilization until engraftment, 100 days 
after transplantation, multiplied with per country unit costs to obtain an 
average cost per patient per treatment arm. 
 
Exploratory Endpoint: Change from Baseline in peripheral blood CD34+ 
cell concentrations on apheresis Day 1 or Day 1 and 2, if applicable, after 
BL-8040/placebo single administration. 
 
Exploratory Endpoint: Mobilization of Multiple Myeloma cells in the 
apheresis product. 
 
Exploratory endpoint: To descriptively compare the CD34+ cells collected 
per kg of actual body weight (ABW) used in this study to the theoretical 
amount of CD34+ cells collected based on ideal body weight (IBW) 
The results and conclusions obtained from the integrative assessment of these 
efficacy endpoints, as well as accumulated safety data up to these cut-off dates, 
will be summarized in a Clinical Study Report (CSR) in support of regulatory 
approval and local market access of BL-8040 + G-CSF for the treatment of 
Multiple Myeloma. 

 
 
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Statistical 
Methodology  
 
BioLineRx believes that unblinding the study following the day that the last 
randomized subject completes the Core Study Termination Visit, which will 
occur at his/her Day 100 following transplantation, will not compromise study 
integrity and blinding and thus will not be associated with any bias for the 
subsequent sequence of the planned analyses due to the following reasons: 
 
Study recruitment, randomization and administration of study IP will 
already be completed at this study stage. 
 
Long-term graft durability endpoints are based on objective measures and 
therefore are not likely to be influenced from treatment allocation. 
 
The individual subject treatment assignment and data listings will only be 
shared with the Sponsor’s dedicated taskforce and with regulatory 
authorities.  
 
The publicly disseminated information will be on a by “group basis”.  
 
The observed summary statistics of efficacy outcomes will not allow 
determining individual subject assignment.  
 
The observed summary statistics of adverse events will not allow 
determining individual subject assignment. 
 
The third set of study accumulated data will be made available for statistical 
analyses of the long-term graft durability endpoints, as well as the longer-term 
safety data, on the day the last randomized subject completes Visit 16, which 
will occur at 12 months following transplantation. At that time, the study 
database will be locked again and a formal statistical analysis of the following 
endpoints will be conducted: 
 
Additional Secondary Endpoint: Graft durability at 6 months post 
transplantation. 
 
Additional Secondary Endpoint: Graft durability at 12 months post 
transplantation. 
 
Economic endpoint: The resource utilization until engraftment, 100 days 
post transplantation, multiplied with per country unit costs to obtain an 
average cost per patient per treatment arm. 
 
Exploratory Endpoint: Proportion of subjects with graft failure post-
transplantation. 
The results and conclusions obtained from the integrative assessment of these 
secondary efficacy endpoints, as well as accumulated safety data up to this cut-
off date, will be summarized in supplement to the CSR in further support of 
regulatory approval of BL-8040 + G-CSF for the treatment of Multiple 
Myeloma. 

 
 
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Statistical 
Methodology  
 
The last set of study accumulated data will be made available for statistical 
analyses of the long-term exploratory endpoints at 5 years following the 
randomization of the last study subject. At that time, the entire study will be 
terminated, the study database will be locked again, and a formal statistical 
analysis of the following endpoints will be conducted: 
 
Exploratory Endpoint: Overall Survival (OS) during the period of up to 5 
years. 
 
Exploratory Endpoint: Relapse-Free Survival (RFS) during the period of up 
to 5 years. 
 
Economic endpoint: The resource utilization until engraftment, 100 days 
post-transplantation, multiplied with per country unit costs to obtain an 
average cost per patient per treatment arm. Although no specific resource 
will be collected after day 100 post-transplantation, clinical endpoints per 
arm can be combined with unit costs to allow an economic evaluation. 
The results and conclusions obtained from the integrative assessment of these 
exploratory efficacy endpoints will be summarized in an additional supplement 
to the CSR in further support of the regulatory approval of BL-8040 + G-CSF 
for the treatment of Multiple Myeloma. 
Interim Analyses: 
An interim analysis for the primary endpoint only will be conducted for potential 
early termination of new subject recruitment into the study as described above. 
Statistical Analysis Plan (SAP): 
A more detailed SAP will be developed while the study is blinded, prior to the 
conduct of the predefined interim analysis. 
 
 

 
 
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GLOSSARY 
Abbreviation/Term Definition 
ABW 
Actual Body Weight 
ADA 
Anti-drug antibody 
ADL 
Activities of Daily Living 
AE 
Adverse event 
ALP 
Alkaline Phosphatase 
ALT (SGPT) 
Alanine transaminase (serum glutamate pyruvic transaminase) 
ANC 
Absolute neutrophil count 
aPTT 
Activated Partial Thromboplastin Time 
Ara-C 
Arabinofuranosyl Cytidine / Cytarabine / Cytosine Arabinoside 
AST (SGOT) 
Aspartate transaminase (serum glutamic oxaloacetic transaminase) 
AUC 
Area under the curve 
Auto-HCT 
Autologous Hematopoietic Cells Transplantation 
β-HCG 
Beta human chorionic gonadotropin 
BM 
Bone Marrow 
BA/BE 
Bioavailability / Bioequivalence 
BUN 
Blood urea nitrogen 
CABG 
Coronary Artery Bypass Grafting  
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CIBMTR 
Center for International Blood and Marrow Transplant Research 
Cmax 
Maximum plasma concentration 
cGMP 
Current Good Manufacturing Practice 
CNS 
Central nervous system 
CR 
Complete Response 
CrCl 
Creatinine Clearance 
CRF 
Case report form 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CXCL12 
C-X-C motif chemokine ligand 12 
CXCR4 
CXC Chemokine Receptor Type 4 
DFS 
disease free survival  
DNA 
deoxyribonucleic acid 
DMC 
Data Monitoring Committee 
ECG (or EKG) 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FACS 
Fluorescence-activated cell sorting 
FDA 
Food and Drug Administration 
FLC 
Free Light Chains 
FSH 
Follicle Stimulating Hormone 
GCP 
Good Clinical Practice 

 
 
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Abbreviation/Term Definition 
G-CSF 
Granulocyte Colony-Stimulating Factor 
GFR 
Glomerular Filtration Rate 
HBsAg 
Hepatitis B Surface Antigen 
HCs 
Hematopoietic Cells 
HCT 
Hematopoietic Cells Transplantation 
HCV 
Hepatitis C Virus 
Hep C Ab 
Hepatitis C Antibody 
HGB 
Hemoglobin 
HIV 
Human Immunodeficiency Virus 
HLT 
High Level Term  
HSC 
Hematopoietic Stem Cell 
HSPC 
Hematopoietic Stem and Progenitor Cell 
IB 
Investigator Brochure 
IBW 
Ideal Body Weight 
ICD 
Implantable Cardiac Defibrillator 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
INN 
International Non-proprietary Name 
INR 
International Normalized Ratio (for blood coagulation tests) 
IP 
Investigational Product  
IRB 
Institutional Review Board 
ITT 
Intention-to-treat 
IUD 
Intrauterine Device 
IUS 
Intrauterine Hormone-Releasing System 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
KRD 
Carfilzomib, lenalidomide, and dexamethasone 
LDH 
Lactate dehydrogenase 
MCH 
Mean Cell Hemoglobin 
MCHC 
Mean Cell Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intention-to-Treat Analysis 
MM 
Multiple myeloma 
MoA 
Mechanism of Action 
NCI 
National Cancer Institute 
OS 
Overall survival 
P1P2 
Study Part 1 and Part 2 Analysis Set 
PB 
Peripheral blood 
PCS 
Potentially Clinically Significant 
PD 
Pharmacodynamics 
PE 
Physical Exam 

 
 
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Abbreviation/Term Definition 
PI 
Principal investigator 
PK 
Pharmacokinetics 
POA 
Power of Attorney 
PP 
Per Protocol 
PR 
Partial Response 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
QA 
Quality Assurance 
RBC 
Red Blood Cell 
RFS 
Relapse free survival 
RNA 
Ribonucleic Acid 
RR 
Response rate 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SCR 
Stringent complete response 
SE 
Standard Error 
SOC 
System Organ Class 
SoC 
Standard of care  
SOP 
Standard Operation Procedures 
SPEP 
Serum protein electrophoresis 
ST 
Safety Analysis Set 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
T-ALL 
T-cell Acute Lymphoblastic Leukemia 
TBI 
Total Body Irradiation 
TEAE 
Treatment Emergent Adverse Event 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
US 
Ultrasound 
VGPR 
Very Good Partial Response 
VP 
Vice President 
VRD 
Bortezomib, lenalidomide, and dexamethasone 
WBC 
White blood cell (count) 
WHO 
World Health Organization 
λz 
Elimination rate constant 
 
 
 

 
 
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1. 
INTRODUCTION 
1.1 
THERAPEUTIC INDICATION 
Multiple myeloma (MM) is a condition in which there is a proliferation of malignant plasma 
cells derived from a single clone in the bone marrow. MM is the second most common 
hematologic malignancy1–3 and accounts for approximately 13% of all hematologic 
malignancies. The median age of patients at the time of diagnosis is approximately 65 years4. 
Common clinical features of MM are bone pain and pathologic fractures secondary to lytic 
lesions, renal failure, fatigue secondary to anemia and recurrent infections5. 
In the past, with conventional chemotherapy (melphalan and prednisone (MP)), the prognosis 
of MM was a median overall survival of 24 to 30 months. In the 1980s, high-dose 
chemotherapy and stem-cell rescue therapy via autologous hematopoietic cell transplantation 
(auto-HCT) was introduced, and randomized trials since then have demonstrated a survival 
advantage for this modality compared with conventional chemotherapy. The introduction of 
thalidomide represented a major milestone in the treatment of myeloma, and the subsequent 
availability of its analogs lenalidomide and pomalidomide, and proteasome inhibitors such as 
bortezomib and carfilzomib, have expanded therapeutic options further. Currently, median 
survival data exceed 45 to 60 months with this novel therapy6–9. 
Auto-HCT in MM has been shown to improve event-free survival and overall survival (OS) 
compared to conventional chemotherapy alone in previously untreated patients with standard-
risk MM10–12. However, the effectiveness of auto-HCT relies, in part, upon the ability to collect 
an adequate amount of hematopoietic cells (HCs), typically obtained from peripheral blood 
(PB). In order to perform an auto-HCT, a minimum of ≥2 x 106 CD34+ cells/kg are necessary, 
while transplants of ≥5-6 x 106 CD34+ cells/kg are associated with longer disease-free survival 
(DFS) and OS compared to lower transplant doses13–16. Despite the use of G-CSF to mobilize 
HCs to the PB and after multiple days of apheresis, ~10-30% of patients remain unable to 
produce an adequate number of cells for auto-HCT17–19.  Additionally, multiple apheresis days 
increase healthcare costs and account for additional logistical burden to both patients and the 
healthcare system. More recently, small molecules aimed at increasing circulating CD34+ cells 
have been shown to increase rates of successful collection with shorter collection times20.  
1.2 
INVESTIGATIONAL THERAPY 
1.2.1 BL-8040 
BL-8040 (formerly known as BKT140 and developed by Biokine Therapeutics Ltd.), is a novel 
selective inhibitor of the CXCR4 chemokine receptor. It is an investigational drug for several 
indications, including, among others: 
• The mobilization of hematopoietic stem cells (HSC) for autologous and/or allogeneic 
transplantations in subjects undergoing PB stem cell transplantation. 
• The treatment of patients with hematologic malignancies or pre-malignant conditions. 
• The treatment of patients with solid tumors. 
• The treatment of BM failure diseases. 
BL-8040 is a 14-residue, cyclic, synthetic peptide capped with an aromatic ring. BL-8040 binds 
and inhibits the CXCR4 chemokine receptor with high affinity (IC50 0.54 - 4.5 nM). BL-8040 
was shown in-vitro and in-vivo to be a specific antagonist of CXCR4 and to have a slow 

 
 
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dissociation rate from the receptor. In in-vivo animal studies, as well as in clinical studies, BL-
8040 has demonstrated accelerated mobilization of adult white blood cells (WBCs, neutrophils, 
monocytes and lymphocytes), normal stem-cells and leukemic blasts from the BM to the PB 
(see 1.2.1.1). 
In-vitro and in-vivo nonclinical studies have shown that, in addition to its activity as a 
mobilizer of hematopoietic cells, BL-8040 exhibits a CXCR4-dependent preferential anti-tumor 
effect against malignant cells. In-vivo preclinical studies have also shown that multiple doses of 
BL-8040 have led to a marked increase in the number of hematopoietic progenitor cells and 
hematopoietic stem cells (HSCs) in the BM and PB of mice. BL-8040 also promoted increased 
megakaryopoiesis in the BM, leading to increased platelet production with a prolonged effect 
in-vivo21–23. 
Detailed information on BL-8040 extensive nonclinical program is presented in the 
Investigator’s brochure (IB). 
1.2.1.1 Nonclinical Efficacy 
The interaction between CXCL12 and its receptor, CXCR4, is critically involved in the 
retention of HSPCs (Hematopoietic Stem and Progenitor Cells) and WBCs in the BM. 
Blocking of CXCR4 may result in the mobilization of these cells to the periphery, as 
demonstrated in nonclinical studies. The uptake dynamics found in-vitro were corroborated by 
in-vivo studies in mice, where a dose-dependent mobilization of WBCs (peak at 0.5 hr) to the 
peripheral blood was observed as a result of a single injection of BL-8040.  BL-8040 induced 
rapid (0.5-2 hrs), dose-dependent and transient mobilization of WBCs, including monocytes, B 
cells, T cells, progenitors and stem cells in mice treated with BL-8040 as a single agent21. The 
effect was seen in mice at a dose range of 2.5-10 mg/kg, equivalent to the human dose of 0.2-
0.83 mg/kg, in respectively. 
Single injection of BL-8040 to mice at 6 mg/kg (human equivalent dose of 0.49 mg/kg) 
induced the mobilization of HSC progenitor cells at 30 minutes and reached a peak 1 to 2 hours 
post‐injection with approximately 10‐fold increases over control (p < 0.01). Higher doses of 
BL-8040 alone or in combination with G‐CSF were used to induce the mobilization of 
progenitors and long-term repopulating stem cells with better engraftment abilities (report 140‐
RD‐R‐04). Single injection of BL-8040 to mice at a higher dose (12 mg/kg, human equivalent 
dose of 0.99 mg/kg) showed a robust, prolonged and dose‐dependent increase in the number of 
HSCs mobilized to the blood. A peak in mobilization occurred at 4 hrs post‐injection, with 
approximately 18.6-fold increase from the control), which slowly decreased at 8 hrs post 
dosing. The effect was still evident at 24 hrs post‐injection showing a 3-fold increase from the 
control. 
1.2.1.2 Clinical Experience 
These nonclinical results were further supported by findings from two clinical studies: Clinical 
study BKTSC001 (NCT01010880) and clinical study BL-8040.02 (NCT02073019). In study 
BKTSC001, which was conducted in MM patients, a single administration of BL-8040, when 
combined with a standard G-CSF mobilization regimen, facilitated the rapid and robust 
mobilization of stem cells and WBCs in a BL-8040 dose-dependent manner. At the top two 
dose levels tested (0.3 and 0.9 mg/kg; equivalent to 0.24 and 0.73 mg/kg free base peptide on 
dry basis), there was an approximately 4-fold increase in peripheral WBC counts and 10 to 20-
fold increase (0.3 and 0.9 mg/kg, respectively) in peripheral CD34+ cells (stem cells).  

 
 
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In study BL-8040.02 a single administration of BL-8040, as a single agent, at doses ranging 
between 0.5-1 mg/kg (free base peptide on dry basis) to healthy volunteers resulted in rapid and 
robust mobilization of stem cells and WBCs in a BL-8040 dose-dependent manner. After 
administration of the first dose of BL-8040, CD34+ counts increased with time, reaching 
maximal levels between 9 and 11 hours. The maximal counts increased with doses averaging 
9.31, 38.2, 43.7 and 45.5 CD34+/μL for placebo, 0.5, 0.75, and 1 mg/kg groups, respectively. 
By 24 hours, CD34+ levels had slightly declined, but were still 5 to 7-fold higher than 
Baseline. Upon administration of the second dose, an additional increase in CD34+ was 
observed, with maximal counts obtained between 4 and 7 hours after dosing. The CD34+ 
counts declined thereafter, reaching Baseline levels approximately 48 hours after the second 
dose, suggesting a long PD half-life. On both study days, the PD parameters increased with 
dose and were higher after the second dose relative to the first dose. After the first dose, a 5 to 
10-fold increase from baseline was observed in CD34+ counts. 
BL-8040-Related Adverse Events 
Full details of the adverse events (AE) seen in each clinical trial are presented in the IB. 
Based on the clinical experience to date, the following adverse events may be anticipated 
following administration of BL-8040: Injection-site reactions (including pain, erythema, 
pruritus and inflammation) and systemic reactions (hives, pruritus (not at the injection site), 
flushing, hot flushes, chills, rash, urticaria and hypotension). These two groups of reactions are 
well managed with pre-medication and/or post event treatment using steroids and 
antihistamines. Other isolated AEs reported to date include paresthesia, musculoskeletal pain, 
headache, constipation, diarrhea, abdominal pain, fatigue, nausea, vomiting, increased liver 
transaminases, increased alkaline phosphatase, dyspnea and hypokalemia. Bone marrow 
suppression resulting in decreased monocyte count, neutropenia and thrombocytopenia (which 
in turn may cause petechiae), as well as ataxia and alopecia are expected outcomes of treatment 
with high dose Ara-C, as administered in study BL-8040.01. BioLineRx has therefore not listed 
them as anticipated side effects of BL-8040.   
Leukocytosis and high and low peripheral blast counts are an expected pharmacodynamic 
effect of treatment with BL-8040. To date, leukocytosis has been reported in only one patient 
treated with Nelarabine and BL-8040 for T-ALL.  
Most of the AEs observed were transient and mild to moderate in severity. Clinically-
appropriate measures should be considered in case of BL-8040-related local reactions at the 
injection site (e.g., local treatments with steroids and or antihistamines) and systemic reactions 
(e.g. systemic antihistamines and steroids) with preventive treatment before subsequent doses. 
Potential Safety Considerations Based on the BL-8040 MoA 
Leukostasis is an important medical event that should be considered based on the 
pharmacodynamic properties of BL-8040. The promotion of WBCs and HSCs mobilization 
from the Bone Marrow (BM) may result in leukostasis, the presence of very high WBC counts 
in the peripheral circulation causing small vessel occlusion with a variety of clinical sequelae 
including visual symptoms, dyspnea and hypoxia. To date, leukostasis has been reported in 
only one patient treated with nelarabine and BL-8040 for T-ALL. 
1.2.2 G-CSF (Filgrastim) 
Filgrastim is a 175 amino-acid protein manufactured by recombinant DNA technology. It is 
produced by Escherichia coli bacteria into which the human granulocyte colony stimulating 

 
 
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factor gene has been inserted. Filgrastim is unglycosylated and contains an N-terminal 
methionine necessary for expression in E. coli. 
Colony-stimulating factors are glycoproteins that act on hematopoietic cells by binding to 
specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and 
some end-cell functional activation.  
Endogenous G-CSF is a lineage-specific colony-stimulating factor which is produced by 
monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils 
within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and 
selected end-cell functional activation (including enhanced phagocytic ability‚ priming of the 
cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the 
increased expression of some functions associated with cell surface antigens). G-CSF is not 
species-specific and has been shown to have minimal direct in-vivo or in-vitro effects on the 
production of hematopoietic cell types other than the neutrophil lineage. 
Absorption and clearance of filgrastim follows first-order pharmacokinetic modeling without 
apparent concentration dependence. A positive linear correlation occurred between the 
parenteral dose and both the serum concentration and area-under-the-concentration-time 
curves. Continuous IV infusion of 20 mcg/kg of filgrastim over 24 hours resulted in mean and 
median serum concentrations of approximately 48 and 56 ng/mL‚ respectively. Subcutaneous 
(SC) administration of 3.45 mcg/kg and 11.5 mcg/kg resulted in maximum serum 
concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. The volume of distribution 
averaged 150 mL/kg in both normal subjects and cancer patients. The elimination half-life‚ in 
both normal subjects and cancer patients‚ was approximately 3.5 hours. Clearance rates of 
filgrastim were approximately 0.5 to 0.7 mL/minute/kg. Single parenteral doses or daily IV 
doses‚ over a 14-day period‚ resulted in comparable half-lives. The half-lives were similar for 
IV administration (231 minutes‚ following doses of 34.5 mcg/kg) and for SC administration 
(210 minutes‚ following filgrastim doses of 3.45 mcg/kg). Continuous 24-hour IV infusions of 
20 mcg/kg over an 11- to 20-day period produced steady-state serum concentrations of 
filgrastim with no evidence of drug accumulation over the time period investigated. 
1.2.3 Transplantation 
The following adverse events are related to hematopoietic stem cell transplantation and can be 
anticipated following myeloablation and further Auto-HCT. 
• Alopecia 
• Anemia 
• Creatinine elevations 
• Diarrhea 
• Edema 
• Fatigue 
• Febrile neutropenia 
• Gastritis 
• Hematuria 
• Hemorrhage 
• Hypotension 
• Hypoxemia 
• Incontinence 
• Infection / Sepsis 

 
 
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• Infertility 
• Insomnia 
• Liver function test alterations 
• Mental status changes 
• Mood alterations 
• Mucositis 
• Nausea / Vomiting 
• Neutropenia 
• Pain 
• Pleural effusion 
• Pneumonitis 
• Thrombocytopenia 
• Veno-occlusive disease 
 
