Elotuzumab, CC-92480, and Dexamethasone for the Treatment of Relapsed or Refractory Myeloma After CD38- and BCMA-Targeted Therapies

NCT05981209 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-22207NCI-2023-05518
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the safety, side effects, and best dose of CC-92480 in combination with elotuzumab and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment or has not responded to previous treatment (refractory). Multiple myeloma (MM) remains the second most common hematologic malignancy in the United States. A number of therapies have been approved for patients with MM, including CD38- and B-cell maturating antigen (BCMA)-targeted therapies (antibody and plasma cell treatments that help the body's immune system to kill cancer cells); however, patients will often relapse and become refractory to these therapies. Because of this, it is important to identify effective treatment options for patients progressing on anti-CD38 therapy and BCMA-directed therapies. Elotuzumab is a humanized IgG1 monoclonal antibody, which is a type of protein that can bind to other target cells to prevent them from working the way they should or cause them to act differently. Elotuzumab works by targeting a protein called SLAMF7, which is present on myeloma cells, and makes it easier for the immune system to target the cancer. CC-92480 works by binding to a protein called CRBN that triggers the breakdown of proteins: Ikaros and Aiolos, leading to cell death in multiple myeloma cells. Dexamethasone is a synthetic adrenocortical steroid, or steroid normally naturally made by the adrenal gland in the brain which has been produced in a laboratory, that helps to regulate the amount of different chemicals and water that are being processed by the kidneys. It is also used in patients with myeloma to help treat their disease. The combination of CC-92480 with elotuzumab and dexamethasone may be a safe and effective treatment when given to patients with relapsed or recurrent MM.

Conditions

Refractory Multiple Myeloma; Recurrent Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• The recommended phase 2 dose of mezigdomide (CC-92480) in combination with elotuzumab and dexamethasone

  The dose limiting toxicity (DLT) will be defined as one or more of the following toxicities considered to be at least possibly related to the study drug, occurring during cycle 1 of therapy. Furthermore, inability to take \>= 75% of the planned CC-92480 doses, or receive cycle 2 day 1 doses due to a drug-related adverse event occurring in cycle 1 will be considered a DLT.

  Up to 28 days (Cycle 1)

• Incidence of adverse events

  Adverse events and toxicities of the combination regimen will be summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicities will be assessed overall, as well as by dose level. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of severe (grade 3+) adverse events or toxicities will be described. Will also assess tolerability of the regimen through assessing the number of patients who required dose modifications and/or dose delays. In addition, will capture the proportion of patients who go off treatment due to adverse reactions. All patients who have received at least one dose of any of the study regimen will be evaluable for toxicity.

  Up to 2 years

Secondary Outcomes (12)

• Time to progression (TTP)

  From start of treatment until objective tumor progression; with death as a competing risk, assessed at 1 year

• Time to response (TTR)

  From start of treatment until measurement criteria are first met for PR, very good partial response (VGPR), or complete response (CR) (whichever status is recorded first), assessed at 1 year

• Duration of response (DOR)

  From the time measurement criteria are first met for partial response or better (whichever status is recorded first) until the first date of progressive disease or death, assessed at 1 year

• Very good partial response (VGPR) or better rates

  From start of treatment until disease progression or death, assessed at 1 year

• Complete Response (CR)

  From start of treatment until disease progression or death, assessed at 1 year

Study Arms (1)

Treatment (elotuzumab, CC-92480, dexamethasone)

EXPERIMENTAL

Patients receive elotuzumab IV on days 1, 8, 15, and 22 of cycles 1 and 2 and then on day 1 of each subsequent cycle. Patients also receive CC-92480 PO on days 1-21 of each cycle and dexamethasone IV or PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo an ECHO during screening and undergo MRI, CT, or x-ray imaging during screening and on study as clinically indicated. Patients also undergo blood sample collection as well as bone marrow biopsy and aspiration during screening and on study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Echocardiography; Biological: Elotuzumab; Procedure: Magnetic Resonance Imaging; Biological: Mezigdomide; Procedure: X-Ray Imaging

