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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of four drugs to treat multiple myeloma, a type of blood cancer that has returned or stopped responding to previous treatments. The trial combines two study drugs, carfilzomib (Kyprolis) and daratumumab (Darzalex), with two standard drugs, pomalidomide and dexamethasone, to evaluate their combined effectiveness. It seeks participants previously treated for multiple myeloma who have experienced a return or resistance of the disease. Those who have had multiple myeloma that returned or resisted treatment, and have been treated with lenalidomide and a proteasome inhibitor, might be a good fit for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Research has shown that the combination of daratumumab, carfilzomib, pomalidomide, and dexamethasone is generally well-tolerated by patients. In past studies involving individuals with multiple myeloma, the most common side effects included tiredness, pneumonia, and respiratory infections. These side effects are typical for treatments targeting multiple myeloma.

Daratumumab, an FDA-approved drug for multiple myeloma when combined with other medications, is generally safe. Carfilzomib and pomalidomide are also common treatments for this condition and are usually well-tolerated when used with other drugs.

Overall, while side effects can occur, this combination has been used safely in patients similar to those in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for multiple myeloma because it brings together four powerful drugs—daratumumab, carfilzomib, pomalidomide, and dexamethasone—that target the cancer in different ways. Daratumumab is an antibody that directly attacks myeloma cells, while carfilzomib is a proteasome inhibitor that disrupts the cancer cell's waste management system, leading to cell death. Pomalidomide modulates the immune system to fight the cancer, and dexamethasone reduces inflammation and kills myeloma cells. This multi-pronged approach could potentially overcome resistance to standard therapies and improve patient outcomes.

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

Research has shown that a combination of the drugs daratumumab, carfilzomib, pomalidomide, and dexamethasone may effectively treat relapsed and refractory multiple myeloma, a type of blood cancer. In this trial, participants will receive this combination therapy. Daratumumab, when used with pomalidomide and dexamethasone, is already approved for treating multiple myeloma, indicating its effectiveness. Carfilzomib attacks and destroys myeloma cells, making it a strong option in combination treatments. Patients who have used these drugs together have experienced better outcomes, such as longer periods without cancer progression. Overall, strong evidence supports the effectiveness of this drug combination for treating multiple myeloma. ^{1 2 3 4 6}

Who Is on the Research Team?

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. darzalexhcp.com darzalexhcp.com/indications-and-dosing/

Indications & Dosing DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma: In combination with bortezomib, ...

2. darzalex.com darzalex.com/dvrd/

DARZALEX & DARZALEX FASPRO® (daratumumab and ... An FDA-approved treatment combination for patients who are newly diagnosed with multiple myeloma and eligible to receive a stem cell transplant.

3. bloodcancerunited.org bloodcancerunited.org/resources/newsroom/fda-approval-new-treatment-indication-multiple-myeloma-drug

New Treatment Indication for Multiple Myeloma Drug The most common adverse drug reactions in patients treated with daratumumab plus hyaluronidase were fatigue, pneumonia, upper respiratory tract infection and ...

4. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/use-of-darzalex-darzalex-faspro-in-combination-with-pomalidomide-and-dexamethasone-in-multiple-myel

DARZALEX FASPRO® (daratumumab and hyaluronidase- ... APOLLO is a phase 3 study evaluating the safety and efficacy of DARZALEX FASPRO for subcutaneous (SC) use + pomalidomide + dexamethasone (D-Pd) ...

5. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... C90.02. Multiple myeloma [covered for Darzalex or Darzalex Faspro when used in combination with carfilzomib, pomalidomide and dexamethasone] [ not covered for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6676132/

Daratumumab plus carfilzomib and dexamethasone in ... This phase 1b study evaluated daratumumab plus carfilzomib and dexamethasone (D-Kd) in patients with RRMM after 1 to 3 prior lines of therapy.