Quad Therapy for Multiple Myeloma

Recruiting at 2 trial locations

Overseen By Andrew Yee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Andrew Yee, MD

Must be taking: Acetylsalicylic acid

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, HIV, Hepatitis B, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

43 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying the combination of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in people with relapsed and refractory multiple myeloma. Relapsed and Refractory Multiple Myeloma is the condition of returned or previous treatment resistant Multiple Myeloma. This research study involves two study drugs and two standard of care drugs. * The names of the study drugs involved in this study are: * Carfilzomib * Daratumumab * The names of the standard of care drugs involved in this study are: * Dexamethasone * Pomalidomide

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on high-dose corticosteroids or any other investigational agents. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination used in the Quad Therapy for Multiple Myeloma?

Research shows that pomalidomide combined with low-dose dexamethasone is effective for patients with relapsed and refractory multiple myeloma, improving survival rates and response to treatment. Carfilzomib, another component of the therapy, has also shown significant activity in similar patient groups, indicating that these drugs can be effective in treating multiple myeloma. ^{1 2 3 4 5}

Is Quad Therapy for Multiple Myeloma safe for humans?

Research shows that Quad Therapy, which includes drugs like carfilzomib, pomalidomide, dexamethasone, and sometimes daratumumab, is generally well-tolerated in patients with relapsed or refractory multiple myeloma. Common side effects include low blood cell counts, fatigue, and infections, but serious side effects are rare. Overall, the treatment is considered safe for use in humans with this condition. ^{1 5 6 7 8}

What makes the Quad Therapy for Multiple Myeloma unique?

The Quad Therapy for Multiple Myeloma is unique because it combines four different types of drugs: carfilzomib (a proteasome inhibitor), daratumumab (a monoclonal antibody), dexamethasone (a steroid), and pomalidomide (an immunomodulatory drug). This combination aims to enhance treatment effectiveness by targeting the cancer cells in multiple ways, potentially offering a more comprehensive approach compared to traditional treatments that use fewer drugs. ^{6 9 10 11 12}

Research Team

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults aged 18-80 with relapsed or treatment-resistant multiple myeloma, who have undergone specific prior therapies and show disease progression. Participants must be able to take oral medication, have adequate organ function, agree to use birth control if applicable, and not have a history of significant illness or recent major treatments that could interfere with the study.

Inclusion Criteria

Agreement to use birth control if sexually active and not sterile

My multiple myeloma has returned or didn't respond to treatment and has gotten worse.

I can swallow pills without any issues.

Exclusion Criteria

I do not have severe nerve damage, severe allergies, or a recent stem cell transplant.

I have used specific treatments and steroids for my condition.

I do not have any health or social issues that would affect my participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab, carfilzomib, pomalidomide, and dexamethasone on a 28-day schedule

28 days per cycle

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Progression-free survival and minimal residual disease status are monitored

Up to 60 months

Treatment Details

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Pomalidomide

Trial Overview The study is testing a combination of two investigational drugs (Carfilzomib and Daratumumab) with two standard care medications (Dexamethasone and Pomalidomide) in patients with multiple myeloma that has returned after treatment or hasn't responded to previous therapy.

Participant Groups

Group I: Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone Experimental Treatment 4 Interventions

Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Participants will receive daratumumab, carfilzomib, pomalidomide, and dexamethasone on a 28 day schedule. * Daratumumab will be given according to cycle and dosage determined by protocol. * Carfilzomib will be given at 56 mg/m2 on days 1, 8, 15 (except for C1D1 where it is 20 mg/m2) * Pomalidomide will be given daily on days 1-21. * Dexamethasone will be given weekly, split over two days.

Carfilzomib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Andrew Yee, MD

Lead Sponsor

Trials

2

Recruited

50+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

The STRATUS study, involving 682 patients with relapsed and/or refractory multiple myeloma, demonstrated that the combination of pomalidomide and low-dose dexamethasone resulted in a 32.6% overall response rate, indicating its efficacy in this difficult-to-treat population.

The treatment was generally well tolerated, with the most common severe side effects being hematologic issues like neutropenia and anemia, but serious complications like venous thromboembolism were rare, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Dimopoulos, MA., Palumbo, A., Corradini, P., et al.[2021]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

Carfilzomib (CFZ) is an effective second-generation proteasome inhibitor approved for treating relapsed and refractory multiple myeloma, showing promising results even in patients with renal insufficiency and no significant impact from cytogenetic abnormalities.

