BL-8040 + G-CSF for Multiple Myeloma

(GENESIS Trial)

Recruiting at 23 trial locations

Overseen By Inbal Goldstein, Ph.D

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BioLineRx, Ltd.

Must not be taking: Thalidomide, Lenalidomide, Bortezomib, others

Disqualifiers: Previous HCT, Active infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6 days

180 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications before joining the trial. There is a required period without taking specific drugs like dexamethasone, lenalidomide, and others, ranging from 7 to 42 days, depending on the medication.

What data supports the effectiveness of the drug BL-8040 + G-CSF for Multiple Myeloma?

Research shows that G-CSFs like Filgrastim (Neupogen) are effective in reducing chemotherapy-induced neutropenia (low white blood cell count) in cancer patients, which suggests they may help support the immune system during treatment for conditions like Multiple Myeloma. ^{1 2 3 4 5}

Is the combination of BL-8040 and G-CSF safe for humans?

Filgrastim (also known as Neupogen and its biosimilars like Zarxio and Nivestym) is generally considered safe for use in humans, as it has been widely used to treat neutropenia (a low level of white blood cells) in cancer patients receiving chemotherapy. Studies have shown that these drugs are safe when used as intended, with no major safety concerns reported in healthy volunteers. ^{1 3 5 6 7}

What makes the drug BL-8040 + G-CSF unique for treating multiple myeloma?

BL-8040 + G-CSF is unique because it combines a novel drug, BL-8040, with G-CSF (a growth factor that stimulates the production of white blood cells) to potentially enhance the immune response against multiple myeloma, which is different from other treatments that primarily focus on targeting cancer cells directly. ^{8 9 10 11 12}

Research Team

John F Dipersio, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Crees Zachary, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with Multiple Myeloma in first or second complete or partial remission, good performance status, and proper organ function. They must be eligible for stem cell transplant and not have had previous transplants, failed collections, certain medications recently, live vaccines within 30 days, active CNS metastases, other trials participation, serious health issues that could affect the trial's outcome or are pregnant/breastfeeding.

Inclusion Criteria

My cancer is responding to treatment and is in the first or second stage of partial or complete response.

I am fully active or restricted in physically strenuous activity but can do light work.

My blood, kidney, liver, and clotting tests are within normal ranges.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

Underlying medical condition that would preclude study participation

Your blood oxygen level is less than 92% when breathing normally.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in

Open-label treatment to assess the efficacy, safety, pharmacokinetic (PK) and pharmacodynamic (PD) parameters of treatment with G-CSF and BL-8040

Not specified

Treatment

Double-blind placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared to G-CSF + placebo

6 days

Up to 2 apheresis sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including engraftment and graft durability

12 months

Long-term Follow-up

Comparability between the effect of BL-8040 + G-CSF and placebo + G-CSF on overall survival and relapse-free survival

Until September 2028

Treatment Details

Interventions

• BL-8040
• G-CSF
• Placebo

Trial Overview The study compares the safety and effectiveness of a combination treatment using BL-8040 with G-CSF versus a placebo with G-CSF to mobilize hematopoietic stem cells for autologous transplantation in Multiple Myeloma patients. It's a double-blind study where neither participants nor researchers know who gets the real treatment until after results are collected.

Participant Groups

Group I: BL-8040 1.25 mg/kg + G-CSF Experimental Treatment 1 Intervention

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 II: Placebo + G-CSF Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

BioLineRx, Ltd.

Lead Sponsor

Trials

24

Recruited

2,200+

Findings from Research

Pegfilgrastim is as effective or even more effective than filgrastim in reducing chemotherapy-induced neutropenia, making it a strong option for patients undergoing cancer treatment.

One of the key benefits of pegfilgrastim is that it can be administered just once per chemotherapy cycle, which may improve patient compliance and enhance their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim; a neutrophil mediated granulocyte colony stimulating factor-expanding uses in cancer chemotherapy. Morishita, M., Leonard, RC.[2022]

In a study involving 348 breast cancer patients undergoing chemotherapy, the new G-CSF XM02 was found to significantly reduce the duration of severe neutropenia compared to a placebo, with a mean duration of 1.1 days for both XM02 and Neupogen, versus 3.9 days for placebo.

