GPC-100 + Propranolol for Multiple Myeloma

Not currently recruiting at 9 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GPCR Therapeutics, Inc.

Must be taking: Propranolol

Must not be taking: ACE inhibitors, Calcium blockers

Disqualifiers: Previous transplant, Severe asthma, Cardiovascular disease, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-11 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for multiple myeloma, a type of blood cancer. It examines the safety and effectiveness of the drug GPC-100 when combined with propranolol, and in some cases, an additional drug called G-CSF, which stimulates white blood cell production. Participants will be randomly assigned to one of two groups to explore these combinations. Individuals who have had multiple myeloma for some time and completed chemotherapy at least four weeks ago might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are currently taking beta blockers (a type of heart medication), you may need to switch to a different therapy and gradually taper off your current medication under the guidance of the study doctor. You cannot take certain heart medications like ACE inhibitors, calcium channel blockers, or alpha blockers while on propranolol during the study.

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

Research has shown that the combination of GPC-100 and propranolol is generally well-tolerated. In earlier studies, GPC-100 caused only mild side effects, such as flushing, chest tightness, stomach pain, and nausea. Notably, no severe side effects or cases of diarrhea were reported.

When propranolol and G-CSF are added to GPC-100, early results suggest promising outcomes. Although specific side effects for this combination aren't detailed, the findings so far are encouraging. The current phase of the trial indicates that the treatment has passed initial safety tests, but more data is being collected to confirm this.

Participants considering joining should feel reassured that existing studies report only mild side effects for these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they explore new combinations that could enhance existing therapies. Unlike standard treatments that typically involve chemotherapy or targeted therapies, GPC-100 combined with propranolol introduces a novel approach by potentially disrupting cancer cell environments and inhibiting stress responses that support tumor growth. Adding G-CSF (granulocyte-colony stimulating factor) to this mix could further boost the body’s ability to recover and maintain healthy blood cell levels after treatment. This innovative combination has the potential to improve patient outcomes by targeting multiple facets of the disease simultaneously.

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

In this trial, participants will be randomly assigned to one of two treatment arms. A previous study showed that the combination of GPC-100 and propranolol helped patients with multiple myeloma by moving more stem cells into the bloodstream, which is crucial for effective treatment. One arm of this trial will test this combination. Research suggests that adding G-CSF to this combination can further increase the number of stem cells in the blood compared to other treatments. The other arm of this trial will test the combination of GPC-100, propranolol, and G-CSF. Early findings indicate that these combinations could improve outcomes for multiple myeloma patients by aiding the recovery of healthy blood cells during treatment. Overall, these treatments have shown strong potential in early studies. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults diagnosed with Multiple Myeloma eligible for stem cell transplant, not on their first or second response to treatment. They must have normal organ function, blood pressure within specific limits, and agree to use contraception. Excluded are those with certain heart conditions, active infections, previous transplants, recent investigational drug use, severe asthma requiring beta agonists, or a positive COVID-19 test.

Inclusion Criteria

My doctor thinks I am a good candidate for a stem cell transplant.

Your white blood cell count is at least 1.0 x 10^9/L.

Your liver enzymes and bilirubin levels are within a certain range on the lab tests before the study.

Exclusion Criteria

I have a history of long QT syndrome or torsade de pointes.

I have severe asthma and need beta agonist therapy.

I have not received G-CSF treatment in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Patients receive GPC-100 and propranolol, with or without G-CSF, for stem cell mobilization

8-11 days

Daily visits for drug administration and leukapheresis

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Stem Cell Transplant
• Bayesian Optimal Phase II Design
• G-CSF
• Stem Cell Mobilization

Trial Overview The trial is testing the safety and effectiveness of GPC-100 combined with propranolol versus adding G-CSF to this combination in mobilizing stem cells for transplantation in Multiple Myeloma patients. It's randomized and open-label with two arms receiving different treatments.

How Is the Trial Designed?

Group I: GPC-100 in combination with propranolol; Experimental Treatment 2 Interventions

Patients will be randomly assigned to 1 of 2 treatment arms prior to study drug administration. Approximately 40 patients will be randomized in a 1:1 ratio to the following treatment arm: • GPC-100 in combination with propranolol; or

Group II: GPC-100 in combination with propranolol and G-CSF Experimental Treatment 3 Interventions

Patients will be randomly assigned to 1 of 2 treatment arms prior to study drug administration. Approximately 40 patients will be randomized in a 1:1 ratio to the following treatment arm: • GPC-100 in combination with propranolol and G-CSF.

