Quadruple Therapy for Multiple Myeloma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of four medications for treating newly diagnosed multiple myeloma, a type of blood cancer. The medications include Carfilzomib (Kyprolis), Dexamethasone (Decadron, Dexone, Hexadrol), Elotuzumab (Empliciti), and Lenalidomide (Revlimid). The goal is to determine the effectiveness of this combination in achieving a strong cancer response and extending the period patients remain cancer-free. Individuals recently diagnosed with multiple myeloma who need chemotherapy but have not yet received full treatment may be suitable candidates. The trial also examines the treatment's safety and long-term outcomes for participants. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in multiple myeloma treatment.

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.

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

Research has shown that the combination of four drugs—elotuzumab, carfilzomib, lenalidomide, and dexamethasone, known as the Elo-KRd regimen—is generally well-tolerated. One study found that this treatment helped patients with multiple myeloma achieve deep remission, with no signs of cancer detected. Another study demonstrated its effectiveness and safety, even for patients who had tried many other treatments. While some side effects, such as tiredness and fever, can occur, they are usually manageable. Overall, evidence suggests that this regimen is safe for people with multiple myeloma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for Multiple Myeloma?

Researchers are excited about the quadruple therapy of Carfilzomib, Dexamethasone, Elotuzumab, and Lenalidomide for multiple myeloma because it offers a potentially more targeted and effective approach compared to standard treatments like bortezomib-based therapies. This combination uses Elotuzumab, a monoclonal antibody that specifically targets the SLAMF7 protein on myeloma cells, enhancing the immune system's ability to attack the cancer. Additionally, the therapy includes Carfilzomib, a next-generation proteasome inhibitor that may be more effective and cause fewer side effects than older drugs. This tailored approach not only aims to improve outcomes but also monitors patients closely for minimal residual disease, allowing for personalized treatment adjustments.

What evidence suggests that this quadruple therapy might be an effective treatment for Multiple Myeloma?

Research shows that the Elo-KRd treatment, which participants in this trial will receive, includes the drugs carfilzomib, dexamethasone, elotuzumab, and lenalidomide. This combination is promising for treating multiple myeloma, a type of blood cancer. Studies have found that adding elotuzumab to the KRd combination significantly increases the chances of deep remission, making the cancer harder to detect. Other research indicates that the combination of carfilzomib, lenalidomide, and dexamethasone helps patients with relapsed or hard-to-treat multiple myeloma live longer. Elotuzumab has also been effective in treating relapsed cases when used with other drugs. Overall, this treatment combination has shown strong response rates and is safe for patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Andrzej Jakubowiak, MD, PhD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Elo-KRd regimen Experimental Treatment 4 Interventions

Subjects will be tested for Minimal Residual Disease (MRD) by Next Generation Sequencing (NGS) and flow cytometry after cycles 8 and 12. A treatment decision was made after cycle 12 based on these results. There are three outcomes based on the IFM trial (Avet-Loiseau et al., 2015): 1) if the subject is MRD-negative by NGS after cycle 8 and 12, the subject went on E-Rd maintenance until disease progression. 2) If the subject is MRD-positive after cycle 8 but MRD-negative after cycle 12, 6 more cycles of E-KRd was given and at the end of 18 cycles, the subject went on E-Rd maintenance until disease progression. 3) Finally, if the subject is MRD-positive at both instances, 12 additional cycles of E-KRd was given and at the end of 24 cycles total, the subject went on E-Rd maintenance until disease progression.

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

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9657308/

Real-World Use and Effectiveness of Carfilzomib Plus ... Here, we describe the results for 271 patients who received carfilzomib and dexamethasone (Kd). The overall response rates (ORR) with Kd treatment were high, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8000

Carfilzomib, lenalidomide, and dexamethasone (KRd) ... In this study, the addition of elotuzumab to KRd significantly improved the rate of early, deep (≥ VGPR) MRD-negative remission in TE NDMM.

3. haematologica.org haematologica.org/article/view/haematol.2024.285534

Superior outcomes and high-risk features with carfilzomib ... Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03361306

NCT03361306 | LCI-HEM-MYE-CRD-002: Carfilzomib- ... The study drug elotuzumab, has been clinically shown to be effective in treating relapsed/refractory MM in combination with either bortezomib, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025001533

Original Study Real-World Use of carfilzomib-lenalidomide ... Carfilzomib administered as either KRd or Kd was effective and well tolerated, even in patients with multiple prior LOTs, confirming the safety and response ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37127471/

A Clinical and Correlative Study of Elotuzumab ... This phase II study combined elotuzumab (Elo) with carfilzomib, lenalidomide, and dexamethasone (KRd) for treatment of MM in first relapse with the aim of ...

7. ashpublications.org ashpublications.org/blood/article/138/Supplement%201/2739/481388/Phase-II-Trial-of-Elotuzumab-in-Combination-with

Phase II Trial of Elotuzumab in Combination with Carfilzomib ... Here, we report the preliminary results of a phase II study of Elo in combination with KRd (Elo-KRd) for MM in first relapse [ClinicalTrials.gov ...