1.3 
STUDY RATIONALE 
Autologous hematopoietic cell transplantation (auto-HCT) in multiple myeloma (MM) has 
been shown to improve overall survival (OS) compared to conventional chemotherapy10–12. 
However, the effectiveness of auto-HCT relies, in part, upon the ability to collect an adequate 
amount of hematopoietic cells (HCs), typically obtained from peripheral blood (PB). In order 
to perform an auto-HCT, a minimum of ≥2 x 106 CD34+ cells/kg are necessary, while 
transplants of ≥5-6 x 106 CD34+ cells/kg are associated with longer disease-free survival 
(DFS) and OS compared to lower transplant doses13–16. Despite the use of G-CSF to mobilize 
HCs to the PB and after multiple days of apheresis, ~10-30% of patients remain unable to 
produce an adequate number of cells for auto-HCT17–19. Additionally, multiple apheresis days 
increase healthcare costs and account for additional logistical burden to both patients and the 
healthcare system.  
In-vitro studies demonstrated that BL-8040 binds and inhibits the CXCR4 chemokine 
receptor with high affinity. It was shown in-vitro and in-vivo to be a specific antagonist of 
CXCR4 and to have long receptor occupancy (>48 hrs). In in-vivo animal studies, as well as 
in clinical study BKTSC001, BL-8040 demonstrated accelerated mobilization of adult WBCs 
(neutrophils, monocytes, lymphocytes) and HSCs22. 
Despite the use of G-CSF, there remains a significant number of patients who are unable to 
collect both the minimum number and the optimal number of CD34+ cells/kg prior to auto-
HCT. Based on the previous success of BL-8040 to mobilize hematopoietic cells (studies 
BKTSC001 and BL-8040.02), we propose that the combination of G-CSF and BL-8040 will 
allow larger proportions of the patient population to collect the minimum and optimal 
numbers of CD34+ cells/kg, in fewer apheresis sessions.  
BL-8040 will first be used in an open label, dose-evaluating, lead-in protocol, followed by a 
randomized, placebo-controlled 2-arm protocol with the primary endpoint assessing the 
proportion of patients who collect ≥6 x 106 CD34+ cells/kg in 2 apheresis sessions. 
Secondary endpoints will assess the proportion of patients who collect ≥2 x 106 CD34+ and 
cells/kg or ≥6 x 106 CD34+ cells/kg in a single apheresis session. However, any patient not 
achieving the collecting goal after 2 apheresis sessions, will be allowed to continue apheresis 
with a second dose of BL-8040/placebo in order to capture a more “difficult-mobilizer” 

 
 
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cohort of patients. Additional secondary endpoints will assess the time to engraftment and 
graft durability at different time-points. 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 
STUDY OBJECTIVES 
2.1.1 Primary Objective 
The primary objective of the study is to demonstrate the superiority of one dose of BL-8040 
+ G-CSF over placebo + G-CSF to mobilize ≥6.0 x 106 CD34+ cells/kg in up to 2 apheresis 
sessions in preparation for autologous hematopoietic cell transplantation (auto-HCT) in MM 
subjects. 
2.1.2 Secondary Objectives 
The secondary objectives of the study are: 
 To demonstrate the superiority of one dose of BL-8040 + G-CSF over placebo + G-
CSF to mobilize ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session in preparation for 
auto-HCT in MM subjects. 
 To demonstrate the superiority of one dose of BL-8040 + G-CSF over placebo + G-
CSF to mobilize ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session in preparation for 
auto-HCT in MM subjects. 
 To descriptively assess the comparability between the effects of BL-8040 + G-CSF and 
placebo + G-CSF in time to neutrophil engraftment, platelet engraftment and the later 
of the two. 
 To descriptively assess the comparability between the effects of BL-8040 + G-CSF and 
placebo + G-CSF on graft durability at 60 days, 100 days, as well as 6 and 12 months 
post-transplantation. 
 To demonstrate that the use of (one or two doses of) BL-8040 + G-CSF over placebo + 
G-CSF results in a reduction in resource use and cost savings 
2.1.3 Exploratory Objectives 
The exploratory objectives of the study are: 
 To demonstrate the superiority of BL-8040 + G-CSF over placebo + G-CSF in 
increasing CD34+ cell concentration in the peripheral blood on apheresis Day 1 or Day 
1 and 2, if applicable. 
 To descriptively assess the comparability between the effects of BL-8040 + G-CSF and 
placebo + G-CSF in graft failure post-transplantation.  
 To descriptively assess the comparability between the effects of BL-8040 + G-CSF and 
placebo + G-CSF in overall survival with up to 5 years follow-up. 
 To descriptively assess the comparability between the effects of BL-8040 + G-CSF and 
placebo + G-CSF in relapse free survival with up to 5 years follow-up. 
 To descriptively assess the comparability between the effects of BL-8040 + G-CSF and 
placebo + G-CSF in the mobilization of Multiple Myeloma cells in the apheresis 
product. 

 
 
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 To descriptively compare the CD34+ cells collected per kg of actual body weight 
(ABW) used in this study to the theoretical amount of CD34+ cells collected based 
on ideal body weight (IBW) 
2.1.4 Safety and Tolerability Objectives  
To demonstrate that the combination of BL-8040 + G-CSF is safe and tolerable as compared 
to Placebo + G-CSF. 
2.1.5 Pharmacokinetic Endpoint 
 BL-8040 exposure as measured by Cmax and AUC (See Section 5.6). 
 Effect of covariates such as body weight and age on BL-8040 exposure. 
 Exposure-response analysis, if warranted. 
2.1.6 Pharmacoeconomic Endpoints 
The resource utilization up until engraftment, 100 days after transplantation, multiplied with 
per country unit costs to obtain an average cost per patient per treatment arm. 
2.2 
STUDY ENDPOINTS/OUTCOMES 
2.2.1 Efficacy Endpoints 
2.2.1.1 Primary Endpoint 
Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions 
in preparation for auto-HCT after G-CSF + single administration of BL-8040 or placebo + G-
CSF. 
2.2.1.2 Secondary Endpoints 
 Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session  
 Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session  
2.2.1.3 Additional Secondary Efficacy Endpoints 
The comparability between the effects of BL-8040 + G-CSF and placebo + G-CSF the below 
endpoints will be assessed in a descriptive manner: 
 Time from transplantation to neutrophil engraftment, defined as ANC ≥0.5 x 109/L for 
3 consecutive days or ≥1.0 x 109/L for 1 day following the conditioning regimen 
associated nadir.  
 Time from transplantation to platelet engraftment, defined as the first of 3 consecutive 
measurements of platelet count ≥20 x 109/L without platelet transfusion support for 7 
days following the conditioning regimen associated nadir. 
 Time from transplantation to engraftment, defined as the time to neutrophils and 
platelets engraftment, whichever comes later. 
 Graft durability at 60 days post-transplantation. Visit 12 scheduling may be within ±14 
days of Day 60, provided that the visit takes place before starting maintenance therapy.  
 Graft durability at 100 days post-transplantation.  
 Graft durability at 6 months post-transplantation. 

 
 
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 Graft durability at 12 months post-transplantation. 
2.2.1.4 Exploratory Endpoints 
 Change from Baseline in peripheral blood CD34+ cell concentration on apheresis Day 
1 or Day 1 and Day 2, if applicable, after BL-8040/placebo single administration. 
 Incidence of graft failure post-transplant.  
 Overall survival with up to 5 years follow-up. 
 Relapse free survival with up to 5 years follow-up. 
 Mobilization of Multiple Myeloma cells assessed in the apheresis product (only from 
Part 2). 
 CD34+ cells collected per kg of actual body weight (ABW) compared to theoretical 
amount of cells collected based on ideal body weight (IBW). 
2.2.2 Exploratory Biomarkers 
Immunophenotyping of lymphocyte subsets in apheresis product. 
2.2.3 Safety and Tolerability Outcomes 
Incidence of AEs, defined and graded according to the NCI-issued Common Terminology 
Criteria for Adverse Events (CTCAE). 
Incidence of early discontinuation and early discontinuation due to adverse events. 
2.2.4 Pharmacokinetic Endpoint 
 BL-8040 exposure as measured by Cmax and AUC (See Section 5.6). 
 Effect of covariates such as body weight and age on BL-8040 exposure. 
 Exposure-response analysis, if warranted. 
2.2.5 Pharmacoeconomic Endpoints 
The resource utilization up until engraftment, 100 days after transplantation, multiplied with 
per country unit costs to obtain an average cost per patient per treatment arm   
3. 
STUDY DESIGN 
A multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate 
the effect of BL-8040 in combination with G-CSF on mobilizing CD34+ cells. This Phase III 
study will be composed of two sequential parts, as described hereafter:  
3.1 
PART 1 
This lead-in period is designed to ascertain the dose of BL-8040 and will enroll a total of up 
to 30 subjects to an open labeled treatment to assess the efficacy, safety and tolerability of the 
treatment with G-CSF ~10 µg/kg/day (and maximum of 15 µg/kg)  and BL-8040 1.25 mg/kg, 
per study protocol, to achieve the goal collection of ≥ 6 x 106 CD34+ cells/kg.  

 
 
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An independent data monitoring committee (DMC) will then assess the accumulated data of 
this lead-in period and recommend whether to continue to Part 2 of the study with BL-8040 
1.25 mg/kg. The review of the accumulated data of Part 1 will be conducted in 3 sequential 
steps: 
 Initially, the accumulated data of 10 subjects will be summarized and reviewed by the 
DMC, which may recommend that Sponsor either study an additional cohort of 10 
subjects, lower the dose, discontinue the study or continue to Part 2 of the study. 
 Similarly, after reviewing the accumulated data of a total of 20 subjects, the DMC may 
recommend that the Sponsor either study an additional cohort of 10 subjects, lower the 
dose, discontinue the study or continue to Part 2 of the study. 
 Lastly, after reviewing the accumulated data of a total of 30 subjects, the DMC will 
make recommendations regarding study continuation.  
 
The below quantitative decision rules will be taken into consideration by the DMC:  
 The primary efficacy endpoint of the study is the proportion (%) of subjects mobilizing 
≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions in preparation for auto-HCT 
after G-CSF + single administration of BL-8040 or placebo + G-CSF. 
 After the review of the accumulated data of 10 subjects, enroll an additional 10 subjects 
if the number of subjects meeting primary efficacy endpoint is less than or equal to 6. 
 After the review of the accumulated data of 20 subjects, enroll an additional 10 subjects 
if the number of subjects meeting primary efficacy endpoint is less than or equal to 12. 
 After the review of the accumulated data of 30 subjects early terminate the study if the 
number of subjects meeting primary endpoint is less than or equal to 16. 
Furthermore, the DMC will have the freedom to employ more conservative decision rules 
based on integrative risks and benefits assessments of the accumulated information of the 
study at each decision point.   
All subjects treated during Part 1 will continued to be followed concomitantly to the conduct 
of Part 2 and according to the same visit schedule until study termination. 
3.2 
PART 2  
Following the successful completion of Part 1, a total of 177 subjects will be randomized into 
Part 2 of the study, which will employ a randomized, double-blinded, placebo-controlled 
design to assess the efficacy, safety and tolerability of BL-8040 + G-CSF as compared to 
Placebo + G-CSF. 
One interim analysis for potential early termination of new subject recruitment into the study 
will be conducted at the time when a total of 65% of the planned sample size will be 
randomized and have completed the stem cell mobilization procedure. 
3.3 
BOTH PARTS 
The procedure is presented in graphic form in Figure 1. 
Each part of the study will consist of the following study periods:  
Screening: Within 28 days prior to starting mobilization regimen (Day 1) 

 
 
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Mobilization and Apheresis: From Day 1 to the day before myeloablative chemotherapy 
(Visit 9); Goal: 3 weeks, maximum: 5 weeks. 
Chemotherapy and Transplantation: From first day of myeloablation (Visit 9) to the first day 
of platelet and neutrophil engraftment (whichever comes later) after transplantation; expected 
within 2-3 weeks, maximum not defined. 
Short-Term Graft Durability: From the first day after engraftment to Day 60 and 100 after 
transplantation. 
Long-Term Graft Durability: From 100 days after transplantation until 12 months after 
transplantation. 
Relapse free survival (RFS): From 12 months after transplantation until a maximal period of 
5 years from last patient randomization day. 
Overall Survival (OS): From 12 months after transplantation until a maximal period of 5 
years from last patient randomization day. 
Subjects to be enrolled in Part 2 will be randomized in a 2:1 ratio to receive either BL-8040 
or placebo, respectively, plus G-CSF. Randomization will be stratified by remission status 
(Complete remission (CR) vs. Partial Remission (PR))a and baseline platelet count (<200 x 
109/L or ≥200 x 109/L). The apheresis product will be processed and stored according to local 
practice guidelines at each study center. 
Subjects will undergo mobilization with G-CSF ~10 µg/kg (and maximum of 15 µg/kg) 
subcutaneously (SC) daily in the morning for up to 8 days. Beginning on the evening of Day 
4, subjects will receive either a single injection of BL-8040 or placebo SC. In the morning of 
Day 5, a 5th dose of G-CSF will be administered prior to apheresis. Subjects will then 
undergo first apheresis per institutional protocol (4 blood volumes ±10% /apheresis). In the 
event that the subject does not reach the collection goal for mobilization (≥6.0 x 106 CD34+ 
cells/kg), on Day 6, a 6th dose of G-CSF will be administered prior to the second apheresis 
session in an effort to reach a total of ≥6 x 106 CD34+ cells/kg. 
If the subject does not reach the collection goal for mobilization (≥6.0 x 106 CD34+ cells/kg), 
a second dose of BL-8040/placebo will be administered in the evening of Day 6 and a 7th 
dose of G-CSF will be administered in the morning of Day 7 prior to the third apheresis 
session. If the subject still does not reach the collection goal for mobilization (≥6.0 x 106 
CD34+ cells/kg), a fourth and final apheresis will be performed on Day 8 with an 8th dose of 
G-CSF administered prior to the apheresis, in an effort to collect a total of ≥6 x 106 CD34+ 
cells/kg, but at least ≥ 2 x 106 CD34+ cells/kg from the combined collections. Subjects who 
fail to collect the minimum required CD34+ cells/kg will be subsequently managed per 
investigator preference in accordance with standard of care guidelines. They may reattempt 
mobilization per standard of care after no less than 7 day “rest/wash-out” period (7 days from 
the last dose of BL-8040/placebo). Subjects who fail to collect enough CD34+ cells in four 
apheresis sessions will continue to be followed according to the protocol schedule of visits. 
The entire study, both Part 1 and Part 2 of the study, will be monitored by an independent 
DMC according to signed charter in line with regulatory guidelines (see Section 9.7). 
 
a The group of Partial Response (PR) will include PR and Very Good PR (VGPR) and the Complete Response (CR) group 
will include CR and Stringent CR (SCR). 

 
 
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Figure 1: Stem Cell Mobilization Procedure 
 
 
4. 
STUDY POPULATION 
4.1 
NUMBER OF SUBJECTS 
A total of up to 207 subjects will be enrolled into the study: 
• Part 1: Open-label Lead-in – will enroll up to 30 subjects. 
• Part 2: Randomized, Double-blinded – will enroll a total of 177 subjects. 
4.2 
INCLUSION CRITERIA 
1. Patients must be between the ages of 18 and 78 years. 
2. Patient must have a signed study informed consent prior to entering the study. 
3. Histologically confirmed MM prior to enrollment and randomization. 
4. At least 1 week (7 days) from last induction cycle of combination/multi-agent 
chemotherapy (e.g. KRD [carfilzomib, lenalidomide, dexamethasone] or VRD 
[bortezomib, lenalidomide, dexamethasone]) or  last single agent chemotherapy (e.g. 
lenalidomide, pomalidomide, bortezomib, dexamethasone, etc) prior to the first dose 
of G-CSF for mobilization. 
5. Eligible for Autologous Hematopoietic stem cell transplantation according to the 
Investigator’s discretion. 
6. The subjects should be in first or second CR (including CR and SCR) or PR 
(including PR and VGPR). 
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (see 
Appendix B). 

 
 
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8. Adequate organ function at screening as defined below: 
a. 
Hematology: 
• White blood cell-count more than 2.5 x 109/L  
• Absolute neutrophil count more than 1.5 x 109/L 
• Platelet count more than 100 x109/L 
b. Renal Function: 
• GFR ≥15 mL/min/1.732 calculated by MDRD equation 
c. 
Hepatic function: 
• ALT and/or AST ≤ 2.5 x ULN. 
• Total Bilirubin ≤ 2.0 x ULN unless the subject has Gilbert disease.  
d. Coagulation test: 
• INR or PT: ≤1.5xULN unless subject is receiving anticoagulant therapy, as 
long as PT or PTT is within therapeutic range of intended use of 
anticoagulants. 
• aPTT: ≤1.5xULN unless subject is receiving anticoagulant therapy, as long 
as PT or PTT is within therapeutic range of intended use of anticoagulants. 
9. Female subjects must be of non-childbearing potential or, if of childbearing 
potential, must have a negative serum pregnancy test at screening and negative 
urine/serum pregnancy test within 72 hours prior to G-CSF first administration.  
10. Women of childbearing potential must agree to use 2 methods of effective 
contraception: One barrier method (e.g. diaphragm, or condom or sponge, each of 
which are to be combined with a spermicide) and one hormonal method, unless she 
uses a highly effective method. Highly effective methods of contraception include: 
• Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation: oral, intravaginal, transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
oral, injectable, implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomised partner 
• Sexual abstinence. 
 

 
 
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These methods must be used prior to study entry and for the duration of study 
participation through 30 days after the last dose of study treatment. Non-childbearing 
potential is defined as (by other than medical reasons): 
• ≥45 years of age and has not had menses for over 2 years. 
• Amenorrheic for > 2 years without a hysterectomy and oophorectomy and a 
Follicle Stimulating Hormone (FSH) value in the postmenopausal range upon pre-
trial (screening) evaluation. 
• Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral 
tubal ligation at least 6 weeks prior to screening. Documented hysterectomy or 
oophorectomy must be confirmed with medical records of the actual procedure or 
confirmed by ultrasound. Tubal ligation must be confirmed with medical records 
of the actual procedure; otherwise the subject must be willing to use two adequate 
barrier methods throughout the study, starting with the Screening Visit, through 
30 days after the last dose of study drug. Information must be captured 
appropriately within the site's source documents. 
11. Male subjects must agree to use an adequate method of contraception starting with 
the first day of G-CSF treatment through 30 days after the last dose of study drug. 
4.3 
 EXCLUSION CRITERIA 
1. Previous history of autologous or allogeneic-HCT. 
2. Failed previous HSC collections or collection attempts. 
3. Taken any of the listed below concomitant medications, growth factors or stimulating 
agents within the designated washout period:  
a. Dexamethasone: 7 days 
b. Thalidomide: 7 days 
c. Lenalidomide: 7 days 
d. Pamolidomide: 7 days 
e. Bortezomib: 7 days 
f. Carfilzomib: 7 days 
g. G-CSF: 14 days 
h. GM-CSF or Neulasta®: 21 days 
i. Erythropoietin or erythrocyte stimulating agents: 30 days 
j. Eltrombopag, romiplostim or platelet stimulating agents: 30 days 
k. Carmustine (BCNU): 42 days/6 weeks 
l. Daratumumab: 28 days 
m. Ixazomib: 7 days  
4. Received >6 cycles lifetime exposure to thalidomide or lenalidomide.  
5. Received > 8 cycles of alkylating agent combinations. 
6. Received > 6 cycles of melphalan. 
7. Received prior treatment with radioimmunotherapy, (e.g. radionuclides, holmium). 
8. Received prior treatment with venetoclax. 

 
 
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9. Plans to receive maintenance treatment within 60 days post-transplantation (e.g. 
lenalidomide, bortezomib, pomalidomide, thalidomide, carfilzomib, etc.). 
10. Has received a live vaccine within 30 days of the planned start of G-CSF 
administration. Seasonal flu vaccines that do not contain live virus are permitted. 
11. Known active CNS metastases or carcinomatous meningitis. 
12. A history of allergic reactions attributed to compounds of similar chemical or biologic 
composition to BL-8040, G-CSF, or other agents used in the study. 
13. Has an active infection requiring systemic therapy or uncontrolled infection. 
14. Has a known additional malignancy that is progressing or requires active treatment.  
15. Has an underlying medical condition that would preclude study participation. 
16. Is currently participating and receiving study therapy or has participated in a study of 
an investigational agent and received study therapy or used an investigational device 
within 4 weeks of the first dose of treatment. 
17. O2 saturation < 92% (on room air). 
18. Personal history or family history of Long QT Syndrome or Torsade de Pointes. 
19. History of unexplained syncope, syncope from an uncorrected cardiac etiology, or 
family history of sudden cardiac death. 
20. Myocardial infarction, CABG, coronary or cerebral artery stenting and /or 
angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure 
within 3 months or greater than Angina Pectoris Class >2 or NYHA Heart Failure 
Class >2. 
21. ECG at Screening showing QTcF > 470 msec and/or PR > 280 msec. 
22. Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete 
Heart Block, unless the patient has an implanted pacemaker or implantable cardiac 
defibrillator (ICD) with backup pacing capabilities. 
23. Has a history or current evidence of any condition, therapy, or laboratory abnormality 
that might confound the results of the trial, interfere with the subject’s participation 
for the full duration of the trial, or is not in the best interest of the subject to 
participate, in the opinion of the treating Investigator. 
24. Has known psychiatric or substance abuse disorders that would interfere with 
cooperation with the requirements of the trial. 
25. Is pregnant or breast feeding or expecting to conceive or women of childbearing 
potential unless consent to use two contraceptive methods or highly effective 
contraception as detailed above, within the projected duration of the trial, starting with 
the Screening Visit through 30 days after the last dose of study drug.  
26. Has a known history of HIV (HIV 1/2 antibodies) 
27. Has known active Hepatitis B (e.g., Hepatitis B Surface Antigen [HBsAg] reactive) or 
Hepatitis C (e.g., Hepatitis C Virus [HCV] RNA [qualitative] is detected). 
28. Untreated or unsuccessfully treated Hepatitis B or C. 

