GPC-100 + Propranolol for Multiple Myeloma

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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, open-label study. Patients will be screened within 28 days prior to the study drug administration. 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 arms: * GPC-100 in combination with propranolol; or * 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 II (BOP2) design to enroll patients for each arm. All patients will receive via IV 3.14 mg/kg GPC-100 (Burixafor) at least 2 hours prior to leukapheresis sessions from Days 7-8 (Days 9-11 optional) and 30 mg propranolol (3 x 10 mg tablets) twice daily at 8:30 AM (+/- 1 hr) and 4:00 PM (+/- 1 hr) local time from Days 1 to 8 (and on Days 9-11, if applicable). Patients will administer the first dose of propranolol onsite on Day 1. Patients will be provided with doses of propranolol for self-administration at time points when they are not otherwise required to be onsite. Sites should contact patients via telephone to confirm propranolol administration for doses administered outside of clinic.

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.

What data supports the effectiveness of the treatment GPC-100 + Propranolol for Multiple Myeloma?

The research indicates that autologous stem cell transplantation (ASCT) is a standard and effective treatment for multiple myeloma, improving response rates and survival outcomes. This suggests that the combination of GPC-100 + Propranolol, which includes ASCT, may also be effective for this condition. ^{1 2 3 4 5}

Is the treatment GPC-100 + Propranolol for Multiple Myeloma safe for humans?

The safety of autologous stem cell transplants (ASCT) for multiple myeloma has been well-established, with outpatient programs demonstrating feasibility and safety. However, specific safety data for the combination of GPC-100 and Propranolol in humans is not provided in the available research. ^{1 6 7 8 9}

What makes the GPC-100 + Propranolol treatment for multiple myeloma unique?

The combination of GPC-100 and Propranolol for multiple myeloma is unique because it pairs a novel drug (GPC-100) with Propranolol, a beta-blocker typically used for heart conditions, potentially offering a new approach to enhance the effectiveness of autologous stem cell transplants (ASCT), which are already a standard treatment for this condition. ^{1 3 6 7 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

References

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

Outpatient Autologous Stem Cell Transplants for Multiple Myeloma: Analysis of Safety and Outcomes in a Tertiary Care Center. [2020]

2. Germany 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. [2023]

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

Survival and response deepening after autologous transplantation in patients with multiple myeloma in Chile. [2022]

4. Poland pubmed.ncbi.nlm.nih.gov

Comparison of single and double autologous stem cell transplantation in multiple myeloma patients. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Autologous peripheral blood progenitor cell transplantation for multiple myeloma. [2020]

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

The Burden in Caregivers of Multiple Myeloma Patients Undergoing Outpatient Autologous Stem-Cell Transplantation Compared to Inpatient Transplantation. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Risk Factors and Outcomes of Stem Cell Mobilization Failure in Multiple Myeloma Patients. [2023]

8. Italy 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. [2023]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Severe autologous GVHD after hematopoietic progenitor cell transplantation for multiple myeloma. [2010]