Motixafortide + G-CSF for Multiple Myeloma

Overseen By Zachary Crees, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must be taking: Daratumumab, Proteasome inhibitors, IMiDs, Dexamethasone

Must not be taking: Antidepressants, Erythropoietin, Live vaccines, others

Disqualifiers: HIV, Hepatitis B, Heart failure, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study includes extended CD34+ profiling on the apheresis product of multiple myeloma patients undergoing standard-of-care quad-induction followed by motixafortide + G-CSF mobilization, and in addition, assesses the pharmacodynamics (PD) of motixafortide following "standard" (\~12 hours) vs "early" (\~16 hours) dosing. The investigators hypothesize that quad-induction may alter the stem cell subsets within the mobilized graft. The investigators further hypothesize that standard and early dosing strategies will result in comparable mobilization and stem cell collection rates.

Will I have to stop taking my current medications?

The trial requires a 'washout' period (time without taking certain medications) for specific drugs before starting the study. You must stop taking medications like dexamethasone, thalidomide, lenalidomide, and others for at least 7 days, and some drugs like erythropoietin for up to 30 days before the trial begins.

What data supports the effectiveness of the drug Motixafortide + G-CSF for treating multiple myeloma?

In a study, Motixafortide combined with G-CSF was shown to be highly effective in helping patients with multiple myeloma collect the necessary stem cells for transplantation, with 92.5% of patients meeting the target compared to only 26.2% with a placebo. ^{1 2 3 4 5}

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

The combination of Motixafortide and G-CSF has been found to be safe and well tolerated in humans, with the most common side effects being mild and temporary reactions at the injection site, such as pain, redness, and itching. ^{2 5 6 7 8}

What makes the drug Motixafortide unique for treating multiple myeloma?

Motixafortide, when combined with G-CSF, is unique because it significantly improves the mobilization of hematopoietic stem cells (HSCs) for autologous transplantation in multiple myeloma patients, achieving higher success rates in collecting the necessary stem cells compared to G-CSF alone. This combination is particularly effective for patients who struggle to collect enough stem cells with standard treatments. ^{1 2 3 5 6}

Research Team

Zachary D Crees, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for multiple myeloma patients who are undergoing standard quad-induction therapy. They will be part of a study to see how different timing of the drug motixafortide, combined with G-CSF, affects stem cell collection in their treatment.

Inclusion Criteria

It has been at least 7 days since my last treatment before starting G-CSF for stem cell collection.

Ability to understand and sign an IRB approved informed consent document

My organs are working well.

Exclusion Criteria

I have been treated with radioimmunotherapy or venetoclax before.

I have received more than 8 cycles of chemotherapy with alkylating agents.

History of allergic reactions to study compounds

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Quad-induction

Participants undergo standard-of-care quad-induction therapy

4-8 weeks

Mobilization

Motixafortide + G-CSF mobilization with standard and early dosing strategies

1 week

Multiple visits for dosing and apheresis

Follow-up

Participants are monitored for safety and effectiveness after mobilization

4 weeks

Treatment Details

Interventions

• Motixafortide

Trial Overview The study tests how well motixafortide works when given at 'standard' (~12 hours) vs 'early' (~16 hours) times before collecting stem cells. It also looks at the effects of quad-induction on stem cell types in the mobilized graft from these patients.

Participant Groups

Group I: Cohort 2: Early dosing Experimental Treatment 2 Interventions

For Cohort 2, motixafortide will be given on Day 4 between 2:00 and 4:00 pm. A second dose may be given on Day 6 with goal of administration between 6:00 and 8:00 pm after completion of pheresis if clinically feasible. if CD34+ cell collection goals are not met on Day 5 apheresis.

Group II: Cohort 1: Standard dosing Active Control 2 Interventions

For Cohort 1, motixafortide will be given on Day 4 between 6:00 and 8:00 pm. A second dose may be given on Day 6 between 6:00 and 8:00 p.m. if CD34+ cell collection goals are not met on Day 5 apheresis.

Motixafortide is already approved in United States for the following indications:

Approved in United States as Aphexda for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

BioLineRx, Ltd.

Industry Sponsor

Trials

24

Recruited

2,200+

Arvrmid Pharma

Collaborator

Trials

1

Recruited

20+

Findings from Research

In a study of 41 multiple myeloma patients, the combination of plerixafor (PXF) and granulocyte colony-stimulating factor (G-CSF) resulted in a higher number of collected CD34+ cells and a greater acquisition success rate compared to cyclophosphamide (Cy) and G-CSF.