 
 
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4.4 
SUBJECT IDENTIFICATION 
At screening, all subjects who signed informed consent will be identified by a subject number 
provided during the registration in IWRS system. The subject number will be used 
throughout the study.  
Subjects who fail the screening procedures may be re-screened. Re-screening should include 
all screening procedures listed in the protocol flow chart, including signature of a new 
consent form.  
Any subject who is re-screened will be assigned a new subject number and his/her previous 
subject number will be documented in CRF. 
4.5 
SCREENING FAILURES 
Subjects who fail to meet the entrance criteria at any stage during the screening period are 
defined as screen failures. All screen failures will be documented on the screening log 
including reason(s) for screen failure. The screening log will be kept in the Investigator's Site 
File. Screening failures should be registered as failures in the IWRS system and CRF. Reason 
for screening failure should be captured within CRF and the IWRS system. 
Screen failure subjects will not be enrolled to the study and will receive standard of care 
performed at the site.  
4.6 
REMOVAL, EARLY WITHDRAWAL OF SUBJECTS FROM THERAPY OR ASSESSMENT 
 Subjects are free to discontinue their participation in the study at any time and without 
prejudice to further treatment. The Investigator must withdraw any subject from the 
study if that subject requests to be withdrawn, or if it is determined that continuing in 
the study would result in a significant safety risk to the subject. In urgent cases, the 
investigator has the ability to unblind the trial treatment immediately. The IWRS 
system will notify all relevant persons of the unblinding event. 
 Subjects withdrawn from the study at any time will not be replaced.   
 Subject participation in this study may be discontinued due to the following reasons: 
• Subject withdrew consent  
• Request of the Sponsor  
• Request of the primary care physician or Investigator  
• Non-adherence to study requirements 
• Protocol violation 
• Adverse Event/Experience  
• Loss to follow-up/failure to return 
• Death 
• Pregnancy 
• Other  
4.7 
HANDLING OF WITHDRAWALS 
If a subject is withdrawn from the study, either at his or her request or at the Investigator’s 
discretion, or if requested by the Sponsor, primary care physician or regulatory agency, or 
fails to return, every effort should be made to determine the reason. This information will be 

 
 
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recorded on the subject’s case report form (CRF) at Visit 13 - Termination/Early Termination 
All subjects who withdraw from the study prematurely, regardless of cause, should undergo 
all procedures of the Early Termination Study Visit (see 5.2.7.4). It is vital to obtain follow-
up data for any subject withdrawn because of an AE. In any case, every effort must be made 
to undertake safety follow-up procedures. 
If a subject withdraws from the study, all procedures of early termination visit should be 
performed unless withdrawal occurs after Visit 13. 
Subjects will consent to be followed under the same protocol assessments in case of 
withdrawal, by signing the ICF.  
Any serious AE (SAE) must be reported to the Sponsor or Sponsor's designee by telephone, 
email or fax within 24 hours of becoming aware of the event and to the IRB/IEC according to 
local regulations (for SAE notification procedures, refer to 7.5).  
In the event of any AEs considered to be clinically significant by the Investigator, subjects 
will be followed up with appropriate medical management until the AE is resolved or 
stabilized, according to the Investigator’s clinical judgment. All follow-up information will 
be recorded in the subject's CRF until resolution/stabilization of the AE. Subsequent follow-
up will be documented in the subject's personal file. 
Patients who undergo apheresis on study with CD34+ cells collected, but who either fail to 
meet the collection goals or withdraw from the study for any of the aforementioned reasons, 
will continue to be followed as outlined above and under section 5.2.5.  
A patient who received G-CSF and discontinued before receiving first BL-8040 could 
potentially be rescreened assuming washout period from G-CSF is completed.  
4.8 
SPONSOR'S TERMINATION OF STUDY  
The Sponsor reserves the right to early discontinue the study at any time for any reason.  
Regulatory Authorities also have the right to terminate the study for any reason. 
5. 
STUDY PROCEDURES AND ASSESSMENTS 
The schedule of events for this study is shown in Appendix A.  No protocol-related 
procedures should be performed before the subject provides written informed consent. Study-
related events and activities including specific instructions, procedures, concomitant 
medications, dispensing of study medication, and descriptions of AEs should be recorded in 
the appropriate source documents and CRF.  
5.1 
SCREENING PERIOD (FROM THE TIME OF INFORMED CONSENT FORM (ICF) 
SIGNATURE UNTIL DAY 0 (BASELINE VISIT)) 
During the Screening Visit, the subject must be thoroughly informed about all aspects of the 
study, including scheduled study visits and activities, and must sign the informed consent 
form (ICF; see 9.3).  
Prior to any study activities/evaluation, the subject will be allocated a subject number using 
an Interactive Web Response System (IWRS), which will be used throughout the study, and 
assessed for eligibility criteria.  
 

 
 
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A window of up to 28 days is allowed for the screening period procedures. Urinary and blood 
laboratory assessments, as well as ECG, must be completed within 10 days (+2 days) before 
G-CSF administration, except blood serology, UPEP, SPEP, immunofixation and FLC. 
Potential subjects will be assessed for fulfillment of the entry requirements as detailed in the 
Inclusion and Exclusion criteria (see Sections 4.2 and 4.3). 
Screening period procedures: 
 ICF process 
 Inclusion/exclusion criteria review  
 Collect demographics and medical history 
 Review prior and concomitant medications 
 Complete physical examination 
 IWRS  
 Adverse Events (AEs) recording starting from ICF signature 
 12 lead electrocardiogram (ECG) 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature [°C] and room 
air SPO2) 
 Eastern Cooperative Oncology Group (ECOG) performance status 
 Coagulation Test: Prothrombin Time (PT)/International Normalized Ratio (INR) 
and Activated Partial Thromboplastin Time (aPTT)    
 Complete Blood Count (CBC) with differential 
 Blood chemistry 
 Serum pregnancy test for all female patients of childbearing potential 
 Blood Serology Assessment 
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation-24 hours 
urine collection is required  
 Serum Free Light Chain (FLC) 
 Urinalysis 
 Bone marrow biopsy – only for CR/sCR patients 
 
Of note: Screening Visit procedures can be performed on the same calendar day as Baseline 
Visit providing those are performed within 3 days before G-CSF administration 
 
Subjects who failed the screening procedures may be re-screened after consultation with the 
Sponsor. Re-screening should include all screening procedures listed in the protocol schedule 
of events, including re-consent signature. 

 
 
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5.2 
TREATMENT PERIOD  
5.2.1 Baseline Visit (Visit Day 0) 
Baseline visit should occur within 28 days after the screening visit and within 3 days prior to 
G-CSF administration (day -3 to Day 0). Only subjects who fully comply with the 
inclusion/exclusion criteria for the study will be eligible for participation. The following 
procedures will be performed at the Baseline Visit. A window of three days (-3 day to Day 0) 
is allowed for the procedures and assessments of this visit: 
 AE recording 
 Inclusion/Exclusion criteria review 
 Concomitant Medications review 
 Directed Physical Examination (if Baseline Visit Day 0 and Visit Day 1 are 
performed on the same day, Directed PE will be done prior to G-CSF 
administration) 
 Vital signs (supine blood pressure, heart rate, respiratory rate, temperature [°C] 
and room air SPO2) 
 12 Lead ECG 
 CBC with differential 
 Blood chemistry 
 CD34+ enumeration in PB  
 Weight (in kg) 
 Height (in cm) 
 Pregnancy test – serum or urine for all female patients of childbearing potential 
 
Of note: Baseline Visit Day 0 and Visit Day 1 can be done on the same calendar day 
providing activities related to Baseline are done before G-CSF administration 
 
5.2.2 Randomization (Part 2 only) 
During Part 1, subject numbers will be used to confirm enrollment at Baseline and to update 
the IWRS. During Part 2, enrollment of subjects will be performed up to 28 days following 
the screening evaluation, at the Baseline visit after confirmation that subject met study 
enrolment criteria.   
Subjects will be randomized using a 2:1 ratio to receive BL-8040 + G-CSF or Placebo + 
G-CSF, respectively. Randomization will use permuted blocks stratifying subjects by 
remission status (CR or PR) and baseline platelet count (<200 x 109/L or ≥200 x 109/L).  The 
IWRS will then assign a randomization number and the subject will be supplied and treated 
with the medication labeled with the applicable kit number. 

 
 
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5.2.3 Schedule of Treatment Period (Day 1 to Day 8) 
5.2.3.1 Visit Days 1-3  
Morning (8:00AM ± 2 hrs):  
 AE recording 
 Concomitant Medications review 
 Resource use and cost element data collection only for in patient  
 Subjects will be administered with G-CSF ~10 µg/kg (and maximum of 15 µg/kg) 
SC daily 
 Enrollment with IWRS in Day 1 onlya 
 
5.2.3.2 Visit Day 4 
Morning (8:00AM ± 2 hours):  
Subjects will undergo mobilization with G-CSF ~10 µg/kg (dose will be calculated according 
to local SoC and should not exceed 15 µg/kg) subcutaneously (SC).  
All procedures must be done before G-CSF injection, unless otherwise specified. 
 AE recording 
 Concomitant Medications review 
 CBC with differential 
 Blood chemistry  
 CD34+ enumeration in PBb 
 Resource use and cost element collection (before and after G-SCF administration) 
 Randomization using IWRS (only during Part 2, after G-SCF administration) 
 
Evening of Day 4 (8:00PM ± 2 hours):  
Subjects will receive either a single injection of BL-8040 1.25 mg/kg or placebo SC. During 
Part 1, only BL-8040 (no placebo) will be administered. Premedication should be 
administered within 1 hour prior to BL-8040/Placebo administration. All evening procedures 
should be done before BL-8040/placebo injection, unless otherwise specified.  
 Directed Physical Exam  
 AE recording 
 
a During Part 1, the IWRS system will be used for eligibility confirmation and stratification parameters entry as no 
randomization is conducted in Part 1. During Part 2, the IWRS system will provide treatment allocation. 
b Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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 Triplicate 12 Lead ECG:  
a. Pre-dose (up to 1 hour before BL-8040/placebo administration) and 
b. 30-45 minutes post-dose 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature [°C] and room 
air SPO2) 
 CBC with differential 
 Blood draw for PK assessment:  
a. 
Pre-dose (up to 1 hour before BL-8040/placebo administration)  
b. Post dosea (40-60 minutes and 2-6 hours)  
 Blood draw for ADA assessment (Pre BL-8040/Placebo dosing up to 1 hour 
before) 
 Blood draw for assessment of Complement Activation  
a. 
Pre BL-8040/placebo dosing up to 1 hour before  
b. 2 hours post dosinga ±15 minutes 
 Blood draw for assessment of serum tryptase/Mast Cells Activation  
a. 
Pre BL-8040/placebo dosing up to 1 hour before dosing  
b. 2 hours post dosinga ±15 minutes  
c. 
Only in case of anaphylaxis unscheduled sample for tryptase will be 
collected within 2 hours from the event  
 Subjects will receive a single dose of BL-8040/placebo.   
 
5.2.3.3 Visit Day 5 
PK assessment 
Blood draw for PK assessment: 12 ± 2 hrs post second dose of BL-8040/Placebo 
administration and before apheresis 
 
Morning (8:00AM ± 2 hours): A 5th dose of G-CSF will be administered prior to first 
apheresis. Subjects will then undergo apheresis per institutional protocol (4 blood volumes 
±10%/apheresis). 
The below procedures should be done before G-CSF injection: 
 Directed Physical Exam  
 AE recording 
 Concomitant Medications review 
 Weight   
 Triplicate 12 Lead ECG (up to 1 hour prior to G-CSF) 
 Vital signs  
 
a Post dose defined as end time of administration 

 
 
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 CBC with differential   
 Coagulation test  
 Blood chemistry 
 CD34+ enumeration in PBa 
 Resource use and cost element data collection (Part 2)  
 
The below procedures should be done after G-CSF injection: 
 Apheresis - Subjects will then undergo a 4 blood volumes ±10% apheresis (12 
hours ± 2 hours post first dose of BL-8040/Placebo administration ) - see section 
5.2.4) 
 CD34+ enumeration in apheresis producta 
 Lymphocyte subsets in apheresis product (Part 2) 
 Multiple Myeloma Cells in the apheresis product (Part 2) 
 Resource use and cost element data collection (Part 2)  
 
5.2.3.4 Visit Day 6 
This visit will be conducted only for: 
 Subjects who did not reach the goal of collection of ≥6 x 106 CD34+ cells/kg for 
mobilization after one apheresis. 
 All subjects with moderate or severe renal impairment at Screening as defined by 
GFR <50 mL/min/1.732 calculated by MDRD equation regardless of the amount of 
cells collected in the first apheresis. 
 
For all patients who did not reach the collection goal in the first apheresis, a 6th dose of 
SC G-CSF ~10 µg/kg (and maximum of 15 µg/kg) will be administered prior to the second 
apheresis in an effort to reach a total of ≥6 x 106 CD34+ cells/kg. The following procedures 
will be performed: 
(Morning 8:00AM ± 2 hrs): Subjects will be administered with G-CSF ~10 µg/kg (and 
maximum of 15 µg/kg) SC 
The below procedures should be done before G-CSF injection: 
 
AE recording 
 
Concomitant Medications review  
 
CBC with differential 
 
Blood chemistry 
 
CD34+ enumeration in PBa 
 
Resource use and cost element data collection (Part 2) 
 
a   Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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The below procedures should be done after G-CSF injection: 
 
Apheresis - four blood volumes ±10% apheresis - See section 5.2.4 
 
CD34+ enumeration in apheresis producta 
 
Lymphocyte subsets in apheresis product (Part 2) 
 
Multiple Myeloma Cells in the apheresis product (Part 2) 
 
Resource use and cost element data collection (Part 2) 
 
For subjects with moderate or severe renal impairment at Screening as defined by GFR 
<50 mL/min/1.732 calculated by MDRD equation, the below procedures should be done: 
 CBC with differential  
 Blood chemistry 
 Vital signs 
 12 Lead ECG local assessment 
 
The results of serum creatinine and GFR, as well as any other clinically significant 
change, should be reviewed and assessed by the investigator. In case of abnormal 
clinically significant changes, it should be reported as AE and, in addition to the study 
procedures, subjects should be followed on a weekly basis until recovery or stabilization 
by the following procedures: 
 
Biochemistry with GFR assessment 
 
CBC with differential 
 
Vital signs 
 
12 Lead ECG local assessment 
 
AE assessment 
 
For subjects that did not reach the collection goal and present with BL-8040/placebo 
related clinically significant changes according to investigator assessment, a second 
administration will not be administered in the evening. The subjects will then be 
considered as early terminated and Visit 13 (Termination/Early Termination) procedures 
should be followed. 
 
Of note: For patients with moderate or severe renal impairment at Screening, who also did 
not reach the collection goal, all of the above-listed procedures should be performed (CBC 
and biochemistry should be done only once) 
 
a     Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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Only if the subject does not reach the collection goal for mobilization (≥6.0 x 106 CD34+ 
cells/kg), a second dose of BL-8040/placebo (in Part 1, only BL-8040 will be administered) 
will be administered in the evening.  
Evening (8:00PM ± 2 hrs):  
Premedication should be administered within 1 hour prior to BL-8040/Placebo 
administration. 
 
The below procedures should be done before BL-8040/placebo injection, unless otherwise 
specified: 
 Directed Physical Exam  
 AE recording 
 Triplicate 12 Lead ECG Day 4 evening:  
a. 
Pre-dose (up to 1 hour before BL-8040 administration) and  
b. 30-45 minutes post-dosea 
 Vital signs  
 CBC with differential 
 IWRS for cases of a 2nd dose of BL-8040/Placebo 
 Subjects will receive SC injection of BL-8040/placebo  
 Blood draw for PK Assessment:  
a. 
Pre-dose (up to 1 hour before BL-8040/placebo administration),  
b. Post dosea (40-60 minutes and 2-6 hours) 
 Resource use and cost element collection (Part 2) (before and after BL-
8040/placebo administration) 
 
5.2.3.5 Visit Day 7 
This visit will be conducted only in subjects who did not reach the goal of collection after 
two apheresis procedures and received a second dose of BL-8040/placebo on Visit Day 6. 
PK assessment 
Blood draw for PK assessment: 12 ± 2 hrs post second dose of BL-8040/Placebo 
administration and before apheresis. 
 
Morning (8:00AM ± 2 hours): A 7th dose of SC G-CSF ~10 µg/kg (and maximum of 
15 µg/kg) will be administered prior to a third apheresis. 
 
a Post dose defined as end time of administration 

 
 
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The below procedures should be done before G-CSF injection: 
 Directed Physical Exam 
 Review AE 
 Concomitant Medications review 
 Triplicate 12 Lead ECG  
 Vital signs 
 CBC with differential 
 Coagulation Test 
 Blood chemistry 
 CD34+ enumeration in PBa 
 Resource use and cost element data collection (Part 2) 
 
The below procedures should be done after G-CSF injection: 
 Apheresis - four blood volumes ±10% apheresis (12 hours ± 2 hours post second dose 
of BL-8040/Placebo administration ) - See section 5.2.4 
 CD34+ enumeration in apheresis producta 
 Lymphocyte subsets in apheresis product (Part 2) 
 Multiple Myeloma Cells in the apheresis product (Part 2) 
 Resource use and cost element data collection (Part 2) 
 
5.2.3.6 Visit Day 8 
This visit will be conducted only for: 
 All subjects who did not reach the collection goal for mobilization (≥6.0 x 106 CD34+ 
cells/kg) after three apheresis procedures. In this case, an 8th dose of G-CSF will be 
administered prior to fourth apheresis.  
 All subject with moderate or severe renal impairment at Screening as defined by GFR 
of <50 mL/min/1.732 calculated by MDRD equation, who received a second dose of 
BL-8040/placebo, regardless of the amount of cells collected in the apheresis. 
 
For subjects who did not reach the goal of collection the following procedures will be 
performed: 
Morning (8:00AM ± 2 hours): A 8th dose of SC G-CSF ~10 µg/kg (and maximum of 
15 µg/kg) will be administered prior to a third apheresis. 
 
a Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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The below procedures should be done before G-CSF injection: 
 
Directed physical examination 
 
Review AEs 
 
Review of Concomitant medications 
 
Vital signs 
 
CBC with differential 
 
Blood chemistry 
 
CD34+ enumeration in PBa 
 
Resource use and cost element data collection (Part 2) 
 
The below procedures should be done after G-CSF injection: 
 
Apheresis- four blood volumes ±10% apheresis 
 
CD34+ enumeration in apheresis producta 
 
Lymphocyte subsets in apheresis product (only during Part 2) 
 
Multiple Myeloma Cells in the apheresis product (only during Part 2) 
 
Resource use and cost element data collection (Part 2) 
 
For subjects with moderate or severe renal impairment at Screening as defined by GFR 
of <50 mL/min/1.732 calculated by MDRD equation, the below procedures should be done: 
 
CBC with differential 
 
Blood chemistry 
 
Vital signs 
 
12 Lead ECG local assessment 
 
The results of serum creatinine and GFR, as well as any other clinically significant 
change, should be reviewed and assessed by the investigator. In case of abnormal 
clinically significant changes, it should be reported as AE and, in addition to the study 
procedures, subjects should be followed on a weekly basis until recovery or stabilization 
by the following procedures: 
 
Biochemistry with GFR assessment 
 
CBC with differential 
 
Vital signs 
 
12 Lead ECG local assessment 
 
AE assessment 
 
a   Local assessment in both parts. For Part 2, sample will be analyzed at local and central laboratory. 

 
 
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Rescue procedure: 
Subjects who fail to collect the required CD34+ cells/kg after four apheresis sessions (the 
requirements will be defined according to local SoC) will be able to receive a rescue 
procedure (see section 5.2.5) per investigator preference in accordance with standard of care 
guidelines and may reattempt re-mobilization after at least  7 day “rest/wash-out” period (7 
days from the last dose of BL-8040/placebo). 
5.2.4 Apheresis procedure 
Apheresis will be performed according to local practice guidelines at each study site using a 
standard 4 blood volumes ±10%. Venous access via an apheresis catheter of the center’s 
choice will be used and may be prepared/placed in advance of the first apheresis day. 
Three samples of apheresis product will be obtained for local and central assessment by 
FACS analyses (the apheresis product volume and the absolute number of CD34+ cells per 
unit volume will be measured and recorded in the CRF to calculate the total yield of CD34+ 
cells/kg).  
Processing and storage of apheresis product will be done according to the standardized 
procedures of each study site.  
5.2.5 Rescue Procedure 
Subjects who fail to collect the cells required per local SoC after four apheresis sessions will 
be managed per Investigator preference in accordance with standard of care guidelines. They 
may re-attempt mobilization per standard of care after at least 7 days “rest/wash-out” period 
(from the last dose of BL-8040/placebo). Subject who failed to collect enough CD34+ cells in 
four apheresis sessions will continue to be followed according to the protocol schedule visits.  
All cost element and resource use related to rescue procedure will be collected and captured 
in the eCRF.  
5.2.6 Post Treatment Period 
5.2.6.1 Visit 9: Conditioning Treatment Pre-transplantation 
Following successful mobilization and collection of adequate CD34+ cells for auto-HCT, 
study participants will be admitted to the hospital for preparative (conditioning) 
chemotherapy. Conditioning must occur within 5 weeks after the last apheresis session  
The pre-transplant conditioning chemotherapeutic regimens (± total body irradiation (TBI)) 
used in this trial may include: 
• Melphalan (200 or 140 mg/m2)  
• BEAM  
• BuCy  
• Arsenic/Melphalan  
• Busulfan/Melphalan  

 
 
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Selection of the appropriate conditioning regimen shall be at the discretion of the 
Investigator. Local standard of care guidelines will be followed. 
 
The procedures and evaluations at Visit 9 should be done within 3 days before beginning of 
conditioning: 
 Complete Physical Exam 
 Concomitant Medications review 
 Vital signs 
 CBC with differential 
 Blood Chemistry 
 Blood draw for ADA assessment 
 Pregnancy test (urine/serum) 
 Resources use and cost elements data collection 
 
5.2.6.2 Visit 10: Transplantation and Immediate Post-Transplantation Follow-Up (Day 
1-29 Post Transplantation) 
Transplantation will occur ~24 hrs after the completion of the conditioning regimen and no 
later than 5 weeks after the last apheresis session.  
Transplantation should be performed using the collected CD34+ cells. A minimum of >2 x 
106 CD34+ cells/kg must be transplanted; however, more cells may be transplanted up to the 
full amount collected at the Investigator’s discretion. Excess CD34+ cells may be stored for 
later use, per Investigator preference. The number of cells transplanted will be recorded in the 
CRF.  
Local guidelines for transplantation will be followed.  
Post-transplantation follow-up begins the day after cell transplantation and lasts until the time 
of neutrophil and platelet engraftment (whichever comes later). Engraftment will be assessed 
by daily CBC of PB unless engraftment period is conducted as an outpatient – in that case 
only neutrophils and platelets counts will be collected and documented in the CRF together 
with any usage of medications during this period. 
 
Engraftment is defined as follows: 
• Neutrophil engraftment: Defined as the first of 3 consecutive days of ANC ≥0.5 x 
109/L or ≥1.0 x 109/L for 1 day following the conditioning-regimen-associated nadir. 
• Platelet engraftment: Defined as the first of 3 consecutive measurements of platelet 
count ≥20 x 109/L following the conditioning regimen associated nadir and without 
platelet transfusion support for 7 days 
• Of note: For subjects receiving transfusion for any reason other than platelet count 
<20 x 109/L, who already meet the platelet engraftment criteria as above, this 
transfusion will not affect the platelets engraftment assessment date (e.g. transfusion 
for any specific procedures or as part of SoC in specific institutions, etc.) 

 
 
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• Actual engraftment days will be calculated according to CIBMTR guidelines (See 
Appendix D). 
 
The procedures and evaluations at Visit 10 are as follows:  
 Day of transplantation - Before Transplant 
 Directed Physical Exam  
 Concomitant Medications review 
 Vital signs  
 CBC with differential 
 Blood chemistry  
 Resources use and cost elements data collection 
 
 Day 1-29 post-transplant: 
Procedures to be done daily beginning the day after transplantation until engraftment: 
 Neutrophil and platelets assessment 
a. For in-patient, CBC with differential will be collected daily and recorded 
accordingly until engraftment  
b. For patient that are followed up as out-patient, assessment will be done 
according to local SoC and recorded within the CRF 
 Recording administration of G-CSF, other growth factors or blood and platelets 
transfusion will be fully documented within CRF   
 Resources use and cost elements data collection (only for inpatients) 
 
5.2.7 Visit 11-13: Graft Durability and Core Study Termination Visit 
Following transplantation, subjects will be monitored for graft durability in PB. Counting 
begins on transplantation day, which is considered as Day 0. 
 
Graft durability is defined as maintenance of at least 2 of the following 3 criteria:  
• Platelet count ≥50,000 (50 x 109/L) without transfusion for at least 2 weeks. 
• Hemoglobin level ≥10 g/dL with no erythropoietin support or transfusions for at least 
1 month. 
• Absolute neutrophil count (ANC) ≥1,000 (1.0 x 109/L) for 1 week. 
 
Bone marrow biopsy will be performed on Day 100 (Visit 13) if there is no biochemical 
evidence of relapse. 
 

 
 
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5.2.7.1 Visit 11: Day 30 Post Transplantation (± 3 days) 
The procedures and evaluations will be as follows: 
 Concomitant Medications review - only disease related medications should be 
reported. 
 Vital signs  
 CBC with differential 
 Blood chemistry 
 Blood Draw for ADA  
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation - 24 hours 
urine collection is required  
 Serum Free Light Chain (FLC) 
 Engraftment assessment by platelets and neutrophils count 
 Resource use and cost elements data collection (only during Part 2)  
 
5.2.7.2 Visit 12: Day 60 Post Transplantation (±7 days)  
Visit procedures will include as follows: 
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation-24 hours 
urine collection is required  
 Serum Free Light Chain (FLC) 
 Concomitant Medications review-only disease related medications should be 
captured. 
 Vital signs 
 ECOG performance status (see Appendix B) 
 CBC with differential 
 Blood chemistry 
 Relapse Free Survival (RFS) and overall survival (OS) assessment 
 Resources use and cost elements data collection (only during Part 2) 
 
5.2.7.3 Maintenance Treatment 
Subjects will be allowed to receive maintenance treatment with lenalidomide, bortezomib, 
pomalidomide or a similar FDA-approved maintenance therapy, beginning on Day 60 post 
transplantation. Patients should not receive maintenance therapy within the first 60 days from 
transplantation, except in the case of confirmed disease relapse. Data should be recorded 
within the CRF in a special assigned page for maintenance treatment.  

 
 
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5.2.7.4 Visit 13: Day 100 Post Transplantation (± 7 days), Termination/Early 
Termination Visit 
Termination visit procedures: 
 Concomitant Medications review- only disease-related medications should be 
captured. 
 Complete physical examination 
 Vital signs 
 ECOG performance status (see Appendix B) 
 CBC with differential 
 Blood chemistry 
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation-24 hours 
urine collection is required  
 Serum Free Light Chain (FLC) 
 Bone marrow biopsy will be performed on Day 100 (Visit 13) if there is no 
biochemical evidence of relapse. Relapse Free Survival (RFS) and overall survival 
(OS) assessment 
 Resources use and cost elements data collection (only during Part 2) 
 
All information for early termination will be documented in the source documents. Only one 
reason (the most severe) for early discontinuation should be recorded in the CRF. If one of 
the reasons for discontinuation is an AE, this should be chosen as the reason.  Patients who 
discontinue study treatment will continue to be followed as per protocol in case they agreed 
to it in the ICF. Every effort should be made to follow-up these subjects until resolution of 
the AE and for the entire period of the study follow-up (up to 5 years). 
Data collection at these visits should primarily be guided by the need to protect subject safety 
and well-being.   
In case the subject decides to discontinue the follow-up, the reason for discontinuation should 
be reported at the relevant CRF visit page. 
A patient who received G-CSF and discontinued before receiving BL-8040 could potentially 
be rescreened assuming washout period from G-CSF is completed.  

 
 
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5.2.8 Long Term Disease Assessment Follow-Up Post Transplantation 
5.2.8.1 Visits 14-16: Day 180 (6 months) - Day 360 (12 months) 
Visits 14-16 will be conducted at 180 days (±14 days), 270 days (±14 days) and 360 days 
(±14 days) post-transplantation. Visit procedures will include: 
 ECOG performance status 
 CBC with differential 
 Blood chemistry 
 Review of Concomitant Medications - only disease-related medications should be 
captured.  
 Monoclonal Protein (M) in serum (SPEP) and serum immunofixation 
 Monoclonal Protein (M) in urine (UPEP) and urine immunofixation - 24 hours 
urine collection is required  
 Serum free light chain (FLC) 
 Relapse Free Survival (RFS) and overall survival (OS) assessment 
 
5.2.8.2 Visit 17 and up to 5 years  
After completing 12 months follow-up visits, subjects will be contacted by phone every 6 
months (± 30 days) in order to assess disease status, concomitant medications (only disease-
related medications should be captured)  and assessment for Relapse Free Survival (RFS) and 
Overall Survival (OS), beginning in Visit 17 at 18 months until 5 years from last patient 
randomization day.  
5.2.8.3 Unscheduled Visits  
An unscheduled visit may be performed at any time of the study at the subject's request or as 
deemed necessary by the Investigator. The date and reason for the unscheduled visit will be 
recorded. AE monitoring and concomitant medication recording will be performed by the 
Investigator. Other procedures and evaluations will be completed as deemed necessary by the 
Investigator and may include (but not be limited to) laboratory safety tests, vital signs and 
physical examination. 
5.3 
SAFETY ASSESSMENTS 
Safety assessments will be based on changes from Baseline of clinical signs and symptoms 
reported by the subject or observed by the Investigator, including AEs, concomitant 
medication use, treatment compliance, tolerability (e.g. dropouts due to AEs), vital signs, 
ECGs, physical examination, laboratory safety assessments and clinical evaluation of 
leukostasis. 
5.3.1 Adverse Events (AEs) 
All AEs will be collected starting from ICF signature and up to 30 days from the last dose of 
study drug. 

 
 
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Any new systemic AE that occurs between scheduled assessment visits should be brought to 
the attention of the Investigator and recorded in the subject’s medical file and on the 
appropriate CRF page. 
AEs will be reported and graded in accordance with the latest NCI-CTCAE version (currently 
version 5.0) and coded by Data Management using the latest version of MedDRA (currently 
version 20.1). 
All information on use of resources to manage the AE will be collected. This includes drug 
use, time of the physician and nurse, consumables, drugs, imaging and laboratory tests. 
Post-conditioning and transplantation neutropenia and thrombocytopenia are expected 
findings and therefore there is no need to report them as adverse events unless the severity is 
not as expected with these procedures according to PI assessment. Concomitant medication 
for those events should be recorded in concomitant medication page in CRF. 
5.3.2 Concomitant Medications 
Concomitant medication use will be recorded at the Screening visit and will include 
medications taking by the patient within 12 months before screening.   
All concomitant medication will be recorded up to Visit 10, inclusive. 
Starting from Visit 11, only myeloma/disease-related Concomitant Medications will be 
recorded, including among others stimulating factors, transfusions, myeloma-specific 
chemotherapy, etc.  
5.3.3 Vital Signs 
During Part 1, the lead-in period, as well as Part 2, vital signs will be measured at: 
 Screening 
 Baseline  
 Day 4, evening, before BL-8040/placebo administration  
 Day 5, morning, before G-CSF administration  
 Day 6, morning before G-CSF administration   
 Day 6, evening, before BL-8040/placebo administration  
 Day 7 and Day 8, morning, before G-CSF administration 
 

 
 
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Vital signs will also be measured at: 
 Conditioning visit (Visit 9), before procedure  
 Transplantation day, before procedure  
 Day 30 Post-Transplantation (± 3 days) 
 Day 60 Post-Transplantation (± 7 days) 
 Day 100 Post-transplantation (± 7 days) 
 Day 6 (morning) for subjects with moderate or severe renal impairment 
 Day 8 (morning) for subjects with moderate or severe renal impairment, who 
received a second dose of BL-8040/placebo.  
 
Vital signs will include blood pressure, pulse rate, body temperature, oxygen saturation and 
respiration rate after at least 5 minutes rest as per standard practice at the investigational site. 
Significant findings noticed after the start of study drug, which meet the definition of an AE, 
must be recorded on the AE CRF.  
5.3.4 Electrocardiogram 
 During Part 1, the lead-in period, as well as Part 2, ECG will be taken at 
Screening and at Baseline (Day 0).  
 On Day 4, evening, ECG will be taken in triplicate prior to study drug 
administration (up to 1 hour pre-dose) and 30-45 minutes post dosea 
 On Day 5, morning, ECG will be taken in triplicate prior to apheresis and G-CSF 
administration (up to 1 hour pre G-CSF dose) 
 On Day 6, evening, ECG will be taken in triplicate prior to study drug 
administration (up to 1 hour pre-dose) and 30-45 minutes post dosea 
 On Day 7, morning, ECG will be taken in triplicate prior to apheresis and G-CSF 
administration (up to 1 hour pre G-CSF dose). 
 On Day 6, morning, ECG will be taken in triplicate for subjects with moderate or 
severe renal impairment 
 On day 8, morning, ECG will be taken in triplicate for subjects with moderate or 
severe renal impairment if who received a second dose of BL-8040/placebo 
 
The subject should rest for at least 10 minutes before measurement is taken. In cases were 
ECG coincide with blood collection or vital signs measurement, ECG recording should be 
performed first. 
Interval between triplicate ECG is one minute. 
 
a   Post dose defined as end time of administration 

 
 
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The following assessment will be done as part of the ECG:  
 Ventricular rate / Heart rate (beats per minute) 
 RR interval (milliseconds) 
 PR interval (milliseconds) 
 QRS duration (milliseconds) 
 QT interval (milliseconds) 
 QTcF interval (milliseconds) 
 
ECG printouts will be evaluated by the Investigator or designee, signed and dated and filed in 
the source documentation file. All ECG but those of Day 6 and 8 for subjects with moderate 
or severe renal impairment will be sent automatically to a central reading center. In case of 
clinically significant pathological finding an alert will be sent to each site and to the Sponsor 
Medical monitor.  
Day 6 and 8 ECGs for subjects with moderate or severe renal impairment will be done locally 
evaluated by the Investigator or designee, signed and dated and filed in the source 
documentation file.  
5.3.5 During Parts 1 and 2 
Complete Physical Examination 
Will include assessment of head, lungs, cardiovascular system, abdomen, musculoskeletal 
system, skin, lymph nodes, neurological system and, where appropriate, other body systems as 
indicated in the study schedule. 
A complete physical examination will be conducted at Screening, Visit 9 (Conditioning) and 
Visit 13 (Termination/Early Termination visits).  
Directed Physical Examination 
During a directed PE, particular attention should be focused on identifying possibly G-CSF 
and study drug related adverse events and managing these AEs effectively. 
A directed physical examination will be conducted:  
 at Baseline (Day 0).  
In case Baseline visit Day 0 and Visit Day 1 performed on the same day, Directed PE 
will be done prior G-CSF administration. 
 on Day 4 before BL-8040/placebo administration.  
 on Day 5 before G-CSF administration.  
 on Day 6 before BL-8040/placebo administration. 
 on Days 7 and 8 before G-CSF administration. 
 on Transplantation day prior to transplantation.  
 Day 30 Post-Transplantation (± 3 days). 
 

 
 
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Information about the physical examination must be presented in the source documentation at 
the study site. Significant findings that are present prior to the start of study drug must be 
included in the Relevant Medical History/ Current Medical Conditions CRF. Significant 
findings or deterioration of pre-existing condition made after ICF signing that meet the 
definition of an AE must be recorded on the AE CRF module if occurred until Day 30 post 
treatment.  
5.3.6 Laboratory Assessments  
Complete CBC and differential 
During Parts 1 and 2, CBC (see Table 1) will be performed by local laboratories at the 
participating sites at: 
 Screening  
 Baseline (Visit Day 0) 
 Day 4, morning and evening, pre-dose (of G-CSF and study drug administration, 
respectively) 
 Day 5, morning pre-dose (of G-CSF and study drug administration, respectively)  
 Day 6, morning and evening, pre-dose (of G-CSF and study drug administration, 
respectively) 
 Days 7 and 8, morning, G-CSF pre-dose (of G-CSF At Visit 9 - Conditioning visit prior 
to treatment  
 At Visit 10 - Transplantation day 
 Visits 12-16: 
o Day 30 Post-transplantation (± 3 day) 
o Day 60 Post-Transplantation (± 7 days) 
o Day 100 Post-Transplantation (± 7 days) 
o Day 180 Post-Transplantation (± 14 days) 
o Day 270 Post-Transplantation (± 14 days) 
o 1 Year Post-Transplantation (± 14 days) 
 For subjects with moderate or severe renal impairment, on Day 6, morning, and Day 8, 
morning (Day 8 only if a second dose of BL-8040/Placebo was administered)   
 
Neutrophils and Platelets assessment only 
 Day 1– Day 29 Post-Transplant or until engraftment, whichever occurs first. For in-
patient, assessment should be performed on a daily basis; for out-patient, assessment 
should be performed according to local SoC.  
 
Blood Chemistry 
Blood chemistry laboratory tests (see Table 1) will be taken on: 
 Screening  
 Baseline (Visit Day 0) 
 Day 4, morning, before G-CSF administration   
 Days 5, 6, 7, and 8, morning, before G-CSF administration  

 
 
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 At Visit 9 - Conditioning visit  
 At Visit 10 - Transplantation day 
 Visits 12-16: 
o Day 30 Post-transplantation (± 3 day) 
o Day 60 Post-Transplantation (± 7 days) 
o Day 100 Post-Transplantation (± 7 days) 
o Day 180 Post-Transplantation (± 14 days) 
o Day 270 Post-Transplantation (± 14 days) 
o 1 Year Post-Transplantation (± 14 days) 
 For subjects with moderate or severe renal impairment, on Day 6, morning, and Day 
8, morning (Day 8 only if a second dose of BL-8040/Placebo was administered)  
 
Coagulation Test 
INR and PT/aPTT will be performed at Screening and on Days 5 and 7, before apheresis.  
 
Other assessments 
 Blood Serology assessment will be performed at Screening. 
 Monoclonal (M) Protein in Serum, Monoclonal (M) Protein in Urine (i.e. UPEP/SPEP 
with Immunofixation) and Serum Free Light Chain (FLC) will be taken at Screening, 
Day 30, 60, 100, 180, and Day 270, and 12 months post-transplantation. 
 Urinalysis will be done at Screening visit. 
 Laboratory safety sampling will include the parameters listed below. The exact time-
points for each one of the tests are specified in Appendix A. 
 
Table 1: 
Laboratory Assessments 
Evaluations 
Parameters 
Hematology 
Red blood cell count, hemoglobin (HGB), hematocrit (HCT), mean cell hemoglobin 
(MCH), mean cell hemoglobin concentration (MCHC), mean corpuscular volume 
(MCV), white blood cell (WBC) count and differential (including number of blasts, 
neutrophils and lymphocytes) and platelet count. 
Chemistry  
Electrolytes: sodium (Na+), potassium (K+), calcium and phosphorus  
Liver function tests: AST, ALT, ALP, total bilirubin  
Kidney function tests: creatinine, BUN  
Other: glucose, uric acid, LDH. 
Coagulation 
Pro-thrombin time (PT)/INR and activated partial thromboplastin time (aPTT) 
Serologya  
HIV antibodies (HIV1 and HIV2), Hepatitis B surface antigen (HBsAg) and 
Hepatitis C antibody (Hep C Ab). 
Urinalysis 
Bacteria, Glucose, protein, Bilirubin, Leukocyte, RBC, Cast, Ketones, Specific 
Gravity, Color, Nitrites, Crystals, pH. 
Other  
Pregnancy test - a serum/urine β-HCG pregnancy test for women of childbearing 
potential. 
 
a To be collected at screening only. 

 
 
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Laboratory safety test abnormalities, which arise after study drug administration, will be 
repeated as clinically indicated until the values return to normal or until the etiology has been 
determined and the condition considered stable. Abnormal laboratory test results that are 
considered to be clinically significant by the Investigator and are up to 30 days from the last 
dose of study drug should be reported as an AE in the AE CRF module.  
Laboratory results will be reported to the Investigator or designee who will review, sign and 
date abnormal laboratory findings for clinical significance. The Investigator will note any 
laboratory test results of clinical concern or values that were outside normal ranges and 
provide details of the relationship to investigational product and the action taken. If a change 
in a laboratory value represents a medical condition, the medical condition will be listed in 
the AE record.  
5.3.7 Assessment of Anti-Drug Antibodies (ADA), Complement Activation and Mast 
Cell Activation 
Tests for mast cell activation and complement activation will be performed by the central 
laboratory and will be collected on Day 4 (evening) - before study drug administration (up to 
1 hour pre-dose), and 2 hours following administrationa (±15 minutes). Testing will be 
performed in Part 1 and Part 2 of the study. Details are available in the study “Laboratory 
Manual”. 
Testing for ADA will be performed by a central laboratory and will be collected on Day 4 
(evening)  - before BL-8040 administration (up to 1 hour pre-dose), on Visit 9 before 
chemotherapy administration and on Visit 11.                                                                                                      
5.4 
EFFICACY ASSESSMENTS 
5.4.1 CD34+ Cell Enumeration in the Apheresis Product 
CD34+ cell enumeration in the apheresis product will be performed both by the local and 
central laboratories (Part 2), once a day, on Days 5-8. Decisions with regard to continuing 
apheresis procedures will be made based on local laboratory results.  
5.4.2 CD34+ Cell Enumeration in Peripheral Blood (PB) 
CD34+ cell enumeration in PB should be collected before G-CSF administration. This 
assessment will be performed at local laboratory during Parts 1 and 2 and will also be 
performed by central laboratory during Part 2 only. The assessment will be done at Baseline 
and once a day on Days 4-8. 
 
a Post dose defined as end time of administration 

 
 
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5.4.3 Assessment of Engraftment by CBC 
Hematology laboratory tests for the purposes of safety and assessment of engraftment will be 
taken: 
 At Visit 9 - Conditioning visit  
 At Visit 10: 
o At Transplantation day 
o Day 1 – Day 29 Post-Transplantation (for out-patients, assessment will be   
performed according to local SoC) - only neutrophils and platelets will be 
recorded during this period 
 Visits 12-16: 
o Day 30 Post-transplantation (± 3 days) 
o Day 60 Post-Transplantation (± 7 days) 
o Day 100 Post-Transplantation (± 7 days) 
o Day 180 Post-Transplantation (± 14 days) 
o Day 270 Post-Transplantation (± 14 days) 
o 1 Year Post-Transplantation (± 14 days) 
5.5 
DISEASE STATUS ASSESSMENT BY BONE MARROW BIOPSIES 
Bone marrow biopsies will be performed at screening only for CR/sCR patients. Biopsy 
performed within 30 days prior to signing the ICF will be acceptable and no new biopsy will 
be required. A second bone marrow biopsy will be performed at Visit 13 (Day 100 Post 
Transplantation) if biochemical tests do not show evidence of relapse. Further unscheduled 
assessment may be performed upon Investigator’s discretion. 
5.6 
PK ASSESSMENTS 
In Part 1, blood samples for PK analysis of BL-8040 or its metabolites will be collected on 
Day 4 and Day 6 before and at 0.25, 0.5, 1, 2, 4, 8 and 12 hours after BL-8040 
administration. Samples should be collected before the first apheresis on Days 5 and 7 (and 
before G-CSF injection). 
The time windows for PK collections in Part 1 are described in detail in the study Laboratory 
Manual.  
In Part 2, blood samples for PK analysis of BL-8040 or its metabolites will be collected on 
Day 4 at pre-dose of BL-8040 and at 40-60 minutes, 2-6 hours and 10-12 hours post BL-8040 
administration. The 12 ±2 hours PK sample should be collected on Day 5 before the apheresis 
(before G-CSF injection). The same sampling scheme will be followed for Day 6, if 
applicable.    
The exact sampling time relative to BL-8040 administration will be recorded in the CRF. 
5.7 
BLOOD SAMPLING AND PROCESSING  
Samples will be collected for safety and efficacy analysis, ADA titers, complement and mast 
cell activation and PK at the time-points indicated in Appendix A.  
Instructions for the collection, processing, storage and shipment of samples are detailed in the 
Laboratory Manual provided by the Sponsor. 

