Motixafortide + G-CSF for Multiple Myeloma

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, motixafortide, to evaluate its effectiveness in helping people with multiple myeloma, a type of blood cancer, prepare for a stem cell transplant. The researchers aim to determine if administering motixafortide at different times affects the collection of crucial stem cells needed for the transplant. Participants will receive the treatment either at a standard time or an earlier time to compare results. Individuals with multiple myeloma who have already undergone certain chemotherapy treatments without a stem cell transplant might be suitable for this study. As a Phase 1 trial, this research focuses on understanding how motixafortide works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that motixafortide is likely to be safe for humans?

Research has shown that motixafortide has been safely used in patients with multiple myeloma. Studies have found that combining motixafortide with G-CSF (a drug that increases stem cells in the blood) is well-tolerated. In one study with healthy volunteers, motixafortide was safe and did not cause serious side effects.

Motixafortide is also approved by the FDA for use in multiple myeloma patients to assist with stem cell transplants, indicating its safety. While mild side effects may occur, as with any treatment, evidence suggests it is generally safe for patients. ^{1 2 3 4 5}

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

Unlike the standard treatments for multiple myeloma, which typically involve chemotherapy and stem cell transplants, motixafortide offers a unique approach by targeting the CXCR4 receptor. This receptor is involved in the movement and growth of cancer cells. By blocking it, motixafortide may enhance the effectiveness of stem cell mobilization, potentially leading to better outcomes in cell collection for transplants. Researchers are excited because this method could improve the efficiency and success of stem cell collection, making the transplant process smoother and possibly more successful for patients.

What evidence suggests that motixafortide + G-CSF could be an effective treatment for multiple myeloma?

This trial will evaluate motixafortide in combination with G-CSF for patients with multiple myeloma. Research has shown that motixafortide can significantly aid in stem cell collection for these patients. In one study, 92.5% of patients who received motixafortide with G-CSF collected the target amount of 6 million stem cells per kilogram. Another study found that this combination enabled 67.5% of patients to reach similar stem cell collection goals quickly, in just two sessions or less. These findings suggest that motixafortide effectively prepares multiple myeloma patients for stem cell transplants, which can help restore normal blood counts. Participants in this trial will join one of two cohorts to evaluate different dosing schedules of motixafortide. ^{2 5 6 7 8}

Who Is on the Research Team?

Zachary D Crees, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10115633/

Motixafortide and G-CSF to mobilize hematopoietic stem cells ...

In total, 98.8% (79 of 80) of patients in the motixafortide + G-CSF arm and 97.6% (41 of 42) of patients in the placebo + G-CSF arm received all ...

2.

foxchase.org

foxchase.org/news/new-protocol-reduces-side-effects-use-key-drug-multiple-myeloma-patients

New Protocol Reduces Side Effects In Use of Key Drug for ...

Fox Chase Cancer Center researchers have identified a pretreatment protocol that reduces side effects for the drug motixafortide, which is sold under the brand ...

3.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2023/motixafortide-multiple-myeloma-stem-cell-transplant

Motixafortide and Stem Cell Transplants for Multiple Myeloma

Motixafortide May Improve Stem Cell Transplants for People with Multiple Myeloma · Transplanted stem cells help restore normal blood counts.

4.

jhoponline.com

jhoponline.com/issue-archive/2023-issues/december-2023-vol-13-no-6/fda-approved-aphexda-in-combination-with-filgrastim-to-mobilize-stem-cells-for-transplant-in-patients-with-multiple-myeloma

FDA Approved Aphexda, in Combination With Filgrastim, to ...

Of the patients who received motixafortide plus filgrastim, 67.5% achieved the stem cell collection goal of ≥6 × 106 CD34+ cells/kg in ≤2 ...

5.

healthtree.org

healthtree.org/myeloma/community/articles/motixafortide-mobilizing-agent

Motixafortide Increases Stem Cell Collection

In this study, 92.5% of patients who received motixafortide plus G-CSF achieved the primary endpoint of collecting 6 × 106 CD34+ cells/kg or ...

6.

aphexda.com

aphexda.com/

FDA-Approved APHEXDA® (motixafortide)

APHEXDA + filgrastim indicated to mobilize hematopoietic stem cells to peripheral blood for autologous transplant in patients with multiple myeloma.

7.

accessdata.fda.gov

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

217159Orig1s000 - accessdata.fda.gov

The safety review focused on the GENESIS study, which included data from 92 subjects with multiple myeloma. (N=12 from part 1 of the study ...

8.

aetna.com

aetna.com/cpb/medical/data/1000_1099/1046.html

Motixafortide (Aphexda) - Medical Clinical Policy Bulletins

Aetna considers motixafortide (Aphexda) medically necessary in members with multiple myeloma when all of the following criteria are met.