BL-8040 + G-CSF for Multiple Myeloma

(GENESIS Trial)

Not currently recruiting at 25 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new treatment combination of BL-8040 (an experimental treatment) and G-CSF (a growth factor) can help mobilize stem cells for people with multiple myeloma, a type of blood cancer. Researchers aim to determine if this combination is safer and more effective than using G-CSF with a placebo. The study is double-blind, so neither participants nor researchers know who receives the actual treatment or the placebo. Ideal participants have confirmed multiple myeloma, are eligible for a stem cell transplant, and have recently completed certain types of chemotherapy. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of BL-8040 and G-CSF is generally well-tolerated by patients. Earlier studies found this treatment effective in mobilizing stem cells, which is crucial for certain medical procedures.

Safety information from these studies indicates that while some patients experienced side effects after starting treatment, these were usually manageable. Common side effects included injection site reactions and mild to moderate bone pain, typical with G-CSF treatments.

These studies reveal no signs of serious safety issues, suggesting the treatment is safe for most patients. However, as with any medical treatment, individual experiences may differ, so discussing any concerns with the clinical trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Most treatments for multiple myeloma focus on chemotherapy, targeted therapy, or immunotherapy. However, BL-8040 is unique because it targets the CXCR4 receptor, which plays a crucial role in the retention of stem cells in the bone marrow. This mechanism is different from traditional treatments and is thought to enhance stem cell mobilization, which is vital for successful stem cell transplants. Researchers are excited about this approach because it could potentially improve the effectiveness of stem cell mobilization compared to current options, possibly leading to better transplantation outcomes for patients.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

In this trial, participants will receive either BL-8040 combined with G-CSF or a placebo combined with G-CSF. Research has shown that using BL-8040 with G-CSF could aid in treating multiple myeloma. G-CSF, a growth factor, increases white blood cell production, crucial for patients undergoing chemotherapy. Combining BL-8040 with G-CSF has proven effective in helping patients gather the stem cells needed for transplants. In one study, patients who received both BL-8040 and G-CSF collected more stem cells than those who received a placebo with G-CSF. This suggests that this treatment could improve outcomes for patients needing stem cell transplants. ^{1 3 4 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

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

Underlying medical condition that would preclude study participation

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03246529

Study Details | NCT03246529 | A Phase III, Safety, ... 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 ...

2. withpower.com withpower.com/trial/phase-3-multiple-myeloma-2018-b8ff2

BL-8040 + G-CSF for Multiple Myeloma (GENESIS Trial) Research shows that G-CSFs like Filgrastim (Neupogen) are effective in reducing chemotherapy-induced neutropenia (low white blood cell count) in cancer patients ...

3. nature.com nature.com/articles/s41591-023-02273-z

Motixafortide and G-CSF to mobilize hematopoietic stem ... Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/217159Orig1s000IntegratedR.pdf

217159Orig1s000 - accessdata.fda.gov Tolerability and Efficacy of Combination Treatment of BL-8040 and G-CSF as compared to ... combination with G-CSF to 12 subjects with MM ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31495201/

Phase III trial evaluating BL-8040 + G-CSF to mobilize ... The study objective is to evaluate the superiority of one dose of BL-8040 plus G-CSF over placebo plus G-CSF to mobilize ≥6.0 × 106 CD34+ cells/ ...

6. astctjournal.org astctjournal.org/article/S1083-8791(18)31473-3/fulltext

Genesis - a Phase III Randomized Double-Blind, Placebo ... This study aims to evaluate the efficacy of single dose BL-8040 plus G-CSF in mobilization of ≥6.0 × 10 6 CD34+ cells/kg in up to 2 apheresis sessions for auto ...

7. ir.biolinerx.com ir.biolinerx.com/node/11431/pdf

BioLineRx Announces Successful Engraftment Data From ... Results so far show that mobilizing HSCs with a single BL-8040 dose combined with G-CSF is highly effective compared to using G-CSF alone, which ...