Multiple Myeloma
Conditions
Brief summary
A total of 122 subjects were randomized into the study and investigated in the double-blind placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared to G-CSF + placebo.
Detailed description
* Part 1: This lead-in period, designed to ascertain the dose of BL-8040, enrolled a total of 12 subjects to an open labeled treatment to assess the efficacy, safety, pharmacokinetic (PK) and pharmacodynamic (PD) parameters of treatment with G-CSF 10 µg/kg/day and BL-8040 1.25 mg/kg, per study protocol to goal collection of ≥ 6 × 10\^6 CD34+ cells/kg. * Part 2: Following the successful completion of Part 1, a total of 122 subjects were randomized into Part 2 of the study which employed a double-blind placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared to G-CSF + placebo.
Interventions
DRUGBL-8040 1.25 mg/kg + G-CSF
Up to 2 subcutaneous (SC) injections of BL-8040 are anticipated during the study. Injections of G-CSF per standard of care
DRUGPlacebo +G-CSF
Up to 2 SC injections of Placebo are anticipated during the study. Injections of G-CSF per standard of care
Sponsors
BioLineRx, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Subjects were randomized using a 2:1 ratio to receive G-CSF + BL-8040 or G-CSF + Placebo, respectively. Randomization will use permuted blocks stratifying subjects by US geographical region (NorthEast, SouthEast, MidWest, SouthWest and NorthWest), remission status (CR vs. PR), and baseline platelet count (\< 200 × 10\^9/L or ≥ 200 × 10\^9/L).
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed Multiple Myeloma prior to enrolment and randomization. 2. At least 1 week (7 days) from last induction cycle of combination/multi-agent cyto-reductive chemotherapy (e.g., KRD \[carfilzomib, lenalidomide, dexamethasone\] or VRD (e.g., 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. 3. Eligible for autologous hematopoietic stem cell transplantation according to the Investigator's discretion. 4. The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 6. Adequate organ function at screening as defined as below: 1. Hematology: * White blood cell counts more than 2.5 x 10\^9/L * Absolute neutrophil count more than 1.5 x 10\^9/L 2. Platelet count more than 100 x10\^9/L Renal Function: • Glomerular Filtration Rate (GFR) value of ≥15 mL/min/1.732 calculated by Modification of Diet in Renal Disease (MDRD) equation 3. Hepatic function: * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x ULN * Total Bilirubin ≤ 2.0 x Upper Limit Normal (ULN) unless the subject has Gilbert disease 4. Coagulation test: * International Normalized Ratio (INR) or Prothrombin Time (PT): ≤1.5 x ULN unless subject is receiving anticoagulant therapy, as long as PT or Partial Thromboplastin Time (PTT) is within therapeutic range of intended use of anticoagulants * Activated Partial Thromboplastin Time (aPTT): ≤1.5 x ULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants 7. 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. 8. Patients must have a signed study informed consent prior to entering the study.
Exclusion criteria
1. Previous history of autologous or allogeneic-Hematopoietic Cell Transplantation (HCT). 2. Failed previous Hematopoietic Stem Cell (HSC) collections or collection attempts. 3. Taken any of the listed below concomitant medications, growth factors or stimulating agents within the designated washout period: 1. Dexamethasone: 7 days; 2. Thalidomide: 7 days; 3. Lenalidomide: 7 days; 4. Pomalidomide: 7 days; 5. Bortezomib: 7 days; 6. Carfilzomib: 7 days; 7. G-CSF: 14 days; 8. Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) or Neulasta®: 21 days; 9. Erythropoietin or erythrocyte stimulating agents: 30 days; 10. Eltrombopag, romiplostim or platelet stimulating agents: 30 days; 11. Carmustine (BCNU): 42 days/6 weeks; 12. Daratumumab: 28 days; 13. 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. 9. Plans to receive maintenance treatment within 60 days post-engraftment (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 central nervous system (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, coronary artery bypass grafting (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 New York Heart Association (NYHA) Heart Failure \>2. 21. ECG in screening showing QTcF \> 470 msec, and/or PR \> 280 msec,. 22. Mobitz II 2nd degree Atrioventricular (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 breastfeeding, or expecting to conceive 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg With up to 2 Apheresis Sessions | From first day of study treatment (G-CSF) until day of second apheresis which was planned to occur on Day 6 | Percentage of subjects mobilizing ≥6 × 10\^6 CD34+ cells/kg with up to 2 apheresis sessions in preparation for autologous hematopoetic cell transplantation (auto-HCT) after treatment with G-CSF + single administration of BL-8040/placebo. Based on central laboratory data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Platelet Engraftment, After Auto-HCT | End of engraftment period, which was defined as 29 days post transplantation | Time to platelet engraftment, after auto-HCT, where engraftment was defined as the first of 3 consecutive measurements of platelet count ≥20 × 10\^9/L without platelet transfusion support for 7 days following the conditioning regimen associated nadir. |
| Graft Durability at 6 Months Post Transplantation | 6 Months Post Transplantation | Comparability of the graft durability between the BL-8040 + G-CSF arm and the placebo + G-CSF arm at 6 months post transplantation |
| Graft Durability at 9 Months Post Transplantation | 9 Months Post Transplantation | Comparability of the graft durability between the BL-8040 + G-CSF arm and the placebo + G-CSF arm at 9 months post transplantation |
| Graft Durability at 12 Months Post Transplantation | 12 Month Post Transplantation | Comparability of the graft durability between the BL-8040 + G-CSF arm and the placebo + G-CSF arm at 12 months post transplantation |
| Percentage of Subjects Mobilizing ≥2 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | From first day of study treatment (G-CSF) until day of first apheresis which was planned to occur on Day 5 | Percentage of subjects mobilizing ≥2 × 10\^6 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040/ placebo. |
| Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | From first day of study treatment (G-CSF) until day of first apheresis which was planned to occur on Day 5 | Percentage of subjects mobilizing ≥6 × 10\^6 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040/ placebo. |
| Time to Neutrophil Engraftment, After Auto-HCT | End of engraftment period, which was defined as 29 days post transplantation | Time to neutrophil engraftment after auto-HCT, where engraftment was defined as absolute neutrophil count (ANC) ≥0.5 × 10\^9/L for 3 days or ≥1.0 × 10\^9/L for 1 day following the conditioning regimen associated nadir. |
| Subjects With Graft Durability at 100 Days Post Transplant/ Early Termination | Day 100 Post-Transplantation (± 7 days) | Subjects achieving graft durability were defined as meeting the following 2 criteria: * Platelet count ≥50 × 10\^9/L without transfusion for at least 2 weeks. * Hemoglobin level ≥10 g/dL with no erythropoietin support or transfusions for at least 1 month. This analysis was performed in part 2 of the study only. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Annualized Relapse Rate Until September 2028 | End of Study | Comparability between the effect of BL-8040 + G-CSF and placebo + G-CSF on Annualized Relapse Rate until September 2028 |
| Relapse Free Survival Until September 2028 | End Of Study | Comparability between the effect of BL-8040 + G-CSF and placebo + G-CSF on Relapse Free Survival until September 2028 |
| Overall Survival Until September 2028 | End of Study | Comparability between the effect of BL-8040 + G-CSF and placebo + G-CSF on Overall Survival until September 2028 |
Countries
Germany, Hungary, Italy, Spain, United States
Participant flow
Recruitment details
A total of 180 subjects signed the Informed Consent Form (ICF) and screened to the study. A total of 136 subjects received at least one dose of G-CSF. A total of 134 subjects were treated with G-CSF and with BL-8040 or Placebo.
Participants by arm
| Arm | Count |
|---|---|
| BL-8040 + G-CSF Part 1 Part 1 (lead-in) period. G-CSF given one time daily s.c. for 5-8 days (Day 1 up to 8) at doses of approximately 10 µg/kg/day but not more than 15 µg/kg/day. BL-8040 1.25 mg/kg s.c. on Day 4 (and Day 6, if needed).
First apheresis on Day 5 with up to 3 additional procedures possible until Day 8, as needed. | 12 |
| BL-8040 + G-CSF Part 2 Part 2: randomized, double-blinded, placebo controlled period. G-CSF given one time daily s.c. for 5-8 days (Day 1 up to 8) at doses of approximately 10 µg/kg/day but not more than 15 µg/kg/day. BL-8040 1.25 mg/kg s.c. on Day 4 (and Day 6, if needed).
First apheresis on Day 5 with up to 3 additional procedures possible until Day 8, as needed. | 80 |
| Placebo + G-CSF Part 2 Part 2: randomized, double-blinded, placebo controlled period. G-CSF given one time daily s.c. for 5-8 days (Day 1 up to 8) at doses of approximately 10 µg/kg/day but not more than 15 µg/kg/day. Placebo s.c. on Day 4 (and Day 6, if needed).
First apheresis on Day 5 with up to 3 additional procedures possible until Day 8, as needed. | 42 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Core Study (until 100 d post-transplant) | Adverse Event | 0 | 2 | 0 |
| Core Study (until 100 d post-transplant) | Lost to Follow-up | 0 | 1 | 1 |
| Core Study (until 100 d post-transplant) | Other Reasons | 0 | 2 | 2 |
| Core Study (until 100 d post-transplant) | Physician Decision | 0 | 0 | 1 |
| Core Study (until 100 d post-transplant) | Withdrawal by Subject | 0 | 1 | 4 |
| Follow-up period at 1 year FU Completion | Death | 0 | 0 | 1 |
| Follow-up period at 1 year FU Completion | Disease progression | 2 | 1 | 1 |
| Follow-up period at 1 year FU Completion | Lost to Follow-up | 1 | 3 | 0 |
| Follow-up period at 1 year FU Completion | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | BL-8040 + G-CSF Part 1 | Total | Placebo + G-CSF Part 2 | BL-8040 + G-CSF Part 2 |
|---|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 4.8 | 60.5 years STANDARD_DEVIATION 9.1 | 59.2 years STANDARD_DEVIATION 9.6 | 60.4 years STANDARD_DEVIATION 9.4 |
| IMWG Classification at Screening CR (Complete Response) | 2 Participants | 21 Participants | 7 Participants | 12 Participants |
| IMWG Classification at Screening PR (Partial Response) | 0 Participants | 41 Participants | 10 Participants | 31 Participants |
| IMWG Classification at Screening sCR (Stringent Complete Response) | 1 Participants | 7 Participants | 2 Participants | 4 Participants |
| IMWG Classification at Screening VGPR (Very Good Partial Response) | 9 Participants | 65 Participants | 23 Participants | 33 Participants |
| Months from MM Diagnosis to Study Consent | 4.6 months STANDARD_DEVIATION 0.9 | 6.3 months STANDARD_DEVIATION 9.4 | 6.4 months STANDARD_DEVIATION 6.9 | 6.5 months STANDARD_DEVIATION 11.1 |
| Race/Ethnicity, Customized African | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized African American | 2 Participants | 12 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 9 Participants | 114 Participants | 40 Participants | 65 Participants |
| Race/Ethnicity, Customized Hispanic origin | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Specified | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Germany | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Hungary | 0 Participants | 16 Participants | 6 Participants | 10 Participants |
| Region of Enrollment Italy | 0 Participants | 17 Participants | 8 Participants | 9 Participants |
| Region of Enrollment Spain | 0 Participants | 8 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 12 Participants | 90 Participants | 26 Participants | 52 Participants |
| Sex: Female, Male Female | 5 Participants | 48 Participants | 18 Participants | 25 Participants |
| Sex: Female, Male Male | 7 Participants | 86 Participants | 24 Participants | 55 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Bortezomib | 7 Participants | 89 Participants | 28 Participants | 54 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Cisplatin | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Cyclophosphamide | 0 Participants | 9 Participants | 4 Participants | 5 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Daratumumab 0 - 1 2.4% | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Doxorubicin | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Etoposide | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Ixazomib | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Kyprolis | 6 Participants | 9 Participants | 1 Participants | 2 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Lenalidomide | 12 Participants | 97 Participants | 28 Participants | 57 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Melphalan | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Pomalidomide | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Treatment Indicated for Multiple Myeloma Before Study Initiation Thalidomide | 0 Participants | 30 Participants | 12 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 2 / 80 | 1 / 42 |
| other Total, other adverse events | 12 / 12 | 77 / 80 | 35 / 42 |
| serious Total, serious adverse events | 1 / 12 | 7 / 80 | 0 / 42 |
Outcome results
Primary
Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg With up to 2 Apheresis Sessions
Percentage of subjects mobilizing ≥6 × 10\^6 CD34+ cells/kg with up to 2 apheresis sessions in preparation for autologous hematopoetic cell transplantation (auto-HCT) after treatment with G-CSF + single administration of BL-8040/placebo. Based on central laboratory data.
