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

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well mezigdomide/carfilzomib/dexamethasone (MeziKD) works in treating patients with multiple myeloma (MM) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) and have tumors from myeloma cells outside the bone marrow in the soft tissues or organs of the body (extramedullary disease \[EMD\]). Mezigdomide blocks important processes in myeloma cells and may lead to modulation of the immune system, including activation of T-lymphocytes, and downregulation of the activity of other proteins, some of which play key roles in the proliferation of certain cancer cell types. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is a type of corticosteroid and is used to kill myeloma cells. It is used with other drugs to treat multiple myeloma. Giving MeziKD may kill more cancer cells in patients with relapsed/refractory multiple myeloma (RRMM) with EMD.

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.

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

Research shows that the combination of Carfilzomib and Dexamethasone is effective in treating multiple myeloma, with a high overall response rate of 90% in newly diagnosed patients. Additionally, Carfilzomib has shown better response rates compared to similar drugs in other studies, indicating its potential effectiveness in combination therapies. ^{1 2 3 4 5}

How is the MeziKD drug for multiple myeloma different from other treatments?

The MeziKD drug combines carfilzomib, dexamethasone, and mezigdomide, which is unique because it includes mezigdomide, a novel component not typically used in standard multiple myeloma treatments. This combination may offer a new approach by potentially enhancing the effectiveness of existing therapies like carfilzomib and dexamethasone. ^{1 2 3 5 6}

Research Team

Jens Hillengass, MD

Principal Investigator

Roswell Park Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

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

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. [2020]

2. Germany 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). [2023]

3. Italy 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). [2021]

4. England 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). [2022]

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

Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma. [2019]

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

Carfilzomib-lenalidomide-dexamethasone vs lenalidomide-dexamethasone in relapsed multiple myeloma by previous treatment. [2022]