Recruiting
Phase 2

Mezigdomide, Carfilzomib, Dexamethasone

Sponsor:

Roswell Park Cancer Institute

Code:

NCT06627751

Conditions

Extramedullary Disease in Multiple Myeloma

Recurrent Multiple Myeloma

Refractory Multiple Myeloma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Mezigdomide

Carfilzomib

Dexamethasone

Echocardiography

Positron Emission Tomography

Study Details

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

Extramedullary Disease in Multiple Myeloma

Recurrent Multiple Myeloma

Refractory Multiple Myeloma

Study ID

NCT06627751

Start date

May 1, 2025

Status verified date

Aug, 2026

Completion date

May 1, 2030

Anticipated

Primary completion date

May 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • Male patients (non-vasectomized) must agree to use contraception during the treatment period and for at least 28 days after the last dose of mezigdomide or 3 months after the last dose of carfilzomib and refrain from donating sperm during this period
  • Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • 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
  • Known history of HIV infection
  • Systemic amyloidosis or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[M-protein\] and skin changes)
  • Prior peripheral stem cell transplant within 12 weeks of study enrollment
  • Radiotherapy within 14 days prior to cycle 1 day 1. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
  • Known intolerance to steroid therapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, severe cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Carfilzomib-refractory in the most recent line of therapy
  • Prior treatment with mezigdomide
  • Contraindication against conscious sedation
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Study Design

Enrollment

28 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment - MeziKD

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,

Interventions

Mezigdomide

Given PO

Carfilzomib

Given IV

Dexamethasone

Given PO

Echocardiography

Undergo ECHO

Positron Emission Tomography

Undergo PET/CT

Computed Tomography

Undergo PET/CT

Computed Tomography Assisted Biopsy

Undergo CT guided tumor Biopsy

Bone Marrow Aspiration

Undergo bone marrow aspiration biopsy

Bone Marrow Biopsy

Undergo bone marrow biopsy

Biospecimen Collection

Undergo blood and saliva sample collection

Primary outcome measure

  • Overall Response Rate [ Time Frame: At the end of cycle 6 (each cycle is 28 days). ]
  • Clinical benefit rate [ Time Frame: At the end of cycle 6 (each cycle is 28 days) ]

Central Contacts and Locations

Central contacts

ASK RPCI

8772757724askroswell@roswellpark.org

Locations

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

Contacts

Ask RPCI

800-767-9355ASKRPCI@roswellpark.org

Principal Investigator:

Jens Hillengass

More Information

Sponsor

Roswell Park Cancer Institute

Last update posted

Aug 18, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Roswell Park Cancer Institute on 2026-08-18.