Autologous Stem Cell Transplant is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Autologous Stem Cell Transplant for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Hodgkin Lymphoma
• Leukemia

Approved in European Union as Autologous Stem Cell Transplant for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Hodgkin Lymphoma
• Leukemia

Approved in Canada as Autologous Stem Cell Transplant for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Hodgkin Lymphoma
• Leukemia

Who Is Running the Clinical Trial?

GPCR Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

150+

Published Research Related to This Trial

A study of 540 patients with multiple myeloma showed that newer induction therapies like bendamustine/prednisolone (BPV) and cyclophosphamide/dexamethasone (VCD) significantly improved progression-free survival (PFS) compared to older treatments, with PFS of 47 and 54 months respectively, compared to 35 months for the older VAD regimen.

Importantly, patients who did not meet the typical exclusion criteria for transplant studies had similar outcomes in terms of PFS and overall survival (OS) compared to those who did meet the criteria, suggesting that ASCT remains a valuable treatment option for a broader range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the changing landscape of induction therapy prior to autologous stem cell transplantation in 540 newly diagnosed myeloma patients: a retrospective real-world study. Wang, SY., Holzhey, T., Heyn, S., et al.[2023]

Outpatient autologous stem cell transplant (ASCT) for multiple myeloma is a safe and effective treatment option, with a very low transplant-related mortality rate of 0.4% and overall 30-day and 100-day mortality rates of 0.9%.

In a study of 724 patients, 32.6% required inpatient admission post-transplant, with a median admission time of 6 days, indicating that while outpatient ASCT is feasible, it necessitates careful monitoring and a multidisciplinary approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient Autologous Stem Cell Transplants for Multiple Myeloma: Analysis of Safety and Outcomes in a Tertiary Care Center. Kodad, SG., Sutherland, H., Limvorapitak, W., et al.[2020]

Autologous stem cell transplantation (ASCT) using peripheral blood progenitor cells (PBPC) has become a preferred method for treating multiple myeloma (MM), offering benefits like easier access and faster recovery compared to traditional bone marrow sources.

The IFM 90 randomized trial demonstrated that ASCT significantly improves response rates, event-free survival, and overall survival in younger patients with MM, highlighting its efficacy in cases where conventional chemotherapy has failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood progenitor cell transplantation for multiple myeloma. Attal, M., Harousseau, JL.[2020]

In a study of 301 newly diagnosed multiple myeloma patients, 95% successfully collected enough hematopoietic stem cells (HSCs) for transplantation using a combination of cyclophosphamide, G-CSF, and on-demand plerixafor, demonstrating the efficacy of this mobilization strategy.

Factors such as high bone marrow plasmacytosis at diagnosis, use of lenalidomide, and severe hematologic toxicities during treatment were linked to a higher risk of poor HSC mobilization, indicating the need for careful patient assessment before stem cell collection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, multicenter study on hematopoietic stem-cell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor and 'on-demand' plerixafor in multiple myeloma patients treated with novel agents. Mina, R., Petrucci, MT., Bonello, F., et al.[2023]

In a study of multiple myeloma patients undergoing stem cell collection, low absolute monocyte count (<500/µL) and low platelet count (<150,000/µL), along with a longer time from diagnosis to stem cell harvest (≥180 days), were identified as significant risk factors for mobilization failure.

The prediction model developed in this study demonstrated high sensitivity (84.6%) and specificity (84.0%) for identifying patients at risk of poor mobilization, allowing for timely interventions to improve outcomes before autologous hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors and Outcomes of Stem Cell Mobilization Failure in Multiple Myeloma Patients. Hsu, TL., Tsai, CK., Liu, CY., et al.[2023]

In a retrospective study of multiple myeloma patients who underwent single or double autologous stem cell transplantation (ASCT) between 2003 and 2020, there was no significant difference in overall survival (OS) or progression-free survival (PFS) between the two groups, suggesting that a second ASCT may not provide additional benefits.