Time frame: From first day of study treatment (G-CSF) until day of second apheresis which was planned to occur on Day 6
Population: Full Analysis Set (FAS) for Part 1 (Part 1 of the study assessed the mobilization using local lab only), Intention-to-Treat (ITT) for Part 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BL-8040 + G-CSF Part 1 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg With up to 2 Apheresis Sessions | Local Lab | 91.7 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg With up to 2 Apheresis Sessions | Central Lab | 70.0 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg With up to 2 Apheresis Sessions | Local Lab | 92.5 Percentage of responders |
| Placebo + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg With up to 2 Apheresis Sessions | Central Lab | 14.3 Percentage of responders |
| Placebo + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg With up to 2 Apheresis Sessions | Local Lab | 26.2 Percentage of responders |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Graft Durability at 12 Months Post Transplantation
Comparability of the graft durability between the BL-8040 + G-CSF arm and the placebo + G-CSF arm at 12 months post transplantation
Time frame: 12 Month Post Transplantation
Population: Post Transplantation Analysis Set (all randomized subjects treated, with at least 1 apheresis session, and who underwent transplantation).~Graft durability was not assessed during Part 1 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BL-8040 + G-CSF Part 1 | Graft Durability at 12 Months Post Transplantation | 81.8 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Graft Durability at 12 Months Post Transplantation | 81.1 Percentage of responders |
Secondary
Graft Durability at 6 Months Post Transplantation
Comparability of the graft durability between the BL-8040 + G-CSF arm and the placebo + G-CSF arm at 6 months post transplantation
Time frame: 6 Months Post Transplantation
Population: Post Transplantation Analysis Set (all randomized subjects treated, with at least 1 apheresis session, and who underwent transplantation).~Graft durability was not assessed during Part 1 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BL-8040 + G-CSF Part 1 | Graft Durability at 6 Months Post Transplantation | 80.5 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Graft Durability at 6 Months Post Transplantation | 83.8 Percentage of responders |
Secondary
Graft Durability at 9 Months Post Transplantation
Comparability of the graft durability between the BL-8040 + G-CSF arm and the placebo + G-CSF arm at 9 months post transplantation
Time frame: 9 Months Post Transplantation
Population: Post Transplantation Analysis Set (all randomized subjects treated, with at least 1 apheresis session, and who underwent transplantation).~Graft durability was not assessed during Part 1 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BL-8040 + G-CSF Part 1 | Graft Durability at 9 Months Post Transplantation | 83.1 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Graft Durability at 9 Months Post Transplantation | 81.1 Percentage of responders |
Secondary
Percentage of Subjects Mobilizing ≥2 × 10^6 CD34+ Cells/kg in 1 Apheresis Session
Percentage of subjects mobilizing ≥2 × 10\^6 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040/ placebo.
Time frame: From first day of study treatment (G-CSF) until day of first apheresis which was planned to occur on Day 5
Population: FAS for Part 1 (Part 1 of the study assessed the mobilization using local lab only), ITT for Part 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BL-8040 + G-CSF Part 1 | Percentage of Subjects Mobilizing ≥2 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Local Lab | 100 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥2 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Central Lab | 87.5 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥2 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Local Lab | 96.3 Percentage of responders |
| Placebo + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥2 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Central Lab | 47.6 Percentage of responders |
| Placebo + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥2 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Local Lab | 64.3 Percentage of responders |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg in 1 Apheresis Session
Percentage of subjects mobilizing ≥6 × 10\^6 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040/ placebo.
