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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals recently diagnosed with multiple myeloma, a type of blood cancer. It evaluates the safety and effectiveness of carfilzomib (also known as Kyprolis) combined with dexamethasone, and later with other drugs like clarithromycin and lenalidomide. The goal is to determine if these drugs together can better manage the disease. Individuals with confirmed multiple myeloma who have not yet started treatment might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapies.

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.

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

Research shows that using carfilzomib with dexamethasone is generally safe for patients newly diagnosed with multiple myeloma. Studies have found that this combination is well-tolerated, and many patients experience positive results. Specifically, reports indicate that carfilzomib and dexamethasone together are safe and effective.

When clarithromycin and lenalidomide are added to the treatment, most patients still tolerate it well. This combination of drugs has demonstrated lasting effectiveness, continuing to work well over time. However, like any treatment, side effects can occur, so discussing these with a healthcare provider is important. Overall, evidence supports that this treatment is safe for those newly diagnosed with multiple myeloma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Car-BiRD therapy for multiple myeloma because it combines several powerful drugs, including Carfilzomib, which targets and breaks down proteins crucial for cancer cell survival. Unlike most standard treatments that might rely on a single approach, this combination therapy uses Carfilzomib along with Clarithromycin, Lenalidomide, and Dexamethasone to attack the cancer on multiple fronts. By doing so, it has the potential to be more effective than existing treatments like Bortezomib-based therapies, offering hope for better outcomes in patients with this challenging condition.

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

Research has shown that Car-BiRD therapy, which includes carfilzomib, clarithromycin, lenalidomide, and dexamethasone, holds promise for treating multiple myeloma. In this trial, participants will receive the Car-BiRD combination. Studies have found that carfilzomib, when combined with lenalidomide and dexamethasone, improves patient outcomes. Carfilzomib is already approved for patients whose multiple myeloma has returned or not responded to other treatments. Clarithromycin, an antibiotic, may help fight myeloma by reducing harmful proteins in the body. Overall, this combination has proven effective and safe for newly diagnosed patients, offering hope for better disease management. ^{3 6 7 8 9}

Who Is on the Research Team?

Ruben Niesvizky, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34424561/

Carfilzomib and dexamethasone induction with ... The sequential Car-BiRd regimen is an effective and safe approach for the upfront treatment of MM including patients unfit for transplant.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119664888

Car-Bird [Carfilzomib, Clarithromycin(Biaxin(R)), ... Carfilzomib (Cfz) synergizes with lenalidomide and dexamethasone (Len-dex) ... Cfz/Dex therapy appears safe and effective in newly diagnosed myeloma patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5901887/

Efficacy and Toxicity Profile of Carfilzomib Based ... Despite noticeable improvement in disease outcome, MM remains incurable with high rates of relapses, highlighting the unmet need for new treatment strategies.

4. nature.com nature.com/articles/s41375-019-0517-6

Carfilzomib with immunomodulatory drugs for the treatment ... Carfilzomib, a selective proteasome inhibitor (PI), is approved for the treatment of patients with relapsed or refractory multiple myeloma ...

5. healthtree.org healthtree.org/myeloma/community/podcasts/Using-Antibiotics-in-Myeloma-Combos-to

Using Antibiotics in Myeloma Combos To Kill Myelom A common antibiotic, clarithromycin (typically used for sinus infections) has been tested in myeloma and has found to help kill myeloma because it reduces ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8493667/

Efficacy and Toxicity Profile of Carfilzomib-Based Regimens ... In this review, we assess the efficacy and toxicity of CFZ-based regimens in NDMM. We reviewed a total of 27 studies (n=4538 patients) with overall response ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4390045/

Clarithromycin overcomes resistance to lenalidomide and ... The combination of clarithromycin, lenalidomide and dexamethasone (BiRd) has led to highly durable responses in newly diagnosed myeloma.

8. nature.com nature.com/articles/s41408-021-00490-8

Lenalidomide and dexamethasone with or without ... In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity.

9. kyprolis-hcp.com kyprolis-hcp.com/dosing-and-administration/safety

Long-Term Safety | KYPROLIS® (carfilzomib) Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol ...