MeziKD for Multiple Myeloma

Overseen By ASK RPCI

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: CYP3A modulators, Proton-pump inhibitors

Disqualifiers: Active infection, Prior malignancy, 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: 10

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs—mezigdomide, carfilzomib, and dexamethasone—to determine if they can more effectively treat multiple myeloma, a type of blood cancer that has returned or is unresponsive to treatment. The aim is to assess whether this combination can kill more cancer cells, particularly those outside the bone marrow. Suitable participants have experienced relapsed or refractory multiple myeloma and have undergone at least one prior treatment. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take strong CYP3A modulators or proton-pump inhibitors within 2 weeks of starting the study. You may continue taking bisphosphonates and low-dose corticosteroids if they are stable for at least 7 days before starting the trial.

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

Research has shown that the combination of mezigdomide, carfilzomib, and dexamethasone (MeziKD) holds promise for individuals with multiple myeloma that has returned or is unresponsive to treatment. Studies have found this combination to be generally well-tolerated. Most serious side effects, known as grade 3-4 treatment-related adverse events, are rare, except for some infections when using mezigdomide with dexamethasone and other drugs. This indicates that while risks exist, many patients do not experience severe problems.

Earlier studies of mezigdomide with dexamethasone demonstrated good responses, even after other treatments failed. The combination with carfilzomib also showed a strong response rate. This is significant because it suggests the treatment can be effective without causing many serious side effects.

For those considering joining this clinical trial, the treatment has been safely tested in humans before, with careful monitoring for any issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which typically include drugs like lenalidomide or bortezomib, Mezigdomide offers a fresh approach. It is an experimental drug featuring a novel mechanism of action that targets and degrades specific proteins within cancer cells, potentially leading to their destruction. Researchers are excited about Mezigdomide because it might work on multiple myeloma cells that are resistant to current treatments. Additionally, its combination with carfilzomib and dexamethasone, which are already effective, could enhance overall treatment efficacy and provide new hope for patients.

What evidence suggests that MeziKD might be an effective treatment for multiple myeloma?

Research shows that the combination of mezigdomide, carfilzomib, and dexamethasone (MeziKD), which participants in this trial will receive, holds promise for treating relapsed or refractory multiple myeloma (MM). Studies have found that mezigdomide with dexamethasone effectively treats heavily pretreated multiple myeloma, leading to significant improvements. Specifically, one study found that a 1.0 mg dose of mezigdomide resulted in a 60% overall response rate, with 20% of patients experiencing a very good partial response. Carfilzomib stops cancer cell growth by blocking important enzymes. Together, these drugs work to kill more cancer cells, offering hope for patients with hard-to-treat MM. ^{1 2 3 6 7}

Who Is on the Research Team?

Jens Hillengass, MD

Principal Investigator

Roswell Park Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed or refractory multiple myeloma and extramedullary disease, who've had prior treatments. They must have adequate blood counts, kidney function, liver enzymes, and heart pump function. Women of childbearing age must use contraception.

Inclusion Criteria

My platelet count is at least 75 x 10^9/L.

My total bilirubin levels are within the normal range.

My white blood cell count is within a healthy range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive mezigdomide, carfilzomib, and dexamethasone for up to 6 cycles, each cycle lasting 28 days

24 weeks

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 6 months

Extension

Participants showing a response to therapy may continue the treatment regimen as part of standard of care

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Dexamethasone
• Mezigdomide

Trial Overview The study tests MeziKD (Mezigdomide/Carfilzomib/Dexamethasone) in treating patients with stubborn multiple myeloma that has spread outside the bone marrow. It examines if this combination can more effectively kill cancer cells.

How Is the Trial Designed?

Group I: Treatment - MeziKD Experimental Treatment 10 Interventions

Patients receive mezigdomide PO QD on days 1-21 of each cycle, carfilzomib IV over 30 minutes on days 1, 8, and 15 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles of study treatment, patients showing a response to therapy may continue the treatment regimen as part of standard of care per physician's discretion. Additionally, patients undergo ECHO, PET/CT, MRI, CT guided tumor biopsy, bone marrow aspiration and biopsy, and blood and saliva sample collection throughout the study,

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

In a real-world study of 152 patients with relapsed and/or refractory multiple myeloma treated with carfilzomib plus dexamethasone, the overall response rate was 71.1%, indicating that this treatment is effective in a clinical setting.

Patients classified as trial-unfit had significantly shorter progression-free survival (3.6 months) and overall survival (15.0 months) compared to trial-fit patients (7.3 months and 36.8 months, respectively), highlighting the importance of patient fitness in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment outcomes of carfilzomib plus dexamethasone in patients with relapsed and/or refractory multiple myeloma, focusing on the impact of trial-fitness: CAtholic REsearch network for Multiple Myeloma study (CAREMM-2203). Park, SS., Goo, SY., Jeon, YW., et al.[2023]

In a phase 2 study involving 72 patients with newly diagnosed multiple myeloma, the combination of carfilzomib and dexamethasone (Kd) achieved a remarkable overall response rate of 90%, with 7% of patients reaching a complete response and 58% achieving a very good partial response.

The treatment was generally well-tolerated, with most adverse events being low grade; however, there was an 11.1% incidence of grade 3 or higher cardiovascular events, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. Forsberg, PA., Rossi, AC., Boyer, A., et al.[2020]

In a phase II trial involving 300 patients, carfilzomib combined with cyclophosphamide and dexamethasone (KCd) showed a higher overall response rate (84.0%) compared to bortezomib with the same regimen (VCd, 68.1%), indicating that KCd is at least as effective as VCd for treating myeloma.

Carfilzomib maintenance therapy significantly improved progression-free survival, with a median of 11.9 months compared to 5.6 months for those not receiving maintenance, highlighting its efficacy in prolonging treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib or bortezomib in combination with cyclophosphamide and dexamethasone followed by carfilzomib maintenance for patients with multiple myeloma after one prior therapy: results from a multicenter, phase II, randomized, controlled trial (MUKfive). Yong, KL., Hinsley, S., Auner, HW., et al.[2021]

In a study of 315 patients with relapsed and refractory multiple myeloma, carfilzomib monotherapy showed a similar overall survival (OS) rate compared to a control regimen of low-dose corticosteroids and optional cyclophosphamide, with median OS of 10.2 months for carfilzomib versus 10.0 months for control.

Carfilzomib demonstrated a higher overall response rate (19.1%) compared to the control group (11.4%), although both groups experienced similar progression-free survival and comparable rates of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Hájek, R., Masszi, T., Petrucci, MT., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06627751

Study Details | NCT06627751 | Mezigdomide, Carfilzomib ... This phase II trial studies how well mezigdomide/carfilzomib/dexamethasone (MeziKD) works in treating patients with multiple myeloma (MM) that has come back ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1025/531470/Mezigdomide-MEZI-Plus-Dexamethasone-DEX-and

Mezigdomide (MEZI) Plus Dexamethasone (DEX) and ... Conclusions: With longer follow-up, MeziVd and MeziKd in RRMM confirmed promising efficacy and a manageable safety profile at all dose levels ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303194

Mezigdomide plus Dexamethasone in Relapsed and ... The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07928

Mezigdomide, Carfilzomib, and Dexamethasone for the ... This phase II trial studies how well mezigdomide/carfilzomib/dexamethasone (MeziKD) works in treating patients with multiple myeloma (MM) that has come back ...

5. multiplemyelomahub.com multiplemyelomahub.com/medical-information/celmods-for-the-treatment-of-mm-latest-clinical-trial-data

CELMoDs for the treatment of MM: Latest clinical trial data The 1.0 mg dose of mezigdomide achieved the highest ORR at 60%, as well as the highest rate of very good partial response at 20% (Figure 5). The ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024016975

MM-520 Mezigdomide (MEZI) Plus Dexamethasone (DEX) ... Excluding all infections, grade 3–4 non-hematologic TEAEs were low. Overall response rate was 75.0% (MeziVd), 84.2% (MeziVd-1.0 mg), and 85.2% (MeziKd). In the ...

7. cancernetwork.com cancernetwork.com/view/mezigdomide-regimens-show-promise-in-pretreated-r-r-multiple-myeloma

Mezigdomide Regimens Show Promise in Pretreated R/R ... Mezigdomide with dexamethasone and bortezomib or carfilzomib led to a median PFS exceeding 1 year across 3 cohorts in those with relapsed/refractory MM.