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

Roswell Park Comprehensive Cancer Center

Status and phase

Enrolling

Phase 2

Conditions

Extramedullary Disease in Multiple Myeloma

Refractory Multiple Myeloma

Recurrent Multiple Myeloma

Treatments

Biological: Mezigdomide

Procedure: Biospecimen Collection

Procedure: Echocardiography

Procedure: Computed Tomography Assisted Biopsy

Procedure: Bone Marrow Aspiration

Procedure: Positron Emission Tomography

Drug: Carfilzomib

Procedure: Bone Marrow Biopsy

Procedure: Computed Tomography

Drug: Dexamethasone

Study type

Interventional

Funder types

Other

Identifiers

NCT06627751

I-3576824

Details and patient eligibility

About

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.

Enrollment

28 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

28 participants in 1 patient group

Treatment - MeziKD

Experimental group

Description:

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,

Treatment: