Mezigdomide, Carfilzomib, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma in Patients With Extramedullary Disease

NCT06627751 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: I-3576824
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Refractory Multiple Myeloma; Extramedullary Disease in Multiple Myeloma; Recurrent Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate

  Will be assessed in patients with serologically measurable disease. Will be defined as the percentage of patients with an objective response of partial response (PWR) or better by International Myeloma Working Group criteria on 2 consecutive evaluations among the eligible patients who began protocol treatment. Will be evaluated using a one-sided Binomial test and a 90% credible region for the overall response rate will be constructed using Jeffrey's prior method

  At the end of cycle 6 (each cycle is 28 days).

• Clinical benefit rate

  Will be assessed in patients with non- or oligo-secretory disease. Clinical benefit rate is the percentage of patients who remain progression-free and on protocol treatment for at least 6 months among the eligible patients who began protocol treatment. A 90% binomial credible region will be constructed for the clinical benefit rate using Jeffrey's prior method.

  At the end of cycle 6 (each cycle is 28 days)

Secondary Outcomes (5)

• Incidence of Adverse Events (AEs)

  Up to 30 days after last dose of study drug

• Duration of response

  From the first documentation of response (≥ PR) to the first documentation of progressive disease or death, assessed up to 3 years

• Progression Free survival

  Time from first dose of mezigdomide to disease progression or death from any cause, whichever occurs first, assessed up to 3 years

• Overall Survival

  Time from first dose of mezigdomide to death from any cause, assessed up to 3 years

• Imaging Response

  At screening, after 3 cycles of treatment (or progression, whichever occurs first), after 6 cycles of treatment, and then every 6 months for 3 years or until progression, start of a new therapy, or death (whichever occurs first)

Study Arms (1)

Treatment - MeziKD

EXPERIMENTAL

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,

Biological: Mezigdomide; Drug: Carfilzomib; Drug: Dexamethasone; Procedure: Echocardiography; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Computed Tomography Assisted Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Biospecimen Collection

Interventions

Mezigdomide BIOLOGICAL

Given PO

Also known as: BMS 986348, CC-92480

Treatment - MeziKD

Carfilzomib DRUG

Given IV

Also known as: CFZ

Treatment - MeziKD

Dexamethasone DRUG

Given PO

Also known as: Adexone, Baycadron, Cortidexason, Decadron, Dekacort, Fortecortin, Gammacorten, Hexadecadrol, Loverine, Millicorten, Orgadrone, Spersadex, TaperDex, Visumetazone

Treatment - MeziKD

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment - MeziKD

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: PET, PET scan

Treatment - MeziKD

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan

Treatment - MeziKD

Computed Tomography Assisted Biopsy PROCEDURE

Undergo CT guided tumor Biopsy

Also known as: CT Assisted Biopsy

Treatment - MeziKD

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration biopsy

Treatment - MeziKD

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Treatment - MeziKD

Biospecimen Collection PROCEDURE

Undergo blood and saliva sample collection

Also known as: Biological Sample Collection

Treatment - MeziKD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years of age
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• RRMM patients with one or more prior lines of therapy with at least one ES or PS lesion that is accessible to a biopsy. Accessibility will be assessed by the MM tumor board
• Measurable disease meeting at least one of the following:
• Serum M-protein ≥1 g/dL
• Urine M-protein ≥200 mg/24 h
• Serum FLC assay: involved FLC level ≥10 mg/dL provided serum FLC ratio is abnormal
• Up to 10 patients without measurable disease can be enrolled but screening imaging and/or bone marrow biopsy have to confirm RRMM. Follow-up response assessment will be performed with imaging using RECIST 1.1 and Deauville Criteria and bone marrow biopsies
• Absolute neutrophil count: ≥ 1 x 10\^9/L
• Platelets: ≥ 75 x 10\^9/L
• Total bilirubin: ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]): ≤ 3 x ULN
• Renal function: Estimated creatinine clearance ≥ 30 mL/min (Cockroft-Gault)
• Adequate cardiac pump function with a left ventricular ejection fraction of ≥ 40%
• Women of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for at least 28 days after the last dose of mezigdomide or 6 months after the last dose of carfilzomib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Participant has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide (including ≥ grade 3 rash during prior thalidomide, lenalidomide, or pomalidomide therapy), carfilzomib or dexamethasone, any cereblon E3 ligase modulators (CELMoD) agents, or the excipients contained in the formulations, or participant has any contraindications per local prescribing information
• Administration of strong CYP3A modulators or proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) within 2 weeks of starting study intervention
• Participant is unable or unwilling to undergo protocol required thromboembolism prophylaxis
• Patient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
• Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participation in this study
• Known active infection requiring parenteral or oral anti-infective treatment within the past 14 days
• Participant has a history of prior malignancy other than MM, except if the participant has been free of disease for ≥ 3 years or the participant had 1 of the following noninvasive malignancies treated with curative intent without known recurrence:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Stage 1 bladder cancer
• Incidental histological findings of localized prostate cancer such as tumor stage 1a or 1b (T1a or T1b) using the tumor, nodes, and metastasis (TNM) classification of malignant tumors OR prostate cancer that has been treated with curative intent
• Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to patient registration
• Pregnant or breast-feeding females
• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
• Known active HIV or hepatitis B or C viral infection

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate; dexamethasone acetate; dexamethasone 21-phosphate; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Jens Hillengass, MD

  Roswell Park Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ASK RPCI

CONTACT

8772757724; askroswell@roswellpark.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2024
• First Posted: October 4, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2030
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)