 
 
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 Analgesic medication may be added to the premedication regimen at the discretion of 
the treating physician. 
 BL-8040 is to be administered at a dose of 1.25 mg/kg by slow subcutaneous injection 
of at least 2 minutes per syringe.  If the volume to be administered exceeds 2 mL then 
the injection should be divided into two or more syringes to be administered at 
different injection locations.  
 Transient hypotension was witnessed in several cases following the initial treatment 
with BL-8040. Therefore, caution should be taken with the use of negative 
chronotropic drugs such as beta blockers. When appropriate, beta blocker should be 
replaced with non-negative chronotropic drugs. 
 All patients are to remain under surveillance for 2 hours after the first administration 
of BL-8040. Patients receiving an additional dose of BL-8040, should remain under 
observation for 1 hour after the subsequent administration of BL-8040. 
 BL-8040 should only be administered when personnel and therapies are immediately 
available for the treatment of anaphylaxis and other hypersensitivity reactions, should 
they occur. 
 
Site of Injection:  
The BL-8040 or placebo injections should be given in different areas of the body in case of a 
divided dose or if a second dose is needed. If the dose volume after reconstitution is higher 
than 2 mL, injections should be divided in order to maintain injection volume under 2 mL; at 
the discretion of the Investigator, a single dose administration may be divided and injected 
into more than one injection site. The same instructions are applicable for the randomization 
period of the study. 
Doses can be injected SC in the arms, legs or abdomen according to the Investigator 
discretion. Subjects should stay ~1 hour after injection to follow up any possible adverse 
event. 
Dosing calculation: 
The patient’s actual body weight, collected at Baseline, will be used to calculate the dosage 
of BL-8040 administered.  
The volume of study drug to be administered will be calculated as follows: 
The formula to calculate volume of injection (mL) is:   
                                         Patient weight (kg) x drug dose (1.25 mg/kg) 
               36.5 mg/mL  
 
Results should be rounded to one decimal place. For example: For a patient that weighs 70 
kg, the dose calculation is as follows:  
(70 kg ×1.25 mg/kg)/ (36.5 mg/mL) = 2.39 mL. Round one decimal place. The volume of 
BL-8040 to inject is 2.4 mL, divided into two injections. 
Table 2 shows the volumes to be injected for different patient weights. 

 
 
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Table 2:  Injected Volume based on Patient’s Weight 
Subject’s Weight (kg) 
Volume to Inject (mL) 
40-42 
1.4 
43-45 
1.5 
46-48 
1.6 
49-51 
1.7 
52-54 
1.8 
55-56 
1.9 
57-59 
2.0 
60-62 
2.1 
63-65 
2.2 
66-68 
2.3 
69-71 
2.4 
72-74 
2.5 
75-77 
2.6 
78-80 
2.7 
81-83 
2.8 
84-86 
2.9 
87-89 
3.0 
90-91 
3.1 
92-94 
3.2 
95-97 
3.3 
98-100 
3.4 
101-103 
3.5 
104-106 
3.6 
107-109 
3.7 
110 
3.8 
 
6.2.2 G-CSF  
During the G-CSF administration period, each patient will receive ~ 10 μg/kg (maximum of 
15 μg/kg) G-CSF in the morning daily for up to a total of 8 days, but a minimum of 5 days, 
depending on the results of each apheresis. The dose of G-CSF administered will be based on 
the patient’s actual body weight assessed at Baseline. In case dose should be rounded to vial 
volume, the final dose will be administered according to institution SoC. 
G-CSF will be administered as a SC injection. Administration of G-CSF will be documented 
in the CRF. G-CSF may be given at the clinic, by a visiting nurse, or by patient self-
administration at home per patient/institutional preference and local practice pattern.  
Following transplantation, G-CSF (~5 μg/kg daily) may be started according to local SoC and 
may continue until the ANC is ≥0.5 x 109/L for 3 days or ≥1.0 x 109/l for 1 day. 
Administration of G-CSF will be documented in the CRF.  
The number of units of G-CSF injected will be recorded.  

 
 
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6.3 
MANUFACTURING OF STUDY MEDICATION 
6.3.1 BL-8040  
BL-8040 drug substance (motixafortide (INN), formerly called 4F-benzoyl-TN14003 or 
BKT140) is a synthetic cyclic peptide. It is a white to off-white powder, freely soluble in 
water and in 0.45% Sodium Chloride (half normal saline).  
BL-8040 drug product is formulated as a sterile and non-pyrogenic lyophilized powder in a 
vial containing 73 mg BL-8040 free base peptide (on dry basis).  
BL-8040 Placebo is formulated as a sterile and non-pyrogenic lyophilized powder in a vial 
containing 50 mg of mannitol.  
Both BL-8040 drug product and its matching placebo are manufactured in accordance with 
(cGMP) requirements by 
 
  
Reconstitution and administration instructions will be provided in a separate study manual.  
6.3.2  G-CSF 
G-CSF will be sourced from a commercial supplier. 
6.4 
PACKAGING AND LABELING OF STUDY MEDICATION 
 
 
 
 
6.5 
DISTRIBUTION AND SHIPMENT OF STUDY MEDICATION 
The investigational medicinal product will be packed and shipped in appropriate boxes. If, 
upon arrival at the clinical investigation site, study drug supplies appear to be damaged, the 
study monitor should be contacted immediately.  
Each shipment of study drug supplies for the study will be accompanied by a shipment form 
describing the contents of the shipment, product certificate of analysis, acknowledgement of 
receipt and other appropriate documentation. The shipment form will assist in maintaining 
current and accurate inventory records. The study staff will confirm the receipt of clinical 
supply by IWRS system. 
All study supplies should arrive at the Pharmacy/Investigational site in sufficient quantity and 
in time to enable dosing as scheduled. The Sponsor or its representative must notify the 
Principal Investigator’s designee prior to dispatch of drug supplies, with the anticipated date 
of their arrival.  

 
 
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6.6 
STORAGE, DISPENSING AND RETURN OF THE INVESTIGATIONAL MEDICINAL 
PRODUCT 
6.6.1 BL-8040 or Placebo 
Vials of BL-8040 for injection or its placebo should be stored in the refrigerator (2-8°C) in its 
original packaging, protected from light. 
Records should be kept by the Investigator or designee as to how much study drug was 
dispensed to each subject. The study monitors must periodically check the study drug 
supplied to ensure expiry date was not reached, sufficient amount of study drug is available, 
that drug accountability is being performed at each visit, and drug accountability logs are 
maintained.  
All investigational products must be kept in a secure area with access to the study drug 
limited to designated study personnel.  
Only trained personnel under the supervision of either the Investigator or the local pharmacist 
are authorized to dispense and administer study drug to participating subjects. Further details 
and instructions will be provided in the Pharmacy Manual. 
6.6.2 G-CSF (Filgrastim) 
Institutional guidelines for filgrastim will be followed for storage and dispensation. 
6.7 
ACCOUNTABILITY AND COMPLIANCE OF INVESTIGATIONAL MEDICINAL PRODUCT 
Each delivery must be acknowledged by the hospital pharmacist (or authorized study team 
member responsible for the investigational medicinal product). Accurate, complete and 
timely documentation of study drug distribution will be maintained by the pharmacy and the 
study staff of the investigational site, which may include confirmation of receipts of clinical 
supply, drug accountability logs and other forms.  
The medical center pharmacist (or authorized study team member responsible for the 
investigational medicinal product) is responsible for ensuring the supervision of the storage 
and allocation of these supplies, which will be forwarded to the Investigator at the 
appropriate time before administration. The Investigator may dispense investigational drug 
only to subjects enrolled in the study.  
Drug accountability records must be maintained by the clinical investigation site at all times. 
At the last study visit, all used and unused investigational drug will be collected and drug 
accountability performed by the study staff.  The study monitor will check these regularly 
during monitoring visits.  
The subject number, the date, batch number/kit number and quantity of study drug used by 
the subject will be checked for correctness and recorded on the appropriate accountability 
forms. Unused drug supplies will be returned to the Sponsor. At the end of the study, all 
clinical supplies and the corresponding accountability forms must be returned to the Sponsor, 
the study monitor, or designee for reconciliation or destruction. A photocopy of these records 
must be kept at the clinical investigation site. 
The inventory will be made available to the study monitor, who will verify accountability and 
verify dose during the course of the study. 

 
 
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Study drug orders, records of study drug receipts, dispensing records and inventory forms 
located at the site will be examined and reconciled by the study monitor periodically during 
and at the end of the study.   
6.8 
CONCOMITANT THERAPY 
If there is a clinical indication for any medication that is not part of the local standard of care 
and is specifically prohibited during the trial this should be discussed with the Sponsor’s 
Medical Monitor. The final decision on any supportive therapy or vaccination rests with the 
Investigator and/or the subject's primary physician. However, the decision to continue the 
subject’s trial therapy requires mutual agreement of the Investigator, the Sponsor, and the 
subject. 
The following washout periods prior to the first dose of G-CSF for mobilization are required 
for the following agents/medications. 
 Dexamethasone: 7 days 
 Thalidomide: 7 days 
 Lenalidomide: 7 days 
 Pamolidomide: 7 days 
 Bortezomib: 7 days 
 Ixazomib :7 days  
 Carfilzomib: 7 days 
 G-CSF: 14 days 
 GM-CSF or Neulasta®: 21 days 
 Combination/multi-agent cyto-reductive therapy: 7 days 
 Erythropoietin or erythrocyte stimulating agents: 30 days 
 Eltrombopag, romiplostim or platelet stimulating agents: 30 days 
 BCNU: 42 days/6 weeks 
 Daratumumab: 28 days  
 
There are no restrictions against any medications except post-transplantation chemotherapy 
for maintenance within the 60-days post-transplantation (unless patient is in documented 
relapse).  
6.8.1 Acceptable Concomitant Medications 
All treatments that the Investigator considers necessary for a subject’s welfare may be 
administered at the discretion of the Investigator in keeping with the community standards of 
medical care. If changes occur during the trial period, documentation of drug dosage, 
frequency, route, and date should also be included in the CRF. 
All medications and/or nutritional supplements/therapies taken by patients within 12 months 
prior to screening and for the duration of study participation will be recorded in the patients’ 
records and transcribed into the CRF as follows: documentation of concomitant medications 
will begin at screening. Subsequently, patients will be monitored for concomitant 
medications from the time of the first dose of G-CSF for mobilization until day of 
transplantation (Visit 10) inclusive. Concomitant medications taken during follow-up visits 
will be recorded only if myeloma drugs, G-CSF, erythropoietin, alternative stimulating agents 

 
 
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and/or transfusions were also given in that month prior to the visit, to identify any possible 
medications that may be associated with bone marrow suppression, graft dysfunction or 
relapse. 
Myeloma-related medication, G-CSF, erythropoietin, alternative stimulating agents and/or 
transfusions should be reported from the screening and up to 100 days post transplantation. 
 
Pre-Dose medication and general injection instructions: 
Premedication with an antihistamine is required for all patients, within one hour prior to 
study drug administration. The time of administration of premedication is to be recorded on 
site documentation and in the CRF. The preferred route for administration of premedication is 
IV. 
 The recommended premedication regimen is: H1 blocker (e.g diphenhydramine, 
Promethazine, etc) + H2 blocker (e.g. famotidine, ranitidine, etc) + leukotriene 
inhibitor (e.g. montelukast).  This triple-drug combination is required prior to the first 
dose of BL-8040 
 Analgesic medication may be added to the premedication regimen at the discretion of 
the treating physician. 
 BL-8040 is to be administered at a dose of 1.25 mg/kg by slow subcutaneous injection 
of at least 2 minutes per syringe.  If the volume to be administered exceeds 2 mL then 
the injection should be divided into two or more syringes to be administered at 
different injection locations.  
 Transient hypotension was witnessed in several cases following the initial treatment 
with BL-8040. Therefore, caution should be taken with the use of negative 
chronotropic drugs such as beta blockers. When appropriate, beta blocker should be 
replaced with non-negative chronotropic drugs. 
 All patients are to remain under surveillance for 2 hours after the first administration 
of BL-8040.  Patients receiving an additional dose of BL-8040, should remain under 
observation for 1 hour after the subsequent administration of BL-8040. 
 BL-8040 should only be administered when personnel and therapies are immediately 
available for the treatment of anaphylaxis and other hypersensitivity reactions, should 
they occur. 
6.8.2 Prohibited Concomitant Medications 
Subjects are prohibited from receiving the following therapies during the screening period 
and Treatment Phase of this trial: 
 Those listed previously in the exclusion criteria 
 Antineoplastic systemic chemotherapy or biological therapy 
 Chemotherapy not specified in this protocol 
 Investigational agents other than BL-8040 
 Radiation therapy: Radiation therapy to a solitary symptomatic lesion may be 
considered on an exceptional case by case basis after consultation with the Sponsor. 
 Maintenance treatment with lenalidomide, bortezomib, pomalidomide, thalidomide, 
carfilzomib, etc. within 60 days post-transplantation. 
 

 
 
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If there is a clinical indication for any medication specifically prohibited during the trial, 
approval should be discussed with the Sponsor Medical Monitor. Subjects may receive other 
medications that the Investigator deems to be medically necessary. There are no prohibited 
therapies after the 60 days post-transplantation during the Post-Treatment Follow-up Phase. 
7. 
SAFETY AND PHARMACOVIGILANCE 
7.1 
ADVERSE EVENT (AE) 
An AE is defined in ICH E6 as “any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have a causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product.” 
An abnormal result of diagnostic procedures, including abnormal laboratory findings, will be 
considered an AE if it fulfills one or more of the following:  
 Results in subject's withdrawal by the Investigator 
 Is associated with an SAE 
 Is associated with clinical signs or symptoms 
 Is considered by the physician to be of clinical significance 
 A new condition or the worsening of a pre-existing condition will be considered an 
AE.  
 
AEs do not include the following: 
 Post-transplantation neutropenia or thrombocytopenia  
 Medical/surgical procedures are not AEs (e.g., surgery, endoscopy, tooth extraction, 
transfusion). The condition that leads to the procedure is an AE if the procedure was 
not planned at screening visit. 
 Overdose of concomitant medication without any signs or symptoms unless the 
subject is hospitalized for observation.  
 Hospitalization for elective surgery planned prior to study (situation where an 
untoward medical occurrence has not occurred). 
 Disease progression 
 
All AEs, whether observed by the Investigator or designee or volunteered by or elicited from 
the subject, should be recorded individually on an AE CRF page with the following 
information: The specific event or condition, whether the event was present pre-baseline or 
not, the dates and times if available (using the 24 hour clock, where midnight is 00:00 and 
noon is 12:00) of occurrence, duration, severity, relationship to study medication, action 
taken to study drug, outcome, and whether considered non-serious or serious, drug-related or 
not.  
Once the subject has signed the Informed Consent Form (ICF), AEs will be recorded up to 30 
days from the last dose of study drug. The severity of the AE will be assessed by the 

 
 
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investigating physician in accordance with the definitions below. A Serious AE must fulfill 
the requirements listed in Section 7.2. 
AE will be recorded and graded according to the latest version of the NCI-CTCAE (currently 
version 5.0) (see Table 3) and coded into the database according to the latest version of 
MedDRA (currently version 20.1).  
Table 3: 
Severity of Adverse Events According to CTCAE (Version 5) 
 
Grade Description 
0 
No AE or within normal limits 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL) 
3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death related to AE 
A semi-colon indicates ‘or’ within the description of the grade. 
A single dash (-) indicates a grade is not available 
 
The following definitions should be used for toxicities/AEs that are not defined in the 
CTCAE: 
 Mild (Grade 1): The AE is noticeable to the subject but does not interfere with routine 
activity, no medical intervention is required.   
 Moderate (Grade 2): The AE interferes with routine activity but responds to 
symptomatic therapy or rest. 
 Severe (Grade 3): The AE significantly limits the subject’s ability to perform routine 
activities despite symptomatic therapy. 
 Life-threatening (Grade 4): The subject is at immediate risk of death. 
 
The Investigator will document his opinion of the relationship of the AE to treatment with 
investigational product using the criteria outlined in Table 2.  
Outcome to Date are classified as follows: 
 Recovered: The subject has fully recovered from the AE with no residual effects 
observable 
 Recovered with sequelae: The subject has recovered from the AE with residual effects 
observable 
 Improved: the subject status improved but has not been fully recovered 
 Ongoing: AE is not recovered 
 Fatal 
 Unknown 
 
AEs will be coded by Data Management using the latest version of MedDRA (
 
) AE dictionary. 

 
 
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All AEs, serious and not serious, will be recorded on the AE Case Report Form, and if 
relevant, the Concomitant Medications Record in the CRF will be updated. Severity and 
relationship to study drug will be assessed by the Investigator as described in Table 3.  
Particular attention should be made to ensure no discrepancies between the AE and the SAE 
form (i.e. outcome, severity, relationship must be consistent).   
Treatment-emergent AEs (TEAEs) are defined as AEs observed after 1st dose of study drug. 
Table 4: 
Relationship of Adverse Event to Treatment  
 
Term 
Definition 
Clarification 
No 
reasonable 
possibility 
(not related) 
 
This category applies to adverse 
events which, after careful 
consideration, are clearly due to 
extraneous causes (disease, 
environment, etc.) or to adverse 
events, which, after careful 
medical consideration at the time 
they are evaluated, are judged to 
be unrelated to the study drug. 
The relationship of an adverse event may be considered 
“no reasonable possibility” if it is clearly due to 
extraneous causes or if at least 2 of the following apply: 
• 
It does not follow a reasonable temporal sequence 
from the administration of the test drug. 
• 
It could readily have been produced by the patient’s 
clinical state, environmental or toxic factors, or 
other modes of therapy administered to the patient. 
• 
It does not follow a known pattern of response to 
the test drug.  
• 
It does not reappear or worsen when the drug is 
re-administered. 
Reasonable 
possibility 
(related) 
 
This category applies to adverse 
events for which, after careful 
medical consideration at the time 
they are evaluated, a connection 
with the test drug administration 
cannot be ruled out with 
certainty nor felt with a high 
degree of certainty to be related 
to the study drug. 
The relationship of an adverse event may be considered 
“reasonable possibility” if at least 2 of the following 
apply: 
• 
It follows a reasonable temporal sequence from 
administration of the drug. 
• 
It cannot be reasonably explained by the known 
characteristics of the patient’s clinical state, 
environmental or toxic factors, or other modes of 
therapy administered to the patient. 
• 
It disappears or decreases on cessation or reduction 
in dose. There are important exceptions when an 
adverse event does not disappear upon 
discontinuation of the drug, yet drug-relatedness 
clearly exists. 
• 
It follows a known pattern of response to the test 
drug. 
 
All resource use in the management of an AE will be collected.  
7.2 
SERIOUS ADVERSE EVENTS (SAES) 
An SAE is any AE occurring at any dose that suggests a significant hazard or side effect, 
regardless of the Investigator or Sponsor's opinion on the relationship to the investigational 
medicinal product and that results in, but may not be limited to, any of the following 
outcomes: 
 Death (regardless of the cause) 
 A life-threatening experience 
 In-patient hospitalization or prolongation of existing hospitalization (any in-patient 
hospital admission that includes a minimum of an overnight stay in a health care 
facility) 

 
 
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 A persistent or significant disability/incapacity 
 A congenital anomaly or birth defect 
 Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be serious when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed above. 
 
In-patient hospitalization or prolongation of existing hospitalization means that hospital 
in-patient admission and/or prolongation of hospital stay were required for treatment of AE, 
or that they occurred as a consequence of the event. 
Hospitalization for elective treatment of a pre-study condition (pre-baseline) that did not 
worsen while on study and optional hospitalizations not associated with a clinical AE (e.g. 
elective cosmetic surgery) are not considered SAEs.  
Significant medical events are those which may not be immediately life-threatening but may 
jeopardize the subject and may require intervention to prevent one of the other serious 
outcomes listed above. Examples of such events are intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result 
in hospitalization; such an AE will normally be considered serious by this criterion. 
A life-threatening adverse drug experience is any AE that places the subject, in the view of 
the Investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not 
include a reaction that, had it occurred in a more severe form, might have caused death.  
Any newly emergent SAEs, after treatment is discontinued or the subject has completed the 
study and is considered to be related to the study drug or study participation, should be 
recorded and reported immediately to Sponsor or delegate.   
All resource use in the management of an SAE will be collected.  
7.3 
DEFINITION OF AN UNEXPECTED ADVERSE EVENT 
An unexpected adverse drug event is any AE, the specificity or severity of which is not 
consistent with information in the current Investigator’s Brochure for an unapproved 
investigational product. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is a SAE assessed as 
unexpected by the Sponsor and that is judged by either the reporting Investigator or the 
Sponsor to have a reasonable causal relationship to the investigational medicinal product. 
7.4 
EXCEPTIONS IN THE REPORTING OF SAE 
According to EU and FDA detailed guidance on the collection, verification and presentation 
of adverse reaction reports arising from clinical trials on medicinal products for human use, 
regarding clinical trials in high morbidity or mortality diseases, it is acceptable to define 
some exceptions in the immediate reporting of specific SAEs. Refer to EU guidance 
ENTR/CT3, 5.1.9 and FDA guidance “Safety Reporting Requirements for INDs and BA/BE 
Studies” (Dec 2012). 
High dose chemotherapy is a recognized condition with a relatively high morbidity and/or 
high mortality. Under these circumstances, it seems appropriate that the SAEs, clearly related 
to the high dose chemotherapy could be an exception for an immediate systematic reporting. 

