A Phase III, Safety, Tolerability and Efficacy of Combination Treatment of BL-8040 and Granulocyte Colony Stimulating Factor (G-CSF) as Compared to Placebo and G-CSF for the Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Subjects With Multiple Myeloma (MM)

NCT ID: NCT03246529

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-23
• Study Completion Date: 2029-09-30

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

BL-8040 1.25 mg/kg + G-CSF

Double-blind placebo-controlled setting designed to assess the safety, tolerability and efficacy of G-CSF + BL-8040 as compared to G-CSF + Placebo, for stem cell mobilization in MM.

Group Type: EXPERIMENTAL

BL-8040 1.25 mg/kg + G-CSF

Intervention Type: DRUG

Up to 2 subcutaneous (SC) injections of BL-8040 are anticipated during the study. Injections of G-CSF per standard of care

Placebo + G-CSF

Double-blind placebo-controlled setting designed to assess the safety, tolerability and efficacy of G-CSF + BL-8040 as compared to G-CSF + Placebo, for stem cell mobilization in MM.

Group Type: ACTIVE_COMPARATOR

Placebo +G-CSF

Intervention Type: DRUG

Up to 2 SC injections of Placebo are anticipated during the study. Injections of G-CSF per standard of care

Interventions

BL-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

Intervention Type: DRUG

Placebo +G-CSF

Up to 2 SC injections of Placebo are anticipated during the study. Injections of G-CSF per standard of care

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 78 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioLineRx, Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John DiPersio, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Crees Zachary, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

UCLA Medical Center

Los Angeles, California, United States

University of Florida

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

Loyola University Medical Center

Chicago, Illinois, United States

University of Maryland

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

The Washington University School of Medicine

St Louis, Missouri, United States

University of Cincinnati

Cincinnati, Ohio, United States

MD Anderson Cancer Center

Houston Texas, Texas, United States

Huntsman Cancer Institute in University of Utah

Salt Lake City, Utah, United States

University of Koln

Cologne, Koln, Germany

Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases

Budapest, , Hungary

University of Debrecen

Debrecen, , Hungary

Div. Clinicizzata di Ematologia - Policlinico Vittorio Emanuele

Catania, , Italy

Presidio Ospedaliero Morelli Viale Europa

Reggio Calabria, , Italy

Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

Hospital University Ramon y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Countries

United States; Germany; Hungary; Italy; Spain

References

Crees ZD, Rettig MP, Jayasinghe RG, Stockerl-Goldstein K, Larson SM, Arpad I, Milone GA, Martino M, Stiff P, Sborov D, Pereira D, Micallef I, Moreno-Jimenez G, Mikala G, Coronel MLP, Holtick U, Hiemenz J, Qazilbash MH, Hardy N, Latif T, Garcia-Cadenas I, Vainstein-Haras A, Sorani E, Gliko-Kabir I, Goldstein I, Ickowicz D, Shemesh-Darvish L, Kadosh S, Gao F, Schroeder MA, Vij R, DiPersio JF. Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. Nat Med. 2023 Apr;29(4):869-879. doi: 10.1038/s41591-023-02273-z. Epub 2023 Apr 17.

Reference Type: DERIVED

PMID: 37069359 (View on PubMed)

Crees ZD, Stockerl-Goldstein K, Vainstein A, Chen H, DiPersio JF. GENESIS: Phase III trial evaluating BL-8040 + G-CSF to mobilize hematopoietic cells for autologous transplant in myeloma. Future Oncol. 2019 Nov;15(31):3555-3563. doi: 10.2217/fon-2019-0380. Epub 2019 Sep 9.

Reference Type: DERIVED

PMID: 31495201 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

BL-8040.SCM.301

Identifier Type: -

Identifier Source: org_study_id