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (elotuzumab, CC-92480, dexamethasone)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (elotuzumab, CC-92480, dexamethasone)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (elotuzumab, CC-92480, dexamethasone)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (elotuzumab, CC-92480, dexamethasone)

Dexamethasone DRUG

Given IV or PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (elotuzumab, CC-92480, dexamethasone)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (elotuzumab, CC-92480, dexamethasone)

Elotuzumab BIOLOGICAL

Given IV

Also known as: BMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063

Treatment (elotuzumab, CC-92480, dexamethasone)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (elotuzumab, CC-92480, dexamethasone)

Mezigdomide BIOLOGICAL

Given PO

Also known as: BMS 986348, BMS-986348, BMS986348, CC 92480, CC-92480, CELMoD CC-92480, Cereblon E3 Ligase Modulation Drug CC-92480, Cereblon E3 Ubiquitin Ligase Modulating Agent CC-92480, Cereblon Modulator CC-92480

Treatment (elotuzumab, CC-92480, dexamethasone)

X-Ray Imaging PROCEDURE

Undergo x-ray imaging

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Treatment (elotuzumab, CC-92480, dexamethasone)

Eligibility Criteria

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

You may qualify if:

• Patients 18 years of age or older with evidence of relapsed or refractory disease as defined by International Myeloma Working Group (IMWG) criteria and measurable disease as defined by any of the following:
• Serum M-protein \>= 1.0 g/dl
• Urine monoclonal protein \>= 200 mg/24h
• Involved free light chain (FLC) level \>= 10mg/dl (\>= 100mg/l) and an abnormal serum free light chain ratio (\< 0.26, or \> 1.65)
• Patients must have had at least 2 prior lines of therapy including lenalidomide, proteasome inhibitor (PI), anti-CD38 directed antibody, and BCMA-targeted therapy
• Prior elotuzumab is permitted but patients with progressive disease (PD) as best reponse on elotuzumab are excluded; at least 6 months must have lapsed from prior elotuzumab exposure
• Patients must have hemoglobin \>= 7g/dL
• Absolute neutrophil count (ANC) \>= 1000/uL
• Platelets \>= 70,000/uL
• If plasma cell percentage on bone marrow biopsy aspirate or core is \> 30%, platelet requirement will be adjusted to 50,000/ul
• Total bilirubin =\< 1.5 x the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase \< 2.5 x the ULN
• Calculated creatinine clearance of \>= 45ml/min using Modification of Diet in Renal Disease (MDRD) formula
• Left ventricular ejection fraction \>= 30%; baseline echocardiography (ECHO) is not required if ECHO was done within the preceding one year and patients do not have new signs/symptoms suggestive of heart failure
• No uncontrolled arrhythmias

You may not qualify if:

• Patients with Waldenstrom macroglobulinemia, primary amyloid light chain (AL) amyloidosis, primary plasma cell leukemia, or polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome
• Patients with secondary plasma cell leukemia are permitted
• Patients with peripheral neuropathy \> National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2, or grade 2 peripheral neuropathy with pain
• Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
• Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
• Patients with history of anaphylaxis or hypersensitivity to elotuzumab, lenalidomide, or pomalidomide
• Concurrent use of strong CYP3A modulators ≤ 2weeks; concurrent use of proton-pump inhibitors =\< 1 weeks prior to started CC-92480; potassium competitive acid blockers ≤ 2days prior to starting CC-92480
• Unacceptable respiratory risk factors defined by any one of the following criteria:
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than 50% of predicted normal
• Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
• Unacceptable cardiac risk factors defined by any of the following criteria:
• Left ventricular ejection fraction \< 30%
• Complete left bundle branch, bifascicular block or clinically significant abnormal electrocardiogram (EKG) finding at screening
• A prolongation of QT interval on screening ECG as defined by repeated demonstration of a QTc interval \> 470 msec using Fridericia's QT correction formula; a family history of long QT syndrome
• Myocardial infarction within 6 months

Sponsors & Collaborators

• Abdullah Khan: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Specimen Handling; Biopsy; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; elotuzumab; Magnetic Resonance Spectroscopy; X-Rays; Phantoms, Imaging

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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; 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; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Abdullah M Khan, MBBS, MSc

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 8, 2023
• Study Start: December 21, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)