Pomalidomide (POM) is a novel immunomodulatory drug with strong anti-myeloma effects, approved for patients who have not responded to previous therapies, and it has demonstrated high efficacy in those with high-risk cytogenetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs in multiple myeloma - role of carfilzomib and pomalidomide. Jurczyszyn, A., Legieć, W., Helbig, G., et al.[2021]

Four new agents have been approved for treating relapsed/refractory multiple myeloma, including bortezomib, lenalidomide, thalidomide, and liposomal doxorubicin, but there is no standard treatment, making personalized therapy essential.

New agents like carfilzomib and pomalidomide are being studied for their effectiveness and side effects, highlighting the importance of understanding treatment-related adverse events in choosing the best therapy for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. Vij, R.[2017]

The QUAD regimen, combining carfilzomib, lenalidomide, vorinostat, and dexamethasone, was found to be feasible and showed promising anti-multiple myeloma activity in a phase I study with 17 patients, achieving an overall response rate of 53%.

No dose-limiting toxicities were observed, indicating a favorable safety profile, although common grade ≥3 adverse events included neutropenia and thrombocytopenia, suggesting careful monitoring is needed during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Vesole, DH., Bilotti, E., Richter, JR., et al.[2022]

The novel combination therapy of carfilzomib, pomalidomide, and dexamethasone (CPD) was found to be well-tolerated and highly active in treating patients with relapsed and refractory multiple myeloma, with a total of 32 patients enrolled in the study.

The maximum tolerated dose (MTD) was established at carfilzomib 20/27 mg/m², pomalidomide 4 mg, and dexamethasone 40 mg, although hematologic adverse events were common, affecting over 60% of patients, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Shah, JJ., Stadtmauer, EA., Abonour, R., et al.[2022]

The combination of carfilzomib, pomalidomide, and dexamethasone (KPd) showed a high overall response rate of 79% in patients with relapsed/refractory multiple myeloma, indicating its efficacy as a treatment option.

Adding daratumumab to the KPd regimen (Dara-KPd) resulted in even better outcomes, with an overall response rate of 89% and a significant rate of measurable residual disease negativity, suggesting that Dara-KPd may provide deeper and more durable responses without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. Derman, BA., Zonder, J., Reece, D., et al.[2023]

In a phase 2 study involving 46 patients with newly diagnosed multiple myeloma, the quadruplet regimen of elotuzumab, carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) achieved a stringent complete response (sCR) and/or measurable residual disease (MRD)-negativity rate of 58% after 8 cycles, indicating significant efficacy without the need for autologous stem cell transplant (ASCT).

The study demonstrated a 3-year progression-free survival (PFS) rate of 72% overall, and an impressive 92% for patients who achieved MRD-negativity, suggesting that MRD-guided therapy could allow for reduced treatment exposure while maintaining effective outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. Derman, BA., Kansagra, A., Zonder, J., et al.[2023]

The combination therapy of daratumumab, carfilzomib, lenalidomide, and dexamethasone (D-KRd) was well tolerated in a study of 22 patients with newly diagnosed multiple myeloma, with a high overall response rate of 95%.

Most treatment-emergent adverse events were mild, with the most common being diarrhea and lymphopenia, and infusion-related reactions were primarily mild, indicating a favorable safety profile for D-KRd therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab Plus Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma. Jakubowiak, A., Usmani, SZ., Krishnan, A., et al.[2022]

Recent advancements in multiple myeloma treatment have introduced several new agents, including pomalidomide, carfilzomib, ixazomib, panobinostat, elotuzumab, and daratumumab, which have transformed treatment strategies over the past five years.

These new agents can be used in various combinations, such as doublets or triplets, and are also integrated into intensive treatment plans involving autologous stem cell transplantation, enhancing the overall management of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat myeloma with new agents. Moreau, P.[2021]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

References

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

Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. [2021]

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

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]

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

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]

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

New drugs in multiple myeloma - role of carfilzomib and pomalidomide. [2021]

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

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma. [2022]

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

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. [2022]

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

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. [2023]

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

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. [2023]

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

Daratumumab Plus Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma. [2022]

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

How I treat myeloma with new agents. [2021]

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

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]