 
 
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These AEs will be thoroughly handled and followed up through the CRF (AE form) and will 
be reviewed monthly by the medical safety officer and could be re-qualified for reporting if 
necessary. 
Each event must be carefully analyzed by the Investigator’s designee to decide whether the 
SAE could be considered as an exception or must be immediately reported.  
7.5 
NOTIFICATION OF SERIOUS ADVERSE EVENT (SAE) 
Initial notification of SAEs 
An Initial SAE report form must be completed and sent to Pharmacovigilance within 24 
hours of the Investigator’s knowledge of the event. Any fatal or life-threatening event 
should be reported immediately, by phone, CRF, fax and/or email. Reporting SAEs to 
regulatory authorities and/or IRBs will comply with local regulations. 
Minimum Criteria for a Valid Initial SAE Case: 
For regulatory purposes, initial SAE reports should be submitted to the Sponsor’s Medical 
Monitor or designee immediately and should include: 
1. 
A suspected study drug (whether or not it is suspected to be related to one or 
both study drugs) 
2. 
An identifiable subject (e.g. study subject code number) 
3. 
An AE with the Investigator’s assessment of seriousness 
4. 
An identifiable reporting source (Investigator contact details) 
 
The Initial SAE report will be followed within 24 hours by a completed SAE report including 
a sufficiently-detailed narrative to allow for a medical assessment of the case, as well as 
copies of hospital case reports, results of applicable diagnostic tests, laboratory results, 
biopsy results, autopsy reports and other documents when requested and applicable. 
The Investigator must be prepared to supply the Sponsor with the following information: 
 Investigator Name and Center Number  
 Subject Number 
 Subject Initials 
 Subject Demographics 
 Clinical Event 
 Description 
 Date of onset 

 
 
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 Severity 
 Treatment (including hospitalization) 
 Relationship to study drug (causality) 
 Action taken regarding study drug 
 If the AE was Fatal or Life-threatening 
 Cause of death (whether or not the death was related to study drug). 
 Autopsy findings (if available). 
Once sent, the SAE form and accompanying documentation should be placed in the SAE 
section of the Investigator’s site file. 
 
Follow-up of SAEs:  
Follow-up of all SAEs that occur during the study will continue until their satisfactory 
resolution or stabilization. In outstanding cases, it may be defined as “ongoing without 
further follow-up” if mutually agreed by the Investigator and Sponsor. 
A Follow-up SAE Report Form must be completed by the site (marked as “Follow-up 
report”) and sent to the Pharmacovigilance department within a reasonable timeframe (an 
SAE Follow-up report is required whether or not there is any additional information to the 
initial report).   
The contact information for Follow-up SAE reporting is the same as for initial SAE reports 
(see above section).  
As for the initial SAE report, once sent, the Follow-up SAE report and accompanying 
documentation should be placed in the SAE section of the Investigator’s site file.  
7.6 
TIMEFRAME FOR REPORTING REQUIRED EVENTS  
For the time-period beginning at the signature of the consent form and ending at Baseline, 
any SAE that occurs to any subject, and any follow-up to an SAE, including death due to any 
cause, must be reported within 24 hours to the Sponsor if it causes the subject to be excluded 
from the trial, or is the result of a protocol-specified intervention, including but not limited to, 
washout or discontinuation of usual therapy, diet or a study procedure. 
For the time period beginning at Screening and up to 30 days after the last dose of study drug, 
any SAE, or follow-up to an SAE, including death due to any cause, whether or not related to 
the Sponsor's product, must be reported within 24 hours to the Sponsor either by electronic 
media or paper. 
Additionally, any SAE considered by an Investigator who is a qualified physician to be 
related to the Sponsor's product that is brought to the attention of the Investigator at any time 
and up to 30 days following the last dose of study drug must be reported immediately to the 
Sponsor. 
All subjects with SAEs must be followed up for outcomes. 

 
 
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8. 
STATISTICAL METHODOLOGY 
8.1 
GENERAL 
This Phase III study was designed to meet two sequential goals. In Part 1 of the study, a total 
of up to 30 subjects will be enrolled to an open-labeled treatment with G-CSF followed by 
BL-8040 1.25 mg/kg with the aim of ensuring that 1.25 mg/kg is the optimal BL-8040 dose. 
This part will be conducted in 3 sequential steps of 10 subjects each and the accumulated data 
at each step will be reviewed by an independent DMC. 
Following the successful completion of Part 1, a total of 177 subjects will be randomized into 
Part 2 of the study which will employ a randomized, double-blinded, placebo-controlled 
design to assess the safety, tolerability and efficacy of BL-8040 + G-CSF as compared to 
Placebo + G-CSF. 
One interim analysis for potential early termination of new subject recruitment into the study 
will be conducted at the time when a total of 65% of the planned sample size will be 
randomized and have completed the stem cell mobilization procedure. 
8.2 
RANDOMIZATION 
Following the successful completion of Part 1, subjects will be randomized using a 2:1 ratio 
to receive BL-8040 + G-CSF or Placebo + G-CSF, respectively. Randomization will use 
permuted blocks stratifying subjects by remission status (CR or PR) and baseline platelet 
count (<200 x 109/L or ≥200 x 109/L). 
8.3 
INTERIM ANALYSIS, TYPE-I ERROR AND MULTIPLICITY ADJUSTMENT 
The overall alpha level for this study is 0.05 using 2-tailed tests. All significance testing for 
this study will use two-tailed tests. 
One interim analysis for potential early termination of new subject recruitment into the study 
will be conducted at the time when a total of 65% of the planned sample size will be 
randomized and have completed the stem cell mobilization procedure. 
For the interim analysis, treatment effect will be considered statistically significant if the 
p-value will be 
 or less. As the interim analysis will be conducted only for potential 
early termination of new subject recruitment into the study, the final analysis of primary and 
secondary endpoints, which will be conducted at the Core Study Termination Visit (Visit 13) 
that will occur at Day 100 following transplantation (or early terminated before), will require 
a p-value of 
. These p-values represent the use of the Lan-DeMets’ correction to 
type-I error. 
Furthermore, one (1) primary endpoint and 2 secondary endpoints are pre-defined for this 
study. Hence, there will be a total of 3 comparisons for the primary and secondary endpoints 
altogether. The hierarchical method for multiple endpoint testing for the secondary endpoints 
will utilize the gate keeping approach at alpha=
, ensuring that the overall 
experiment-wise type-I error of 5% is preserved. 

 
 
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The hierarchical order of primary and secondary endpoints testing will be as outlined below: 
1. Primary endpoint: Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up 
to 2 apheresis sessions in preparation for auto-HCT after single administration of BL-
8040 + G-CSF or placebo + G-CSF. 
2. Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session.  
3. Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session.  
8.4 
SAMPLE SIZE JUSTIFICATION 
Altogether, a total of up to 207 subjects will be enrolled into the study, as detailed hereafter. 
8.4.1 Sample Size Justification for Part 1 (Open labeled period for ascertaining the 
BL-8040 dose optimization) 
To ascertain the dose of BL-8040, a total of up to 30 subjects will be enrolled to Part 1 of the 
study. The population size of Part 1 was determined based on the following assumptions:   
 The endpoint to be used in order to ascertain the BL-8040 dose will be the proportion 
(%) of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions in 
preparation for auto-HCT after G-CSF + single administration of BL-8040. 
 It is assumed that the proportion (%) of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg 
with up to 2 apheresis sessions due to treatment with BL-8040 + G-CSF will be 70% or 
more.  
 Based on DiPersio et al20, it is assumed that the null reference hypothesis to be 
overcome is 35.3%. 
 
 
 for one binomial proportion at a two-sided alpha level of 5%, 
we determined that a total of 24 subjects will provide 95% power to demonstrate superiority 
over the reference value of 35.3%. To account for potential dropouts, the Part 1 population 
size is further increased to a total of 30 subjects.  
8.4.2 Sample Size Justification for Part 2 (Randomized, Placebo-Controlled Part) 
The power and the derived sample size for Part 2 of the study were calculated based on the 
following assumptions: 
 The primary study endpoint is the proportion (%) of subjects mobilizing ≥6.0 x 106 
CD34+ cells/kg with up to 2 apheresis sessions in preparation for auto-HCT after G-
CSF + single administration of BL-8040 or Placebo + G-CSF. 
 Subjects will be randomized to treatment with BL-8040 + G-CSF or to Placebo + G-
CSF using a 2:1 randomization ratio, respectively. 
 It is assumed that success rates for mobilizing ≥6 x 106 cells/kg in MM subjects 
following treatment with Placebo + G-CSF will be 35%. 
 It is also expected that treatment with BL-8040 will result in a success rate of 70%, in 
line with results obtained for subjects treated with Mozobil + G-CSF. However, as a 
worst-case scenario, it is assumed that 20% of subjects assigned to the BL-8040 + 
G-CSF group would not get their assigned treatment and therefore, using the intention-
to-treat (ITT) principle, this would reduce the BL-8040 success rate to 63%. 

 
 
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 An additional attrition rate of 20% has also been taken into consideration. 
 Final analysis will employ an alpha level of 
. 
 SAS® PROC POWER for two proportions was used to determine the sample size.    
 
According to the above underlying assumptions, a total of 177 subjects will provide 89.8% 
power to demonstrate that treatment with BL-8040 + G-CSF is superior, at a two-sided alpha 
of 
, to treatment with Placebo + G-CSF in the study primary endpoint. 
The power at interim analysis, assuming an attrition rate of 20% and success rates of 70% 
and 35% for BL-8040 + G-CSF or Placebo + G-CSF, respectively, is 85.9%. 
8.5 
DATA ANALYSES SETS 
The following data analysis sets are defined for the analyses of the data accumulated during 
the conduct of Part 2 of the study: 
• 
Intention-to-Treat Analysis Set (ITT): In accordance with the intention-to-treat 
principle, all randomized participants will be included in the ITT analysis set according 
to the treatment group to which they were originally randomized. The Intention-to-Treat 
(ITT) analysis set will serve as the principal analysis set for efficacy assessments. 
• 
Modified Intention-to-Treat Analysis Set (mITT): The mITT analyses set will consist 
of all randomized subjects who were treated with the study drug and had at least one 
post-Baseline efficacy assessment according to the treatment group to which they were 
originally randomized.  
• 
Per Protocol Analysis Set (PP): The per-protocol analysis set (PP) will consist of all 
randomized subjects who were treated with study drug according to protocol guidelines 
without any major protocol violations. Analyses will be conducted according to 
treatment actually administered. 
• 
Safety Analysis Set (ST): The safety analysis set (ST) will consist of all subjects who 
have been randomized and received at least one dose of study\drug according to 
treatment actually administered. The safety analysis set (ST) will serve as the principal 
analysis set for safety assessments. 
 
In addition, the following data analysis set is defined for the analyses of the adverse event 
data accumulated during the conduct of both Part 1 and Part 2 of the study: 
• 
Study Part 1 and Part 2 Analysis Set (P1P2): The P1P2 analyses set will consist of all 
subjects who were treated with the study drug during Part 1 and Part 2 of the study and 
had at least one post-Baseline assessment according to the treatment actually 
administered.  
 
8.6 
SEQUENCE OF PLANNED ANALYSES 
Study enrollment may be terminated early in the case that interim analysis will provide 
statistically significant (p<
) evidence favoring treatment with BL-8040 + G-CSF. 
Otherwise, study will continue to randomize up to 177 subjects. 

 
 
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The sequence of the planned statistical analyses for this study is described below in the 
planned chronological order:  
• 
Initially, the interim analysis will be conducted at the time when a total of 65% of the 
planned study population will be randomized and have completed the stem cell 
mobilization procedure. The results obtained for this analysis will be used only to 
determine if study enrollment is to be halted. 
• 
Thereafter, the core set of the study accumulated data will be made available for 
statistical analyses on the day that the last study randomized subject completes the Core 
Study Termination Visit (Visit 13), which will occur at his/her Day 100 following 
transplantation (or early terminated before). At that time the study database will be 
locked and a formal statistical analysis of the following endpoints will be conducted: 
 Primary Endpoint: Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with 
up to 2 apheresis sessions in preparation for auto-HCT after single administration of 
BL-8040 + G-CSF or placebo + G-CSF. 
 Secondary Endpoint: Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 
1 apheresis session.  
 Secondary Endpoint: Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 
1 apheresis session.  
 Additional Secondary Endpoint: Time to neutrophil engraftment, defined as ANC 
≥0.5 x 109/L for 3 consecutive days or ≥1.0 x 109/L for 1 day following the 
conditioning regimen associated nadir.  
 Additional Secondary Endpoint: Time to platelet engraftment, defined as the first of 3 
consecutive measurements of platelet count ≥20 x 109/L without platelet transfusion 
support for 7 days following the conditioning regimen associated nadir. 
 Additional Secondary Endpoint: Time to engraftment defined as the time to 
neutrophils and platelets engraftment whichever comes later. 
 Additional Secondary Endpoint: Graft durability at 60 days post-transplantation - only 
in case of patients in whom maintenance therapy will be given around Day 60.  
 Additional Secondary Endpoint: Graft durability at 100 days post-transplantation. 
 Economic endpoint: Resource use and cost up until engraftment, 100 days after 
transplantation. 
 Exploratory Endpoint: Change from Baseline in peripheral blood CD34+ cell 
concentration on apheresis Day 1 or Day 1 and 2, if applicable, after BL-8040/placebo 
single administration. 
 Exploratory Endpoint: Mobilization of Myeloma cells assessed in the apheresis 
product after BL-8040/placebo administration. 
 Exploratory endpoint: To descriptively compare the CD34+ cells collected per kg of 
actual body weight (ABW) used in this study to the theoretical amount of CD34+ 
cells collected based on ideal body weight (IBW) 
 
The results and conclusions obtained from the integrative assessment of these efficacy 
endpoints, as well as accumulated safety data up to this cut-off date, will be summarized 
in a Clinical Study Report (CSR) in support of regulatory approval of BL-8040 + G-CSF 
for the treatment of Multiple Myeloma. 
BioLineRx believes that unblinding the study following the day that the last randomized 
subject completes the Core Study Termination Visit, which will occur at his/her Day 100 

 
 
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following transplantation, will not compromise study integrity and blinding and thus will 
not be associated with any bias for the subsequent sequence of the planned analyses due 
to the following reasons: 
 Study recruitment, randomization and administration of study IP will already be 
completed at this study stage. 
 Long-term graft durability endpoints are based on objective measures and therefore 
are not likely to be influenced by treatment allocation. 
 The individual subject treatment assignment and data listings will only be shared with 
the Sponsor’s dedicated taskforce and with regulatory authorities.  
 The publicly disseminated information will be on a by “group basis”.  
 The observed summary statistics of efficacy outcomes will not allow determining 
individual subject assignment.  
 The observed summary statistics of adverse events will not allow determining 
individual subject assignment. 
 
The third set of study accumulated data will be made available for statistical analyses of 
the long-term graft durability endpoints, as well as the longer-term safety data, on the 
day the last randomized subject completes Visit 16, which will occur at 12 months 
following transplantation. At that time the study database will be locked again, and a 
formal statistical analysis of the following endpoints will be conducted: 
 Additional Secondary Endpoint: Graft durability at 6 months post-transplantation. 
 Additional Secondary Endpoint: Graft durability at 12 months post-transplantation. 
 Exploratory Endpoint: Proportion of subjects with graft failure post-transplantation.  
 
The results and conclusions obtained from the integrative assessment of these secondary 
efficacy endpoints, as well as accumulated safety data up to this cut-off date, will be 
summarized in a supplement to the CSR in further support of regulatory approval of BL-
8040 + G-CSF for the treatment of Multiple Myeloma. 
• 
The last set of study accumulated data will be made available for statistical analyses of 
the long-term exploratory endpoints at 5 years following the randomization of the last 
study subject. At that time, the entire study will be terminated, the study database will be 
locked again, and a formal statistical analysis of the following endpoints will be 
conducted: 
 Exploratory Endpoint: Overall Survival (OS) during the period of up to 5 years. 
 Exploratory Endpoint: Relapse-Free Survival (RFS) during the period of up to 5 
years. 
 
The results and conclusions obtained from the integrative assessment of these 
exploratory efficacy endpoints will be summarized in an additional supplement to the 
CSR in further support of the regulatory approval of BL-8040 + G-CSF for the treatment 
of Multiple Myeloma. 
8.7 
INTERIM ANALYSES 
An interim analysis for the primary endpoint only will be conducted for potential early 
termination of new subject recruitment into the study as described above.  

 
 
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8.8 
EFFICACY ENDPOINTS AND ANALYSES 
All efficacy endpoints will be tested for the ITT analysis set controlling for multiplicity as 
outlined in Section 8.3. 
8.8.1 Primary Efficacy Endpoint and Principal Statistical Analysis 
The primary study endpoint is the proportion (%) of subjects mobilizing ≥6.0x106 CD34+ 
cells/kg with up to 2 apheresis sessions in preparation for auto-HCT after G-CSF + single 
administration of BL-8040 or Placebo + G-CSF. 
The following rules will be incorporated to derive this endpoint: 
• 
Only subjects randomized to study treatment during Part 2 of the study will be included 
in the formal efficacy analysis. 
• 
A subject who cumulatively mobilizes ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis 
sessions will be classified as a “Responder”. 
• 
Other subjects, including randomized subjects who failed to complete the stem cell 
mobilization procedure, as well as those who did not mobilize 6.0 x 106 CD34+ cells/kg 
after up to 2 apheresis sessions, will be classified as “Non-Responders”. 
 
The principle analysis of this binary endpoint will use the Cochran-Mantel-Haenszel test 
stratified by remission status (CR or PR) and baseline platelet count (<200 x 109/L or 
≥200 x 109/L). 
In addition, the number and proportion of subjects meeting this endpoint will be displayed by 
treatment group. 
8.8.1.1 Sensitivity Analyses for the Principal Analysis of the Primary Endpoint 
The robustness of the results of the principal analysis of the primary endpoint will be 
explored employing the following: 
• 
Primary Sensitivity Analysis Using Logistic Regression: 
The primary sensitivity analysis of this binary end-point will be based on estimating a 
contrast (BL-8040 + G-CSF vs. Placebo + G-CSF) derived from a baseline-adjusted, 
Logistic Regression model [
 
 
] to this binary outcome measure. In addition to the treatment group, the 
model will include the following covariates: remission status (CR or PR) and baseline 
platelet count (<200 x 109/L or ≥200 x 109/L). 
The treatment effect (odds-ratio) of BL-8040 + G-CSF vs. Placebo + G-CSF on the 
corresponding adjusted proportions will be displayed 
• 
Sensitivity Analysis Accounting for Missing Values: 
The ITT analysis set will be used for the below sensitivity analysis. To evaluate the 
possible impact of missing values on the principal analysis of the primary endpoint 
results assuming all missing data are Missing Not At Random (MNAR), a total of 
additional 4 sensitivity analyses using the primary analysis statistical model, will be 
conducted: 

 
 
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 The first analysis will consider randomized patients with missing data as 
“Responders”. 
 The second analysis will consider randomized patients with missing data as 
“Non-Responders”. 
 The third analysis will consider BL-8040+G-CSF randomized patients with missing 
data as “Non-Responders” and BL-8040+Placebo randomized patients with missing 
data as “Responders”. 
 The fourth analysis will consider BL-8040+G-CSF randomized patients with missing 
data as “Responders” and BL-8040+Placebo randomized patients with missing data 
as “Non-Responders”. 
• 
Other Sensitivity Analyses  
Other sensitivity analyses will be defined in the SAP. 
 
8.8.2 Secondary Efficacy Endpoints and Statistical Analysis 
Secondary endpoints will be tested for the ITT analysis set controlling for multiplicity using 
the hierarchical gate keeping method for multiple endpoints testing for the secondary 
endpoints. Study secondary endpoints will be tested using the gatekeeping principle as 
defined above in the following order: 
8.8.2.1 Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis 
session 
The following rules will be incorporated to derive this endpoint: 
• 
Only subjects randomized to study treatment during Part 2 of the study will be included 
in the analysis. 
• 
A subject who collects ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session in preparation 
for autologous hematopoietic cell transplantation (auto-HCT) will be classified as a 
“Responder”. 
• 
Other subjects, including randomized subjects who failed to complete the stem cell 
mobilization procedure, as well as those who did not mobilize 2.0 x 106 CD34+ cells/kg 
in 1 apheresis session, will be classified as “Non-Responders”. 
 
The analysis of this binary endpoint will use the Cochran-Mantel-Haenszel test stratified by 
remission status (CR or PR) and baseline platelet count (<200x109/L or ≥200x109/L). 
Sensitive analysis of this binary endpoint will be based on estimating a contrast (BL-8040 + 
G-CSF vs. Placebo + G-CSF) derived from a baseline-adjusted, Logistic Regression model 
[
 
] to this binary outcome 
measure. In addition to the treatment group, the model will include the following covariates: 
remission status (CR or PR) and baseline platelet count (<200 x 109/L or ≥200 x 109/L). 
The treatment effect (odds-ratio) of BL-8040 + G-CSF vs. Placebo + G-CSF on the 
corresponding adjusted proportions will be displayed. 
In addition, the number and proportion of subjects meeting this endpoint will be displayed by 
treatment group. 

 
 
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8.8.2.2 Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis 
session 
The following rules will be incorporated to derive this endpoint: 
• 
Only subjects randomized to study treatment during Part 2 of the study will be included 
in the analysis. 
• 
A subject who mobilizes ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session in preparation 
for autologous hematopoietic cell transplantation (auto-HCT) will be classified as a 
“Responder”. 
• 
Other subjects, including randomized subjects who failed to complete the stem cell 
mobilization procedure, as well as those who did not mobilize 6.0 x 106 CD34+ cells/kg 
in 1 apheresis session, will be classified as “Non-Responders”. 
 