XM02 demonstrated similar safety profiles to Neupogen, indicating that it is an effective alternative for managing chemotherapy-induced neutropenia without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. del Giglio, A., Eniu, A., Ganea-Motan, D., et al.[2022]

Filgrastim-sndz (Zarxio) became the first biosimilar approved by the FDA in the US on March 6, 2015, for all indications of its reference product, Amgen's Neupogen.

This biosimilar is primarily used to treat neutropenia in cancer patients undergoing chemotherapy, demonstrating its efficacy in managing a common side effect of cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Totality of the evidence at work: The first U.S. biosimilar. Holzmann, J., Balser, S., Windisch, J.[2022]

NMR spectroscopy can effectively assess the three-dimensional structure of filgrastim (Neupogen®), providing detailed insights into its conformation and stability, particularly under varying pH conditions.

The study found that polysorbate, a common excipient, does not significantly interact with filgrastim, allowing for accurate structural analysis, which is crucial for ensuring the quality and comparability of biosimilar versions of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring Effects of Excipients, Formulation Parameters and Mutations on the High Order Structure of Filgrastim by NMR. Aubin, Y., Hodgson, DJ., Thach, WB., et al.[2018]

Triplet regimens including lenalidomide and dexamethasone show effectiveness for high-risk smoldering multiple myeloma, but more long-term follow-up is necessary to confirm these results.

For newly diagnosed multiple myeloma patients, carfilzomib- and daratumumab-based combinations are promising as safe and effective induction treatments, while maintenance therapy with ixazomib significantly prolongs progression-free survival compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. Terpos, E., Ntanasis-Stathopoulos, I.[2020]

Patients with multiple myeloma who do not respond to existing therapies have limited survival, but new treatments like CAR T-lymphocytes, bispecific antibodies, and antibody-drug conjugates are showing promise in early trials.

Idecabtagene vicleucel (ide cel) and belantamab mafodotin (belamaf) have been approved for use in relapsed/refractory multiple myeloma based on positive results from phase 2 studies, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update. Lakshman, A., Kumar, SK.[2022]

In a study of 52 patients treated with idecabtagene vicleucel (ide-cel) for relapsed/refractory multiple myeloma, 65% experienced grade ≥ 3 cytopenias by day 30, indicating significant blood cell reductions, which required interventions like G-CSF and transfusions for many patients.

Infections were reported in 54% of patients, with 23% being severe; early infections were mostly bacterial, while later infections included both bacterial and viral types, highlighting the need for careful monitoring and management of infections post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. Logue, JM., Peres, LC., Hashmi, H., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) has been approved by the FDA as a fifth-line treatment option for patients with relapsed or refractory multiple myeloma, marking a significant advancement in therapy options for this challenging condition.

Cilta-cel is notable for being the second chimeric antigen receptor T-cell therapy targeting BCMA to receive regulatory approval within a year, highlighting the rapid development of innovative treatments in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilta-cel OK'd for Multiple Myeloma. [2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Pegfilgrastim; a neutrophil mediated granulocyte colony stimulating factor-expanding uses in cancer chemotherapy. [2022]

2. England pubmed.ncbi.nlm.nih.gov

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Totality of the evidence at work: The first U.S. biosimilar. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Comparison of the pharmacodynamic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Mobilization of Hematopoietic Stem Cells into Peripheral Blood for Autologous Transplantation Seems Less Efficacious in Poor Mobilizers with the Use of a Biosimilar of Filgrastim and Plerixafor: A Retrospective Comparative Analysis. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Monitoring Effects of Excipients, Formulation Parameters and Mutations on the High Order Structure of Filgrastim by NMR. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

PF-06881893 (Nivestym™), a Filgrastim Biosimilar, Versus US-Licensed Filgrastim Reference Product (US-Neupogen®): Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of Single or Multiple Subcutaneous Doses in Healthy Volunteers. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Emerging immune targets for the treatment of multiple myeloma. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Cilta-cel OK'd for Multiple Myeloma. [2022]