Carfilzomib + Dexamethasone for Multiple Myeloma

(CarBiRD Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Corticosteroids, Antiresorptive therapy

Must not be taking: Antivirals, Antibacterials

Disqualifiers: HIV, Hepatitis B/C, Heart failure, 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

74 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and effectiveness of an investigational new drug called carfilzomib, in combination with dexamethasone in subjects with newly diagnosed multiple myeloma followed by treatment with a combination of drugs clarithromycin (Biaxin®), lenalidomide (Revlimid®) and dexamethasone (Decadron®) \[BiRD\] then lenalidomide alone.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had any anti-myeloma therapy within 14 days before starting the study, except for certain corticosteroids. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Carfilzomib, Lenalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that the combination of Carfilzomib, Lenalidomide, and Dexamethasone significantly improved progression-free survival in patients with relapsed multiple myeloma, offering a clinically relevant gain of 8.7 months compared to Lenalidomide and Dexamethasone alone. This combination also improved overall response rates and patients' global health status. ^{1 2 3 4 5}

What safety data exists for Carfilzomib and Dexamethasone in treating multiple myeloma?

Carfilzomib combined with dexamethasone has been studied in multiple trials for treating multiple myeloma, showing a generally manageable safety profile. Common side effects include low blood cell counts, fatigue, high blood pressure, and infections, but these are considered manageable in the context of treatment. ^{1 3 5 6 7}

How is the drug Carfilzomib + Dexamethasone for Multiple Myeloma different from other treatments?

Carfilzomib combined with dexamethasone is unique because it is a proteasome inhibitor that binds selectively and irreversibly, showing promising activity in relapsed or refractory multiple myeloma, and it has been shown to significantly prolong progression-free survival compared to lenalidomide plus dexamethasone alone. ^{1 2 3 4 8}

Research Team

Ruben Niesvizky, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who haven't had anti-myeloma therapy recently, except limited corticosteroids. Participants must have measurable disease, be able to perform daily activities at a certain level, take blood clot prevention medication, and comply with the RevAssist® program. Women of childbearing age must test negative for pregnancy and use birth control.

Inclusion Criteria

Participants must have certain test results within a certain range.

I haven't had myeloma treatment in the last 14 days, except for limited corticosteroids.

If subject is a female of childbearing potential (FCBP), she must have a negative pregnancy test and agree to specific birth control measures

Exclusion Criteria

I do not have any infections or health issues that would make this treatment too risky for me.

I am currently pregnant or breastfeeding.

My multiple myeloma cannot be measured by standard tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Car Phase

Participants receive carfilzomib in combination with dexamethasone

Approximately 23 weeks

Regular visits for drug administration and monitoring

Stem Cell Collection

Participants undergo stem cell collection at the end of the Car Phase

1 week

BiRD Phase

Participants receive clarithromycin, lenalidomide, and dexamethasone

Up to 116 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1222 days

Treatment Details

Interventions

• Carfilzomib
• Clarithromycin
• Dexamethasone
• Lenalidomide

Trial Overview The study tests carfilzomib combined with dexamethasone in new multiple myeloma patients followed by clarithromycin (Biaxin®), lenalidomide (Revlimid®), and dexamethasone [BiRD] treatment then maintenance with lenalidomide alone to assess safety and effectiveness.

Participant Groups

Group I: Car-BiRD Therapy Experimental Treatment 4 Interventions

Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) \[Car-BiRD\]

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?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Onyx Therapeutics, Inc.

Industry Sponsor

Trials

20

Recruited

1,300+

Findings from Research

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]

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]

The KRd regimen (carfilzomib, lenalidomide, and dexamethasone) demonstrated a high overall response rate of 88.5% in 26 heavily pretreated Japanese patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

While the KRd regimen was generally well tolerated, a higher incidence of hyperglycemia was noted, likely due to dexamethasone, suggesting the need for monitoring blood sugar levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan. Suzuki, K., Ri, M., Chou, T., et al.[2021]

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 study involving 929 patients with relapsed or refractory multiple myeloma, carfilzomib combined with dexamethasone significantly improved median progression-free survival (18.7 months) compared to bortezomib with dexamethasone (9.4 months), indicating greater efficacy of carfilzomib.

While both treatments had serious adverse events, carfilzomib was associated with a higher rate of serious adverse events (48%) compared to bortezomib (36%), suggesting that while carfilzomib may be more effective, it also carries a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Dimopoulos, MA., Moreau, P., Palumbo, A., et al.[2022]

References

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

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

2. France pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

Carfilzomib in addition to lenalidomide and dexamethasone in Asian patients with RRMM outside of a clinical trial. [2021]

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

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

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

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan. [2021]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Use and Effectiveness of Carfilzomib Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma in Europe. [2022]

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

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. [2022]