The analysis of this binary endpoint will be based on estimating a contrast (BL-8040 + G-
CSF vs. Placebo + G-CSF) derived from a baseline-adjusted, Logistic Regression model 
 
] to this binary outcome 
measure. In addition to the treatment group, the model will include the following covariates: 
remission status (CR or PR) and baseline platelet count (<200 x 109/L or ≥200 x 109/L). 
The treatment effect (odds-ratio) of BL-8040 + G-CSF vs. Placebo + G-CSF on the 
corresponding adjusted proportions will be displayed. 
In addition, the number and proportion of subjects meeting this endpoint will be displayed by 
treatment group. 
8.8.3 Additional Secondary Efficacy Endpoints and Between Study Groups 
Descriptive Comparability Assessment 
For the comparability between the effects of BL-8040 + G-CSF versus placebo + G-CSF the 
below endpoints will be assessed in a descriptive manner: 
8.8.3.1 Time from transplantation to neutrophil engraftment, defined as ANC ≥0.5 x 
109/L for 3 consecutive days or ≥1.0 x 109/L for 1 day following the conditioning 
regimen associated nadir 
This endpoint will be presented using a Kaplan-Meier plot stratified by study group. Any 
estimate quoted from the Kaplan-Meier plot will have the estimate and the standard error 
(SE) of the estimate provided.  Greenwood’s formula will be used to calculate the SE. 
8.8.3.2 Time from transplantation to platelet engraftment, defined as the first of 3 
consecutive measurements of platelet count ≥20 x 109/L without platelet 
transfusion support for 7 days following the conditioning regimen associated 
nadir 
This endpoint will be presented using a Kaplan-Meier plot stratified by study group. Any 
estimate quoted from the Kaplan-Meier plot will have the estimate and the standard error 
(SE) of the estimate provided.  Greenwood’s formula will be used to calculate the SE. 

 
 
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8.8.3.3 Time from transplantation to engraftment defined as the time to neutrophils 
and platelets engraftment whichever comes later. 
This endpoint will be presented using a Kaplan-Meier plot stratified by study group. Any 
estimate quoted from the Kaplan-Meier plot will have the estimate and the standard error 
(SE) of the estimate provided.  Greenwood’s formula will be used to calculate the SE. 
8.8.3.4 Graft durability at 60 days post-transplantation.  
The number and proportion of subjects meeting this endpoint will be provided by treatment 
group and the odds-ratio of BL-8040 + G-CSF vs. Placebo + G-CSF on the corresponding 
proportions will be displayed. 
8.8.3.5 Graft durability at 100 days post-transplantation.  
The number and proportion of subjects meeting this endpoint will be provided by treatment 
group and the odds-ratio of BL-8040 + G-CSF vs. Placebo + G-CSF on the corresponding 
proportions will be displayed. 
8.8.3.6 Graft durability at 6 months post-transplantation 
The number and proportion of subjects meeting this endpoint will be provided by treatment 
group and the odds-ratio of BL-8040 + G-CSF vs. Placebo + G-CSF on the corresponding 
proportions will be displayed. 
8.8.3.7 Graft durability at 12 months post-transplantation. 
The number and proportion of subjects meeting this endpoint will be provided by treatment 
group and the odds-ratio of BL-8040 + G-CSF vs. Placebo + G-CSF on the corresponding 
proportions will be displayed. 
8.8.3.8 Pharmacoeconomic endpoint 
The resource utilization up until engraftment, 100 days after transplantation, multiplied with 
per country unit costs to obtain an average cost per patient per treatment arm. 
8.8.4 Exploratory Endpoints 
Analyses of the exploratory endpoints will provide additional insight into the therapeutic 
effect of BL-8040 + G-CSF as compared to Placebo + G-CSF. These endpoints will be tested 
for the ITT analysis set using the nominal alpha level of 5% without controlling for 
multiplicity. Detailed statistical methodology to be used for the analyses of these exploratory 
endpoints will be provided in a more detailed SAP to be developed while the study is ongoing 
and prior to locking the database and unblinding. The exploratory endpoints to be analyzed 
are: 
• 
Change from baseline in peripheral blood CD34+ cells concentration on apheresis Day 1 
or Day 1 and Day 2, if applicable, after BL-8040/placebo single administration. 
• 
Proportion of subjects with graft failure post-transplantation.  
• 
Overall Survival (OS) during the period of up to 5 years. 
• 
Relapse-Free Survival (RFS) during the period of up to 5 years. 
• 
Mobilization of Multiple Myeloma cells assessed in the apheresis product. 
• 
CD34+ cells collected per kg of actual body weight (ABW) compared to theoretical 
amount of cells collected based on ideal body weight (IBW). 

 
 
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8.9 
SAFETY AND TOLERABILITY ANALYSES 
Safety analyses will be performed for the Safety Analysis Set (ST) and for the Study Part 1 
and Part 2 Analysis Set (P1P2). 
8.9.1 Adverse Events 
An adverse event (AE) is defined in ICH E6 as “any untoward medical occurrence in a 
patient or clinical investigation subject administered a pharmaceutical product and which 
does not necessarily have a causal relationship with this treatment. An AE can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or 
disease temporally associated with the use of a medicinal (investigational) product, whether 
or not related to the medicinal (investigational) product.” The MedDRA dictionary will be 
used to standardize the terms used by the investigator to describe the Adverse Events (AEs). 
Adverse events will be recorded from the time a subject has signed the Informed Consent 
Form. Adverse events analyses will include only the Treatment Emergent Adverse Events 
(TEAEs), namely, those events which started at the time of first study IP administration or 
afterwards. The following analyses are pre-planned for adverse events: 
• 
The incidence (no. of patients) and frequency (no. of events) of most frequent TEAEs 
(>5%) by Preferred Term (PT). 
• 
The incidence (no. of patients) and frequency (no. of events) of TEAEs broken down by 
System Organ Class (SOC) and PT. 
• 
The incidence (no. of patients) and frequency (no. of events) of TEAEs broken down by 
SOC, High Level Term (HLT) and PT. 
• 
The incidence (no. of patients) and frequency (no. of events) of TEAEs by SOC and PT 
in Subjects Early Discontinued from Study/Treatment. 
• 
The incidence (no. of patients) and frequency (no. of events) of serious TEAEs by SOC 
and PT. 
• 
The incidence (no. of patients) and frequency (no. of events) of serious TEAEs by SOC, 
HLT and PT. 
• 
The incidence (no. of patients) and frequency (no. of events) of TEAEs when broken 
down by severity. 
• 
The incidence (no. of patients) and frequency (no. of events) of TEAEs broken down by 
relationship to study IP. 
• 
The incidence (no. of patients) and frequency (no. of events) of TEAEs when broken 
down by action taken with study IP.  
• 
The incidence (no. of patients) and frequency (no. of events) of TEAEs when broken 
down by event outcome. 
The Adverse Events dictionary used to code Investigator’s verbatim terms will be provided. 
Individual subject listings of all SAEs, treatment-emergent SAEs, TEAEs and non-TEAEs 
will be provided. 
8.9.2 Safety Laboratory Data 
Analyses of safety central laboratory data will be performed in the following manner: 
• 
Quantitative laboratory measurements will be categorized with reference to the normal 
ranges as Low, Normal or High. The incidence (no. of subjects) of abnormal values at 

 
 
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any time post initiation of the 1st study IP administration, calculated for subjects with 
normal values at Baseline will be provided. Analysis will include, per tested parameter, 
those subjects with normal baseline and at least one post-treatment measurement. A 
summary table will display the number and relative percentage of subjects with at least 
one abnormal value (above upper or below the lower normal range) at any time post-
initiation of the 1st study IP administration. 
• 
Quantitative laboratory measurements will be categorized with reference to the normal 
ranges as Low, Normal or High. Shift analysis of the categorical change from Baseline to 
each scheduled visit and to the last observed value will be provided. 
• 
Box-Plots of measurements done and figures of mean values ±SEs, as well as descriptive 
statistics for all laboratory quantitative parameters and changes from Baseline, will be 
provided by scheduled visits.  
8.9.3 Vital Signs 
Analyses of vital signs data will be performed in the following manner: 
• 
The more detailed SAP will provide the quantitative criteria used to define the 
potentially clinically significant (PCS) abnormal vital signs values. Measurements to be 
used in the analysis are those taken immediately following the first administration of the 
study IP and onwards. The incidence tables of PCS values as well as the individual 
subject listing will be provided. The denominator to be used for calculating percentages 
is the number of subjects with at least one observation post 1st study IP administration. 
• 
Box-Plots of measurements done, figures of mean values ±SEs, as well as descriptive 
statistics for all parameters and changes from Baseline (derived), will be provided by 
scheduled visits and treatment groups.  
8.9.4 Physical Examinations 
Analyses of physical examinations will be performed in the following manner: 
• 
Distribution of number of subjects by body system examined and result assessments 
made will be presented at Baseline and at Termination Visit. 
• 
Shift analysis of categorical change by body system will also be performed. 
• 
Incidence and listings of individual subject’s findings of Abnormal Clinically Significant 
following 1st study IP administration and onwards will also be provided. 
8.9.5 12-Lead ECG 
12-lead ECG will be recorded at Screening, Baseline and triplicate ECG on Day 4 prior to 
dosing and 30-45 min after study drug and on Day 5 prior to apheresis. If a second dose of 
study drug is provided, another triplicate ECG assessment will be performed on Day 6 pre-
dose and 30-45 min post dosea and prior to third apheresis. Additional ECGs may be 
performed at the discretion of the Investigator. Analyses of ECG evaluations will be 
presented in the report in the following manner: 
• 
Descriptive statistics and Box-Plots of quantitative 12-Lead ECG parameters measured 
by scheduled timepoints (Pre-Dose/Post-Dose) as well as their changes from Baseline. 
 
a Post dose defined as end time of administration  

 
 
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9. 
ETHICS 
9.1 
INSTITUTIONAL REVIEW BOARD (IRB) OR INDEPENDENT ETHICS COMMITTEE 
(IEC) 
Prior to initiation of the study, the Investigator will submit the study protocol and 
amendments, IB and amendments, ICF and any other documents that may be provided to the 
subject or any other documents requested by the IRB/IEC for review and approval. 
The names and affiliations of all members of the IRB/IEC must be provided to the PI and 
BioLineRx. In lieu of this, the IRB/IEC must certify that it has been officially 
authorized/recognized according to the national legislation. 
The IRB/IEC must provide written approval of the study to keep in the Investigator’s file. 
Records of approval of all documents pertaining to this study, including the local Regulatory 
Authority, should be filed as such. The Investigator will not begin the study until the 
protocol, ICF and any other document provided to the subject have been approved by the 
IRB/IEC. The Investigator must agree to make any required progress reports to the IRB/IEC, 
as well as reports of SAEs, life-threatening conditions or death. The IRB/IEC will also be 
notified of Part 1 preliminary results. 
9.2 
ETHICAL CONDUCT OF THE STUDY 
All clinical work conducted under this protocol is subject to ICH GCP E6 (R2) guidelines. 
This includes an inspection by Sponsor or its designee, Health Authority or IRB/IEC 
representatives at any time. The Investigator must agree to the inspection of study-related 
records by Health Authority representatives and/or Sponsor or its designee.  
The study will be conducted in accordance with Sponsor and/or designee’s standards 
operating procedures and the following guidelines: 
 GCP: Guideline for Good Clinical Practice ICH E6(R2)- ICH Harmonized Guideline 
Integrated Addendum to ICH E6 (R1) (International Conference on Harmonization of 
Technical Requirements for the Registration of Pharmaceuticals for Human Use), Step 
5, 14 June 2017 
 Declaration of Helsinki: Seoul, 2008 
 US Code of Federal Regulations (Title 21, CFR Part 11, 50, 54, 56 and 312) and/or 
EU Directives; and/or local country regulations and guidelines.  
9.3 
SUBJECT INFORMATION AND CONSENT 
Prior to screening for the study, each subject will be informed in detail about the study drugs 
to be administered and the nature of the clinical investigation with its risks and discomforts to 
be expected. The basic elements of informed consent as specified by the FDA (21 CFR 
50.25) and ICH-GCP will be followed. The subjects will also be instructed that they are free 
to withdraw their consent and discontinue their participation in the study at any time without 
prejudice. Written consent will be obtained from each subject to be involved in the clinical 
trial or his/her designated power of attorney (POA) by using the IRB/IEC-approved ICF prior 
to the conduct of any study-related activity. A copy of the ICF will be submitted together 
with this protocol and must be approved by the IRB/IEC prior to study commencement. Each 
subject will be given a copy of the written ICF, and each subject’s chart will include the 
signed ICF for study participation. The original subject signed and dated ICFs will be 

 
 
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maintained per ICH record retention requirements. Regulatory authorities may check the 
existence of the signed ICF in this central study folder if not having performed so during the 
study.   
9.4 
SUBJECT INSURANCE 
A product liability to cover against injury and damages arising from the use of investigational 
products in this project is provided by the Sponsor for the total duration of the study, 
covering the subjects and Investigators in respect of the risks involved in conducting this 
study according to this protocol. The insurance policy will be filed in the Investigator’s site 
file or can be made available to the Investigator and to the IRB/IEC upon request. 
Subjects will be insured through contract between an insurance company and the Sponsor. 
9.5 
INFORMING THE GENERAL PRACTITIONER 
When required by location regulation, the Investigator will inform the subject's primary care 
physician of his/her participation in the study, by sending a letter to the physician. 
9.6 
PERSONAL DATA PROTECTION 
The Sponsor will comply with local regulations and with the principle of subject’s right to 
protection against invasion of privacy. Throughout this trial, all subject data will be identified 
only by a subject identification number and subject initials and date of birth. The data will be 
blinded in all data analyses. The subject must be informed and consent to authorized 
personnel of the Sponsor, such as study monitor, auditor, etc. and relevant health regulatory 
agencies having direct access to personal medical data to assure a high-quality standard of the 
study. At the subject's request, medical information may be given to his or her personal 
physician or other appropriate medical personnel responsible for his or her welfare.   
9.7 
DATA AND SAFETY MONITORING  
An independent DMC will be responsible for periodically reviewing safety data 
collected during the study. Details with regard to DMC activities will be provided with the 
DMC Charter. 
Please refer to the Operations Manual for list of DMC members. 
9.8 
PROTOCOL EXCEPTIONS AND DEVIATIONS 
No prospective waivers will be allowed for patients who do not fulfill the inclusion/exclusion 
criteria. Deviations from the protocol should be avoided, unless required for the safety of the 
subject. Major Protocol deviations, and, if possible, the reason for occurrence, will be 
documented by the study monitor for visit reports and will be included in the final clinical 
study report. The Investigator must report any protocol deviations to the Sponsor or the 
Sponsor's designee, should they occur. If required, the Investigator should also report 
deviations to the IRB/IEC in accordance with local regulations and within a reasonable time.  
9.9 
PROTOCOL AMENDMENTS 
Changes to the protocol may be made only by the Sponsor (with or without consultation with 
the Investigator). All protocol modifications must be submitted to the site IRB/IEC in 
accordance with local requirements and, if required, to the Regulatory Authority, either as an 

 
 
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amendment or a notification. Approval for amendments must be received before any changes 
can be implemented, except for changes necessary to eliminate an immediate hazard to trial 
subjects, or when the changes involve only logistical or administrative aspects of the trial. No 
approval is required for notifications. 
10. 
QUALITY CONTROL AND QUALITY ASSURANCE  
The study will be conducted according to GCP as outlined by ICH Topic E6 (R2) Step 5 
guidelines. The CRO’s Standard Operating Procedures (SOPs) will be followed to ensure that 
clinical trials are conducted and data are generated, documented and reported in compliance 
with the protocol, GCP and applicable regulatory requirements. 
10.1 
AUDITS AND INSPECTIONS 
The study may be audited according to the Sponsor's or its designee's QA inspection 
program. The purpose of the audit is to determine whether or not the study is being conducted 
and monitored in compliance with the study protocol and ICH GCP guidelines. Audit visit(s) 
will be arranged in advance with site personnel at a mutually acceptable time. 
The Investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from the Sponsor or its designees or the 
regulatory authority inspectors, after appropriate notification. The verification of the CRF 
data must be made by direct inspection of source documents. The auditor may ask to visit the 
facilities where laboratory samples are collected, where the investigational product is stored 
and prepared and any other facility used during the study. These audits or inspections may 
take place at any time, during or after the study, and are based on the national regulations, as 
well as ICH guidelines.  
10.2 
STUDY MONITORING 
The Study Monitor will be responsible for ensuring adherence to FDA, ICH guidelines and 
the Sponsor’s or Sponsor’s designee Standard Operating Procedures. Study Monitors for this 
trial will be provided by the Sponsor. The monitors will follow the current “Guideline for the 
Monitoring of Clinical Investigators”, supplied by the FDA in compliance with ICH 
Guidelines. 
Experienced independent monitors or monitors from Clinical Research Organizations (CROs) 
will be trained by the Sponsor in order to standardize the monitoring procedure. These 
monitors will be trained on ICH GCP Guidelines, the Sponsor’s SOPs, study protocol and the 
study monitoring conventions. 
Regular monitoring of study data at each site will be performed in accordance with applicable 
regulations. Individual sites will be monitored to ensure that enrollment rate, data recording, 
and protocol adherence are satisfactory. The frequency of monitoring individual sites may 
fluctuate depending upon enrollment rate and the quantity of data collected and will be 
documented in the monitoring plan. 
These monitoring visits will be performed for the purposes of verifying adherence to the 
protocol and the completeness and exactness of data entered on the CRF. The study monitor 
will verify CRF entries by comparing them with the primary source documents 
(hospital/clinic/office records), which will be made available for this purpose. The monitor 
will review the maintenance of regulatory documentation and drug accountability. The 

 
 
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monitor will review the progress of the study with the Investigator and other site personnel on 
a regular basis. Case report form sections may be collected during these visits. At the end of 
the study, a close-out monitoring visit will be performed. Monitoring visits will be arranged 
in advance with site personnel at a mutually acceptable time. Sufficient time must be allowed 
by the site.  
Periodically, some or all of the facilities used in the study (e.g., local laboratory, pharmacy) 
may be reviewed. Monitoring visits will be arranged in advance with site personnel at a 
mutually acceptable time. Sufficient time must be allowed by the site personnel for the 
monitor to review CRFs and relevant source documents. The Investigator should be available 
to answer questions or resolve data clarifications. The Investigator or appointed delegate will 
receive the study monitor during these on-site visits, cooperate in providing the documents 
for inspection and respond to enquiries. 
The Investigator will ensure that the study participants are aware of and consent to their 
personal information being scrutinized during the data verification process, as part of study-
related monitoring, inspection and/or auditing, by properly authorized persons associated 
with Sponsor or by domestic and/or foreign regulatory authorities. However, the subject’s 
participation and personal information will be treated as strictly confidential to the extent that 
the applicable law permits and will not be made publicly available. 
Upon completion of the study, the study monitor will arrange for a final review of the study 
files after which the files should be secured for the appropriate time period. 
10.3 
QUALITY LABORATORY STANDARDS 
Laboratory tests or evaluations described in this protocol will be conducted in accordance 
with quality laboratory standards as described in the SOPs of the central and local institution 
laboratories. 
Before the study begins, the laboratories to be used in the study will provide a list of the 
reference ranges for all laboratory tests to be undertaken and details of the method used for 
quality control. These will be held in the Investigator Site File and the Trial Master File. The 
methods employed for each assay should be available on request. Any change in the 
laboratory, its procedures, references, values, etc. during the study must be notified promptly 
to the Sponsor. 
10.4 
STUDY DOCUMENTATION 
The Investigator must maintain primary source documents supporting CRF data entries. 
These documents, which are considered “source data”, should include documentation of: 
- 
Demographic information. 
- 
Evidence supporting the diagnosis/condition for which the subject is being studied 
- 
General information supporting the subject’s participation in the study. 
- 
Medical history and physical findings. 
- 
Hospitalization or Emergency Room records (if applicable). 
- 
Each study visit by date, including any relevant findings/notes by the 
investigator(s), occurrence (or lack) of adverse events, and changes in medication 
usage, including the date the study drug was commenced and completed. 
- 
Any additional visits during the study 

 
 
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- 
Any relevant telephone conversations with the subject regarding the study or 
possible adverse events. 
- 
Original, signed informed consent forms for study participation. 
The investigator must also retain all subject-specific printouts/reports of tests/procedures 
performed as a requirement of the study. During monitoring visits, the monitor will need to 
validate data in the CRFs against these source data. 
10.4.1 Source Document 
The Investigator will permit study-related monitoring, audits by or on behalf of the Sponsor, 
IRB/IEC review and regulatory inspections providing direct access to source data documents. 
Source documents are original records in which raw data are first recorded. These may be 
office/clinic/hospital records, charts, diaries, x-rays, laboratory results, printouts, pharmacy 
records, care records or completed scales for each study participant. Source documents 
should be kept in a secure and limited access area. All source documents must be accurate, 
clear, unambiguous, permanent and capable of being audited. They should be made using a 
permanent form of recording (ink, typing, printing, optical disc etc.). They should not be 
obscured by correcting fluid or have temporary attachments (such as removable self-stick 
notes). Source documents that are computer generated and stored electronically must be 
printed, signed and dated by the Investigator.  
Source data for subjects registered to the study should indicate the date the ICF was signed, 
participation in a clinical trial with the clinical protocol number and title, treatment number 
and evidence that inclusion/exclusion criteria have been met. 
10.4.2 Recording of Data on Case Report Form (CRF) 
The development of the CRF will be the responsibility of the Sponsor or its designee. 
All the pertinent data will be recorded on an electronic Case Report Form (eCRF). All eCRFs 
will be completed in English and will be reviewed by study monitors for accuracy and 
completeness. The eCRFs should be completed at the time of the subject's visit, with the 
exception of results of tests performed outside the Investigator’s office. The Investigator is 
responsible for verifying that all data entries in the eCRFs are accurate and correct. The 
Principal Investigator must sign the completed CRF prior to its submission to the Sponsor. 
A representative of the Sponsor or designee will instruct the Investigator and his/her staff 
prior to the enrollment of the first patient and will train them on recording the findings into 
the electronic data capture (EDC) system.  
(EDC) system on the electronic CRFs (eCRFs):   
After the enrollment of the first patient, a study monitor will periodically monitor the 
progress of the study by conducting onsite visits. This study monitor will also have the ability 
to review query statuses remotely, which may warrant more frequent contact with the 
Investigator and his/her staff. The Investigator will make available to the study monitor the 
computer that accesses the eCRFs, source documents, signed consent forms and all other 
study related documents. The Investigator will be responsible for reviewing eCRFs, 
providing resolution to data queries generated by the study monitor via the EDC system, 
providing missing or corrected data, and approving all changes performed on his/her data, 
and endorsing the patient data within the EDC system. This approval method will include 

 
 
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applying an electronic signature, a uniquely assigned username and a password, that together 
would represent a traditional handwritten signature. 
The Investigator will agree to the inspection of study-related records by the Sponsor, external 
auditor and/or health authority representatives. 
10.4.3 Investigator Site File 
All documents required for the conduct of the study as specified in the ICH-GCP guidelines 
and as defined by the sponsor will be maintained by the Investigator in an orderly manner and 
made available for monitoring and/or auditing by the Sponsor/or designee and regulatory 
agencies. 
10.5 
CLINICAL TRIAL SUPPLIES 
The Sponsor or designee will be responsible for supplying clinical trial supplies to the sites. 
Standard of care treatment, including G-CSF, will be provided by each site according to their 
standard of care. The Principal Investigator will be responsible for the administration, 
inventory and accountability of all clinical trial supplies provided to the site, exercising 
accepted medical and pharmaceutical practices. An accurate and timely record of the 
disposition of all clinical supplies must be maintained. The supplies and inventory record 
must be made available for inspection upon request. Upon completion or termination of the 
study, the Investigator will return the remaining clinical supplies along with a copy of the 
inventory record and a record of the clinical supplies returned. A copy of these records should 
be maintained in the site study files. Under no circumstances will the Investigator allow 
the study drugs to be used other than as directed by this protocol. 
Clinical trial supplies include, but are not limited to: CRFs, laboratory supplies, rescue 
medications and study drugs. 
10.6 
DATA MANAGEMENT 
Data Management services will be provided by the Sponsor or designee. The data 
management system will be specified in the Data Management Plan.   
After the data have been entered and verified, various edit checks will be performed for the 
purpose of ensuring the accuracy, integrity and validity of the database. These edit checks 
may include: 
- 
Missing value checks 
- 
Range checks 
- 
Consistency checks 
- 
Sequence checks 
- 
Protocol adherence checks 
Queries generated from these checks will be sent to the investigational site for resolution, and 
the database will be updated to reflect query resolutions as appropriate.  
Adverse events will be coded using the latest version of 
 
Prior and concomitant medications will be coded according to the World Health Organization 
Drug Dictionary.  