The study indicates that with the advent of novel anti-myeloma drugs, the necessity for a second ASCT may be reduced, as these new treatments could offer effective alternatives without the need for additional transplant procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of single and double autologous stem cell transplantation in multiple myeloma patients. Malkan, UY., Demiroglu, H., Buyukasik, Y., et al.[2022]

In a study of 50 patients undergoing autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma, the treatment significantly improved response rates, with complete responses increasing from 27.6% to 52.5% after ASCT.

The median progression-free survival (PFS) was estimated at 39 months, indicating that ASCT is an effective strategy for prolonging survival in patients with multiple myeloma, with measurable residual disease being a key predictor of PFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and response deepening after autologous transplantation in patients with multiple myeloma in Chile. Guerra, MC., Jerez, J., Godoy, G., et al.[2022]

A study comparing caregivers of multiple myeloma patients undergoing inpatient (71 participants) versus outpatient (25 participants) autologous stem-cell transplantation found no significant differences in caregiver burden, daily activities, or general health between the two groups before and three months after the procedure.

The outpatient model of care for ASCT does not appear to improve or worsen the overall burden on caregivers compared to traditional inpatient care, suggesting that both models may have similar impacts on caregiver well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Burden in Caregivers of Multiple Myeloma Patients Undergoing Outpatient Autologous Stem-Cell Transplantation Compared to Inpatient Transplantation. Martino, M., Pitino, A., Tripepi, G., et al.[2022]

Melphalan at a myeloablative dose followed by autologous stem cell transplantation (ASCT) is still considered the standard treatment for transplant-eligible patients with myeloma, indicating its established efficacy in this patient group.

Emerging therapies, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and CAR T cells, are reshaping treatment strategies, prompting a reevaluation of when and for whom ASCT should be used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are Autologous Stem Cell Transplants Still Required to Treat Myeloma in the Era of Novel Therapies? A Review from the Chronic Malignancies Working Party of the EBMT. Garderet, L., Morris, C., Beksac, M., et al.[2021]

Severe autologous graft-versus-host disease (GVHD) developed in five patients after autologous hematopoietic progenitor cell transplantation for multiple myeloma, with poor response to corticosteroid treatment leading to significant complications.

The occurrence of severe autologous GVHD was notably higher in patients undergoing a second transplantation, suggesting that repeated high-dose therapies may weaken the body's regulatory mechanisms and increase the risk of autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe autologous GVHD after hematopoietic progenitor cell transplantation for multiple myeloma. Drobyski, WR., Hari, P., Keever-Taylor, C., et al.[2010]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4858/534213/An-Open-Label-Multi-Center-Phase-2-Study-to-Assess

An Open-Label, Multi-Center Phase 2 Study to Assess the ... Propranolol, a non-selective beta-blocker, has been clinically shown to inhibit molecular risk markers in MM patients receiving ASCT. Other ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05561751?spons=COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22GPCR%20Therapeutics,%20Inc.%22)&viewType=Table&rank=1

Ph2, Study to Assess the Safety and Efficacy of GPC 100 ... GPC-100 in combination with propranolol and G-CSF. To characterize the safety and clinical activity of GPC-100, the study will employ a Bayesian Optimal Phase ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3428/499804/Combination-of-Propranolol-and-a-Novel-CXCR4

Combination of Propranolol and a Novel CXCR4 Antagonist ... Addition of propranolol to G-CSF and GPC-100 led to 8-17-fold increases in mobilization of long-term repopulating HSCs (CD34 negLSK and CD150 + ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0287863

GPC-100, a novel CXCR4 antagonist, improves in vivo ... The combination of GPC-100 and propranolol is a novel strategy for stem cell mobilization and support the current clinical trial in multiple myeloma.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10599528/

GPC-100, a novel CXCR4 antagonist, improves in vivo ... GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000649712407616X

An Open-Label, Multi-Center Phase 2 Study to Assess the ... AEs related to GPC-100 were all grade 1 and include flushing, chest tightness, stomach pain, and nausea, as observed before. No incidence of diarrhea during ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02147

Ph2, Study to Assess the Safety and Efficacy of GPC 100 ... This is a randomized, open-label study. Patients will be screened within 28 days prior to the study drug administration.