The PXF+G-CSF regimen not only led to better mobilization outcomes but also reduced the risk of infections and shortened hospital stays, although it did come with increased costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma]. Li, WT., Ma, LM., Lian, Y., et al.[2023]

In the GENESIS trial involving 122 adult patients with multiple myeloma, the combination of motixafortide and G-CSF significantly improved the collection of CD34+ hematopoietic stem and progenitor cells (HSPCs) for autologous stem cell transplantation, achieving a success rate of 92.5% compared to only 26.2% with placebo plus G-CSF.

Motixafortide was found to be safe and well tolerated, with mostly mild and transient side effects, indicating its potential as an effective and safe option for enhancing HSPC mobilization in patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. Crees, ZD., Rettig, MP., Jayasinghe, RG., et al.[2023]

Plerixafor combined with G-CSF effectively mobilizes hematopoietic stem cells for patients with multiple myeloma, but the long-term outcomes in terms of progression-free survival (PFS) and overall survival (OS) do not show significant differences compared to other mobilization regimens.

In this study involving multiple cohorts, while G-CSF plus plerixafor (G-CSF+P) is a viable option for patients with poor mobilization, it did not demonstrate noninferiority in PFS and OS, and the cumulative incidence of relapse was higher in the plerixafor groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a multicenter, noninterventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor. Morris, C., Chabannon, C., Masszi, T., et al.[2022]

In a study of 55 newly diagnosed multiple myeloma patients, single large volume leukapheresis using either G-CSF or G-CSF plus Plerixafor successfully achieved the primary stem cell yield target of ≥2×10^6 cells per kg in all cases.

The procedure was found to be safe and cost-effective, with manageable adverse reactions, and factors such as age and pre-apheresis CD34+ count significantly influenced the stem cell yield.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective identification of potential factors influencing stem cell mobilization and the necessity for plerixafor use in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation. Ray, GK., Jena, RK., Panda, T., et al.[2021]

Novel treatments for multiple myeloma, including immunomodulating drugs and proteasome inhibitors, have significantly improved survival rates, but febrile neutropenia remains a serious side effect that can hinder treatment effectiveness.

Pegfilgrastim, a long-acting form of G-CSF, may offer advantages over traditional filgrastim by reducing the incidence of neutropenia and febrile neutropenia, allowing for more consistent chemotherapy administration and potentially being more cost-effective due to fewer required injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim for primary prophylaxis of febrile neutropenia in multiple myeloma. Cerchione, C., Nappi, D., Martinelli, G.[2022]

Motixafortide, a selective CXCR4 inhibitor, was approved in the USA on September 11, 2023, for mobilizing hematopoietic stem cells (HSCs) in combination with filgrastim for patients with multiple myeloma, marking a significant advancement in stem cell transplantation.

The drug has also received Orphan Drug Designation for treating pancreatic cancer and acute myeloid leukemia, and is being studied for mobilizing CD34+ HSCs for gene therapy in sickle cell disease, indicating its potential in various cancer treatments and therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motixafortide: First Approval. Hoy, SM.[2023]

Recombinant human granulocyte colony-stimulating factor (G-CSF) has been effectively used for about 20 years to mobilize blood cells for stem cell transplants and to reduce neutropenia in patients undergoing chemotherapy.

While G-CSF is generally considered safe, the increasing number of clinical applications has led to the recognition of more side effects, highlighting the need for awareness of its adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte colony-stimulating factor administration: adverse events. D'Souza, A., Jaiyesimi, I., Trainor, L., et al.[2019]

Pegfilgrastim significantly reduces the incidence of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) compared to no prophylaxis, with evidence from 41 studies including randomized controlled trials and observational studies.

The efficacy and safety profiles of other long-acting G-CSFs, such as lipegfilgrastim and balugrastim, are comparable to pegfilgrastim, although results for other long-acting G-CSFs were mixed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review. Pfeil, AM., Allcott, K., Pettengell, R., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma]. [2023]

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

Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. [2023]

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

Results from a multicenter, noninterventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor. [2022]

4. Brazil pubmed.ncbi.nlm.nih.gov

Prospective identification of potential factors influencing stem cell mobilization and the necessity for plerixafor use in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Pegfilgrastim for primary prophylaxis of febrile neutropenia in multiple myeloma. [2022]

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

Motixafortide: First Approval. [2023]

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

Granulocyte colony-stimulating factor administration: adverse events. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review. [2021]