 
 
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11. 
STUDY ADMINISTRATION 
11.1 
REQUIRED DOCUMENTS PRIOR TO STUDY INITIATION 
Prior to the start of this study, all pre-investigational requirements must be met by the 
Investigator and study site. These may include: 
 Appropriate local health authority documentation properly signed and dated by the 
required Investigator (i.e., documents required for submission to the local IRB/IECs or 
applicable regulatory authorities).  
 Signed copy (original) of the approved protocol 
 Completed and signed statement of Investigator 
 A signed Clinical Trial Agreement 
 Curriculum vitae for the Investigator and sub-Investigator (can be collected at site 
initiation visit) 
 IRB/IEC name and address; and membership list (can be collected at site initiation 
visit) 
 Letter of approval from the IRB/IEC for both protocol (identified by protocol title and 
number) and ICF (identified by protocol title and number) 
 Copy of the IRB/IEC-approved written ICF to be used in the study (that has also been 
approved by the Sponsor) 
 Provisions for direct access to source/data documents, if necessary, for trial-related 
monitoring, audits, IRB/IEC review and regulatory inspection 
 Name and location of the laboratory utilized for laboratory assays and other facilities 
conducting tests, as well as a copy of the laboratory certificate and list of normal 
laboratory values (can be collected at site initiation visit) 
 In case a laboratory certification is not available, a written statement as to how the 
laboratory complies with quality assurance should be provided.   
 
Upon satisfactory receipt of all required regulatory documents, the Sponsor will arrange for 
study drugs to be delivered to the study site. Supply of all other study materials will be the 
responsibility of the Sponsor and/or designee. Subject entry should not begin until after the 
required regulatory documents are confirmed as received and the Investigator 
Meeting/Initiation Meeting has occurred. All personnel expected to be involved in the 
conduct of the study will undergo study initiation to include review of study protocol, 
instructions for CRF completion, AE reporting and overall responsibilities including those for 
drug accountability and study file maintenance. 
The Investigator and/or designee (study monitor) will be provided with an Investigator's File.  
This file should be used for all trial related documents. The Investigator will be responsible 
for keeping the Investigator's file updated and ensuring that all required documents are filed. 
The file will be inspected during monitoring visits. 
11.2 
STUDY COMPLETION 
The core study is expected to end when the last randomized subject has completed the 100 
days after transplantation and all query resolutions have been completed. Further the study 
will continue until the last randomized subjects complete 5 years. Data and materials that are 

 
 
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required before the study can be considered complete and/or terminated include, but are not 
limited to: 
 Laboratory findings, clinical data and all special test results from screening through the 
end of the follow-up period 
 CRF properly completed by appropriate study personnel and electronically signed by the 
Investigator 
 Completed Drug Accountability Records 
 Statement of outcome for each SAE reported 
 Copies of protocol amendments and IRB/IEC as well as relevant health authority 
approval/notification (if applicable) 
 Retention of Study Documents Statement 
11.3 
CLINICAL STUDY REPORT (CSR) 
Clinical Study Report (CSR) and supplements will be developed by the Sponsor according to 
sequence of the below-planned analyses. The CSR and supplements will be a clinical and 
statistical integrated report, according to the ICH E3 guideline. 
The sequence of planned statistical analyses for this study given in the planned chronological 
order is as follows:  
• 
The core set of the study accumulated data will be made available for statistical analyses 
of the primary study endpoint, engraftment-derived secondary endpoints and secondary 
short-term graft durability endpoint on the day the last randomized subject completes the 
Core Study Termination Visit (Visit 13), which will occur at his/her Day 100 following 
transplantation. The results and conclusions obtained from the integrative assessment of 
these efficacy endpoints, as well as accumulated safety data up to this cut-off date, will 
be summarized in a Clinical Study Report (CSR) in support of regulatory approval of 
BL-8040 + G-CSF for the treatment of Multiple Myeloma. 
• 
The second set of study accumulated data will be made available for statistical analyses 
of the long-term graft durability endpoints on the day the last randomized subject 
completes Visit 16, which will occur at 12 months following transplantation. The results 
and conclusions obtained from the integrative assessment of these secondary efficacy 
endpoints, as well as accumulated safety data up to this cut-off date, will be summarized 
in a supplement to the CSR in further support of regulatory approval of BL-8040 + 
G-CSF for the treatment of Multiple Myeloma. 
• 
The third and last set of study accumulated data will be made available for statistical 
analyses of the long-term exploratory endpoints at 5 years following the randomization 
of the last study subject. The results and conclusions obtained from the integrative 
assessment of these exploratory efficacy endpoints will be summarized in an additional 
supplement to the CSR in further support of the regulatory approval of BL-8040 + 
G-CSF for the mobilization for autologous stem cell transplantation in Multiple 
Myeloma. 
11.4 
RETENTION OF STUDY RECORDS 
The Investigator will retain copies of the approved protocol, completed CRF, signed ICFs, 
relevant source documents and all other supporting documentation related to the project as 
defined in ICH-E6 Section 8 related to the project per ICH-E6 record retention requirements. 
Records will be retained for at least 2 years after the last approval of a marketing application 

 
 
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in an ICH region and until there are no pending or contemplated marketing applications in an 
ICH region or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product, in a secure and safe facility with limited access. 
If the Investigator is unable to retain the study documents for the required amount of time, the 
Sponsor or designee must be informed of the individual who will be assuming this 
responsibility. 
The Sponsor will notify, in writing, the Investigator when the clinical study data may be 
discarded. The Investigator will take measures to prevent accidental or premature destruction 
of these documents.  
These files must be made available for inspection upon reasonable request by authorized 
representatives of the Sponsor and/or the relevant regulatory agencies. 
11.5 
CONFIDENTIALITY AND PUBLICATION OF STUDY RESULTS 
11.5.1 General 
All data and information supplied by or on behalf of the Sponsor or otherwise acquired or 
obtained by any Research Institution, the Principal Investigator and other Investigators 
("Recipients") in any manner, in connection with or in performance of this study, is 
considered "Confidential Information". This Confidential Information includes, but is not 
limited to, the Investigator’s brochure, this protocol and any information relating thereto, 
CRFs and other scientific data, information relating to Sponsor's Investigational Product and 
treatment methodology and information relating to Sponsor's (or its affiliates') commercial, 
technical and financial information, research technology, products, inventions, trade secrets 
and research and development. The results produced in performance of the study and any 
data, information or other material collected, developed, generated or prepared during and in 
the course of performing the study shall be promptly disclosed to Sponsor in full in writing, 
and are also considered Confidential Information. This Confidential Information shall be and 
remain the sole property of the Sponsor. Except for Publishable Results (defined below) to 
the extent it may be published under Section 11.6.2, throughout the duration of the study and 
after its completion, Recipients shall (i) not disclose Confidential Information to others 
without the written consent of the Sponsor, except to those of its employees who have a need 
to know the Confidential Information in order to Recipients' obligations hereunder, and 
where such employees are bound by written contractual obligations covering Confidential 
Information that are no less restrictive or protective than those contained herein, provided that 
Recipients shall remain liable for any disclosure or use of Confidential Information by such 
employees, (ii) use the same degree of care to preserve confidentiality of Confidential 
Information as they use for their own information of like nature, which shall not be less than 
reasonable degree of care, and (iii) not use Confidential Information for any purpose except 
in the performance of this study. Promptly at Sponsor's request, or upon completion of the 
study, Recipients will discontinue use and return to Sponsor or destroy, in accordance with 
Sponsor’s instructions, all copies or other manifestations of Confidential Information that 
may be in their possession or control, except to the extent expressly required hereunder and to 
comply with Applicable Laws (defined below). Should a Recipient be required to disclose 
Confidential Information pursuant to law, regulation, judicial or administrative order or 
request by a governmental or other entity authorized by law to make such request, Recipient 
shall (i) promptly notify Sponsor prior to such disclosure, (ii) cooperate with Sponsor and 
provide assistance in seeking a protective order or other suitable protection with respect to the 
Confidential Information, and (iii) only disclose such Confidential Information to the extent 

 
 
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pursuant to said law, regulation, judicial or administrative order, or request by a 
governmental or other authorized entity. 
At the subject's request, medical information may be given to his or her personal physician or 
other appropriate medical personnel responsible for his or her welfare. The personal 
physician will be notified by site personnel of subject participation in the study. 
11.5.2 Published Data 
The object of the study will be to publish the results of the complete study ("Publishable 
Results") in an appropriate peer-reviewed journal after the conclusion of the study 
("Publication").  A formal Publication of the Publishable Results is planned and will be 
considered a joint publication by the Principal Investigator, other Investigators, Sponsor and 
the appropriate Sponsor personnel (and Research Institutions) (Subject to internal review).  
Publication must be undertaken in a responsible and ethical manner, taking into account 
relevant external standards regarding the manner and content of scientific, technical and 
medical publications and in subject to applicable laws, rules, regulations, policies and 
guidelines ("Applicable Laws"). Authorship will be determined by mutual agreement 
between Sponsor and Principal Investigator.  Sponsor shall be mentioned in all Publications 
unless contrary instruction is given by Sponsor. Review and comment by Sponsor authorized 
personnel on draft abstracts and manuscripts for Publication or presentation is required prior 
to publication or presentation.  Authors shall submit a copy of any abstracts, manuscripts or 
other material proposed for publication or presentation ("Draft Publications") to the Sponsor 
for its approval no fewer than sixty (60) days prior to the intended date of submission of such 
Draft Publications to any journal, publisher, and/or third party. The Sponsor has the right, at 
its discretion (a) to evaluate Draft Publications for accuracy and concurrence regarding data, 
evaluations, and conclusions, (b) to provide an opportunity for Sponsor to share with the 
Investigator(s) any new or unpublished information of which he or she may be unaware, (c) 
to ensure that no Confidential Information or other Sponsor proprietary information is being 
utilized and has been included, and (d) evaluate Draft Publications to determine if patent 
applications need to be filed on any information disclosed therein.   
If the Sponsor determines that such Draft Publication contains Confidential Information or 
could otherwise be detrimental to Sponsor's intellectual property interest or have other 
adverse effects on its business, and notifies Principal Investigator of its determination, the 
Principal Investigator, Research Institutions and other Investigators/authors shall remove 
such Confidential Information from the Draft Publication or at Sponsor's election, modify it 
to remove language that is detrimental to Sponsor's intellectual property or other interests,  
and refrain from submitting such Draft Publication to a journal, publisher and/or other third 
party for additional ninety (90) days from Sponsor's notification to allow for filing of patent 
applications or the taking of such other measures as Sponsor deems appropriate to establish, 
preserve and protect its intellectual property or other interests. Principal Investigator, other 
Investigators and Research Institutions further agree to redact or modify those sections of the 
draft Publication which Sponsor in good faith determines falls within (a) to (d) above. 
 
 

 
 
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12. 
REFERENCES 
 
1.  Rajkumar SV. Multiple myeloma. Curr Probl Cancer. 2009;33(1):7-64. 
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2.  Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. 
Lancet Lond Engl. 2009;374(9686):324-339. doi:10.1016/S0140-6736(09)60221-X. 
3.  Ludwig H, Beksac M, Bladé J, et al. Current multiple myeloma treatment strategies with 
novel agents: a European perspective. The Oncologist. 2010;15(1):6-25. 
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4.  Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed 
multiple myeloma. Mayo Clin Proc. 2003;78(1):21-33. doi:10.4065/78.1.21. 
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doi:10.1016/j.hoc.2009.04.012. 
6.  Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of 
younger patients with multiple myeloma. Blood. 2008;111(5):2521-2526. 
doi:10.1182/blood-2007-08-104984. 
7.  Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma 
and the impact of novel therapies. Blood. 2008;111(5):2516-2520. doi:10.1182/blood-
2007-10-116129. 
8.  Ludwig H, Durie BGM, Bolejack V, et al. Myeloma in patients younger than age 50 years 
presents with more favorable features and shows better survival: an analysis of 10 549 
patients from the International Myeloma Working Group. Blood. 2008;111(8):4039-4047. 
doi:10.1182/blood-2007-03-081018. 
9.  Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046-1060. 
doi:10.1056/NEJMra1011442. 
10.  Attal M, Harousseau J-L, Stoppa A-M, et al. A prospective, randomized trial of autologous 
bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 
1996;335(2):91–97. 
11.  Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-
cell rescue for multiple myeloma. N Engl J Med. 2003;348(19):1875–1883. 
12.  Fermand J-P, Katsahian S, Divine M, et al. High-dose therapy and autologous blood stem-
cell transplantation compared with conventional treatment in myeloma patients aged 55 to 
65 years: long-term results of a randomized control trial from the Group Myelome-
Autogreffe. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23(36):9227-9233. 
doi:10.1200/JCO.2005.03.0551. 
13.  Blystad AK, Delabie J, Kvaløy S, et al. Infused CD34 cell dose, but not tumour cell 
content of peripheral blood progenitor cell grafts, predicts clinical outcome in patients with 
diffuse large B-cell lymphoma and follicular lymphoma grade 3 treated with high-dose 
therapy. Br J Haematol. 2004;125(5):605-612. doi:10.1111/j.1365-2141.2004.04951.x. 
14.  Toor AA, Ayers J, Strupeck J, et al. Favourable results with a single autologous stem cell 
transplant following conditioning with busulphan and cyclophosphamide in patients with 
multiple myeloma. Br J Haematol. 2004;124(6):769-776. 

 
 
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15.  Stiff P, Gingrich R, Luger S, et al. A randomized phase 2 study of PBPC mobilization by 
stem cell factor and filgrastim in heavily pretreated patients with Hodgkin’s disease or 
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16.  Tricot G, Jagannath S, Vesole D, et al. Peripheral blood stem cell transplants for multiple 
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Blood. 1995;85(2):588-596. 
17.  Demirer T, Buckner CD, Gooley T, et al. Factors influencing collection of peripheral blood 
stem cells in patients with multiple myeloma. Bone Marrow Transplant. 1996;17(6):937-
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18.  Desikan KR, Barlogie B, Jagannath S, et al. Comparable engraftment kinetics following 
peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor 
with or without cyclophosphamide in multiple myeloma. J Clin Oncol Off J Am Soc Clin 
Oncol. 1998;16(4):1547-1553. doi:10.1200/JCO.1998.16.4.1547. 
19.  Perea G, Sureda A, Martino R, et al. Predictive factors for a successful mobilization of 
peripheral blood CD34+ cells in multiple myeloma. Ann Hematol. 2001;80(10):592-597. 
20.  DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo 
and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in 
patients with multiple myeloma. Blood. 2009;113(23):5720-5726. doi:10.1182/blood-
2008-08-174946. 
21.  Abraham M, Beider K, Wald H, et al. The CXCR4 antagonist 4F-benzoyl-TN14003 
stimulates the recovery of the bone marrow after transplantation. Leukemia. 
2009;23(8):1378-1388. 
22.  Abraham M, Biyder K, Begin M, et al. Enhanced unique pattern of hematopoietic cell 
mobilization induced by the CXCR4 antagonist 4F-benzoyl-TN14003. Stem Cells Dayt 
Ohio. 2007;25(9):2158-2166. 
23.  Abraham M, Weiss ID, Wald H, et al. Sequential administration of the high affinity 
CXCR4 antagonist BKT140 promotes megakaryopoiesis and platelet production. Br J 
Haematol. 2013;163(2):248-259. doi:10.1111/bjh.12501. 
 

 
PRIVILEGED & CONFIDENTIAL 
 
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1 Dosing during Day 6, 7 and 8 will be conducted upon failure to collect ≥ 6x106 CD34+ cells in the apheresis content.  
2 To be performed pre-dose 
3 Includes race, gender, etc.  
4 For patients who need 2nd BL-8040 dose administration 
5 Within one hour prior to BL-8040/Placebo administration if premedication is given orally, or ~15 minutes prior to study drug administration if premedication is given IV 
6 In Part 1, BL-8040 administration only 
7 Following G-CSF administration 
8 Screening biopsy will be required only for CR/sCR patients. A bone marrow biopsy sample taken up to 30 days before signing the ICF may be used for screening. 
9 All AEs will be collected starting from ICF signature and up to 30 days from the last dose of study drug 
10 For subjects with moderate or severe renal impairment with abnormal clinically significant changes after the first BL-8040/Placebo dose, this procedure will be performed weekly until recovery or 
stabilization. Biochemistry should be performed with GFR assessment. 
11 From Visit 11 and on only disease related medications will be recorded   
12 Triplicate ECGs Pre-dose (up to 1 hour before BL-8040 administration) and 30-45 minutes post-dose 
13 Triplicate ECGs prior to apheresis and G-CSF administration 
14 ECG for local assessment will be done ONLY for moderate/severe renal impairment subjects. 
15 Will be done ONLY for moderate/severe renal impairment subjects. 
16 Will be done for all moderate/severe renal impairment subjects or for subjects who did not achieve collection goal at Day 7.  
17 At Day 5, only weight will be recorded and will be measured prior to apheresis  
18 Only if G-CSF was administered at the site. 
19 Will be done for all moderate/severe renal impairment subjects regardless of the amount of cells collected in the apheresis and for subjects who did not achieve collection goal at Day 5. 
20 Will be done for all moderate/severe renal impairment subjects who received second dose of BL-8040/Placebo regardless of the amount of cells collected in the apheresis and for subjects who did 
not achieve collection goal at Day 7. 
21 Blood biochemistry includes Na+, K+, calcium, uric acid, phosphorus, glucose, total bilirubin, AST, ALT, LDH, ALP, BUN and creatinine.   
22 Will be done for all moderate/severe renal impairment subjects or for subjects who did not achieve collection goal at day 7.  
23 Serology assessment includes HIV antibodies (HIV1 and HIV2), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (Hep C Ab). 
24 CD34+ Enumeration in PB should be collected before G-CSF administration. This assessment will be done locally in Part 1 and locally and at the central laboratory in Part 2 
25 CD34+ Enumeration in Apheresis Product will be done by locally in Part 1 and locally and at the central laboratory in Part 2 
26 Female subjects must be of non-childbearing potential or, if of childbearing potential, must have a negative serum pregnancy test at screening and negative urine/serum pregnancy test within 72 
hours prior to G-CSF first administration. 
27 Blood samples for BL-8040 or its metabolites PK analysis will be collected during Part 1 on Day 4 and Day 6 at pre-dose of BL-8040 and 0.25, 0.5, 1, 2, 4 and 8 hrs post BL-8040 administration. 
Additional PK sample will be collected 12 hrs (+/-2hrs) post BL-8040 administration, before the apheresis on Days 5 and 7. Please refer to the laboratory manual for additional information. 
 
 

 
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Protocol: BL-8040.SCM.301 
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28 Blood samples for BL-8040 or its metabolites PK analysis will be collected during Part 2 on Days 4 and 6 at pre-dose of BL-8040 and 40-60 minutes and 2-6 hours post BL-8040 administration. 
Additional PK sample will be collected 10-14 hours post BL-8040 administration, before the apheresis on Days 5 and 7. Please refer to the laboratory manual for additional information. 
29 Blood samples for ADA for both parts will be collected on Day 4  up to 1 hour pre-dose of BL-8040 and on Visits 9 (pre chemotherapy) and 11 Please refer to the laboratory manual for additional 
information. 
30 Blood samples for Mast Cell Activation and Complement Activation in both parts of the study will be collected on Day 4 up to 1 hour pre-dose of BL-8040 and 2 hours post BL-8040 
administration (Post dose defined as end time of administration) (±15 minutes). Please refer to the laboratory manual for additional information.