Quadruple Therapy for Multiple Myeloma

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Antibiotics, Antivirals, Antifungals

Disqualifiers: Amyloidosis, Plasma cell leukemia, 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: 12-24 cycles

47 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a combination of a special antibody and three drugs to treat newly diagnosed Multiple Myeloma patients who need chemotherapy. The treatment helps the immune system find and kill cancer cells while also using drugs to stop cancer growth.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have participated in another investigational study within 3 weeks or 5 drug half-lives before starting this trial. It's best to discuss your current medications with the study team.

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

Research shows that a similar quadruple drug combination, including elotuzumab, carfilzomib, lenalidomide, and dexamethasone, has been associated with improved progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in newly diagnosed multiple myeloma patients compared to triplet regimens. ^{1 2 3 4 5}

Is the quadruple therapy for multiple myeloma safe?

The combination of carfilzomib, lenalidomide, and dexamethasone has been studied for safety in multiple myeloma patients, showing manageable side effects like low blood cell counts, fatigue, and high blood pressure. The safety profile is considered acceptable, and the treatment is approved in the EU and USA for patients who have had prior therapy. ^{3 4 6 7 8}

What makes the quadruple drug therapy for multiple myeloma unique?

The quadruple drug therapy for multiple myeloma, which includes carfilzomib, dexamethasone, elotuzumab, and lenalidomide, is unique because it combines a monoclonal antibody with a proteasome inhibitor, an immunomodulatory drug, and a corticosteroid, potentially improving progression-free survival compared to traditional triplet regimens. ^{1 2 3 5 9}

Research Team

Andrzej Jakubowiak, MD, PhD

Principal Investigator

University of Chicago

Eligibility Criteria

Adults with newly diagnosed, untreated multiple myeloma who need chemotherapy can join this trial. They must be fit for treatment (ECOG 0-1), not pregnant, and willing to follow birth control requirements. People with certain heart conditions, recent major surgery or therapy, severe neuropathy, or active infections cannot participate.

Inclusion Criteria

I have newly diagnosed myeloma and need chemotherapy.

Before starting treatment, you have a disease that can be measured and monitored.

Before joining the study, your recent blood tests must show certain levels: white blood cells above 2000, platelets above 75,000, a type of white blood cell called ANC above 1000, hemoglobin above 8.0, and a measure of kidney function within a certain range.

Exclusion Criteria

I have or might have Amyloidosis.

I have not taken antibiotics, antivirals, or antifungals for an infection in the last two weeks.

I currently have an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elotuzumab, carfilzomib, lenalidomide, and dexamethasone for 12-24 cycles

12-24 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Carfilzomib
• Dexamethasone
• Elotuzumab
• Lenalidomide

Trial Overview The study tests a combination of Elotuzumab, Carfilzomib, Lenalidomide and Dexamethasone in patients with multiple myeloma over 12-24 cycles. It's an open-label Phase 2 trial aiming to see how well the treatment works by measuring disease progression or patient survival.

Participant Groups

Group I: E-Rd Regimen Experimental Treatment 3 Interventions

Participants will receive elotuzumab, lenalidomide, and dexamethasone.

Group II: E-KRd regimen Experimental Treatment 4 Interventions

Participants will receive elotuzumab, carfilzomib, lenalidomide, and dexamethasone.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

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

Multiple Myeloma Research Foundation

Collaborator

Trials

11

Recruited

3,600+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

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]

In a study involving 792 patients with relapsed multiple myeloma, the combination of carfilzomib with lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 26.3 months compared to 17.6 months for the control group.

The carfilzomib group also showed a higher overall response rate (87.1% vs. 66.7%) and better health-related quality of life, indicating a favorable risk-benefit profile despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. Stewart, AK., Rajkumar, SV., Dimopoulos, MA., et al.[2022]

In the ENDURANCE trial involving patients with newly diagnosed multiple myeloma, the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) did not improve progression-free survival compared to the standard treatment of bortezomib, lenalidomide, and dexamethasone (VRd).

These findings suggest that KRd may not be a more effective treatment option than the current standard of care for patients with NDMM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triplet Fails to Induce Superior PFS in Newly Diagnosed Multiple Myeloma. Skarzynski, J.[2021]

Carfilzomib, when used in combination with lenalidomide and dexamethasone, significantly prolongs progression-free survival (PFS) by 8.7 months in patients with relapsed multiple myeloma, based on results from the phase III ASPIRE study involving a multinational patient population.

The combination therapy has a manageable safety profile, with low incidences of severe adverse events, suggesting it is a viable treatment option for patients who have received prior therapies, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. Hoy, SM.[2018]

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]

Carfilzomib, when combined with lenalidomide and dexamethasone, significantly improved progression-free survival (PFS) in patients with relapsed multiple myeloma, with a median PFS of 26.3 months compared to 17.6 months for the control group, indicating a clinically meaningful benefit.

The safety profile of carfilzomib was deemed manageable, with common side effects including neutropenia and anemia, suggesting that the benefits of this treatment outweigh the risks for patients who have received prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Carfilzomib for the Treatment of Adult Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy. Tzogani, K., Camarero Jiménez, J., Garcia, I., et al.[2018]

In the phase 3 CANDOR study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, daratumumab, and dexamethasone (KdD) demonstrated a significantly longer median progression-free survival of 28.6 months compared to 15.2 months for carfilzomib and dexamethasone (Kd), indicating KdD's potential as a new standard-of-care treatment.

While KdD showed improved efficacy, it was associated with a higher incidence of grade 3 or worse treatment-emergent adverse events (87% in KdD vs. 76% in Kd), including thrombocytopenia and pneumonia, highlighting the need for careful monitoring of patients receiving this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Usmani, SZ., Quach, H., Mateos, MV., et al.[2022]

In a phase 3 study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, dexamethasone, and daratumumab (KdD) significantly improved progression-free survival compared to carfilzomib and dexamethasone alone (Kd), with a hazard ratio of 0.63, indicating a 37% reduction in the risk of disease progression.

Despite a higher incidence of grade 3 or higher adverse events in the KdD group (82%) compared to the Kd group (74%), the overall safety profile was considered favorable, with similar rates of treatment discontinuation due to adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Dimopoulos, M., Quach, H., Mateos, MV., et al.[2020]

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]

References

1. 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]

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

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

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

Carfilzomib Triplet Fails to Induce Superior PFS in Newly Diagnosed Multiple Myeloma. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. [2018]

5. 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]

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

The European Medicines Agency Review of Carfilzomib for the Treatment of Adult Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. [2020]

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

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