Time frame: From first day of study treatment (G-CSF) until day of first apheresis which was planned to occur on Day 5
Population: FAS for Part 1 (Part 1 of the study assessed the mobilization using local lab only), ITT for Part 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BL-8040 + G-CSF Part 1 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Local Lab | 75 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Central Lab | 67.5 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Local Lab | 88.8 Percentage of responders |
| Placebo + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Central Lab | 4.8 Percentage of responders |
| Placebo + G-CSF Part 2 | Percentage of Subjects Mobilizing ≥6 × 10^6 CD34+ Cells/kg in 1 Apheresis Session | Local Lab | 9.5 Percentage of responders |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Subjects With Graft Durability at 100 Days Post Transplant/ Early Termination
Subjects achieving graft durability were defined as meeting the following 2 criteria: * Platelet count ≥50 × 10\^9/L without transfusion for at least 2 weeks. * Hemoglobin level ≥10 g/dL with no erythropoietin support or transfusions for at least 1 month. This analysis was performed in part 2 of the study only.
Time frame: Day 100 Post-Transplantation (± 7 days)
Population: Post Transplantation analysis set (all randomized subjects treated, with at least 1 apheresis session, and who underwent transplantation).~Graft durability was not assessed during Part 1 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BL-8040 + G-CSF Part 1 | Subjects With Graft Durability at 100 Days Post Transplant/ Early Termination | 92.2 Percentage of responders |
| BL-8040 + G-CSF Part 2 | Subjects With Graft Durability at 100 Days Post Transplant/ Early Termination | 91.9 Percentage of responders |
Secondary
Time to Neutrophil Engraftment, After Auto-HCT
Time to neutrophil engraftment after auto-HCT, where engraftment was defined as absolute neutrophil count (ANC) ≥0.5 × 10\^9/L for 3 days or ≥1.0 × 10\^9/L for 1 day following the conditioning regimen associated nadir.
Time frame: End of engraftment period, which was defined as 29 days post transplantation
Population: Post Transplantation analysis set (all subjects treated, with at least 1 apheresis session, and who underwent transplantation)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BL-8040 + G-CSF Part 1 | Time to Neutrophil Engraftment, After Auto-HCT | 12 Days |
| BL-8040 + G-CSF Part 2 | Time to Neutrophil Engraftment, After Auto-HCT | 12 Days |
| Placebo + G-CSF Part 2 | Time to Neutrophil Engraftment, After Auto-HCT | 12 Days |
Secondary
Time to Platelet Engraftment, After Auto-HCT
Time to platelet engraftment, after auto-HCT, where engraftment was defined as the first of 3 consecutive measurements of platelet count ≥20 × 10\^9/L without platelet transfusion support for 7 days following the conditioning regimen associated nadir.
Time frame: End of engraftment period, which was defined as 29 days post transplantation
Population: Post Transplantation analysis set (all subjects treated, with at least 1 apheresis session, and who underwent transplantation)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BL-8040 + G-CSF Part 1 | Time to Platelet Engraftment, After Auto-HCT | 17 Point estimate (days) |
| BL-8040 + G-CSF Part 2 | Time to Platelet Engraftment, After Auto-HCT | 18 Point estimate (days) |
| Placebo + G-CSF Part 2 | Time to Platelet Engraftment, After Auto-HCT | 17 Point estimate (days) |
Other Pre-specified
Annualized Relapse Rate Until September 2028
Comparability between the effect of BL-8040 + G-CSF and placebo + G-CSF on Annualized Relapse Rate until September 2028
Time frame: End of Study
Other Pre-specified
Overall Survival Until September 2028
Comparability between the effect of BL-8040 + G-CSF and placebo + G-CSF on Overall Survival until September 2028
Time frame: End of Study
Other Pre-specified
Relapse Free Survival Until September 2028
Comparability between the effect of BL-8040 + G-CSF and placebo + G-CSF on Relapse Free Survival until September 2028
Time frame: End Of Study