Elotuzumab, Daratumumab, Iberdomide, and Dexamethasone for the Treatment of Relapsed Multiple Myeloma

NCT06785415 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MC230812NCI-2025-0013824-010000
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial tests the safety, side effects, and best dose of iberdomide and how well it works in combination with daratumumab, elotuzumab, and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed). Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Elotuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving iberdomide in combination with daratumumab, elotuzumab, and dexamethasone may be safe, tolerable and/or effective in patients with relapsed multiple myeloma.

Conditions

Recurrent Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (Phase 1)

  The maximum tolerated dose (MTD) of the combination of iberdomide, daratumumab, elotuzumab, and dexamethasone (IberDEd) will be defined as the highest tested dose level that is determined to have acceptable toxicity and tolerability based on dose limiting toxicity definitions.

  Up to 28 days

• Proportion of patients with very good partial response (VGPR) or better (Phase 2)

  Will be defined as a patient who has achieved a VGPR, complete response (CR), or stringent complete response (sCR) and maintained it on two consecutive evaluations at any time during therapy per International Myeloma Working Group (IMWG) criteria.

  Up to 3 years

Secondary Outcomes (6)

• Overall response rate (Phase 2)

  Up to 3 years

• Complete response rate (Phase 2)

  Up to 3 years

• Progression-free survival (Phase 2)

  Up to 3 years

• Overall survival (Phase 2)

  Up to 3 years

• Time to response (Phase 2)

  Up to 3 years

Study Arms (1)

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

EXPERIMENTAL

Patients receive iberdomide PO QD on days 1-21 of each cycle, daratumumab SC on days 1, 8, 15, 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive elotuzumab IV on days 1, 8, 15, and 22 of cycles 1 and 2, and on day 1 of subsequent cycles and dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12 or at the discretion of the treating physician. Cycles repeat every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy during screening, on study and optionally at disease progression and CT, bone scan, MRI or PET/CT during screening, on study or at the discretion of the treating physician and EOT. Patients may undergo chest x-ray during screening.

Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Procedure: Chest Radiography; Procedure: Computed Tomography; Biological: Daratumumab; Drug: Dexamethasone; Biological: Elotuzumab; Drug: Iberdomide; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

Interventions

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

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

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Chest Radiography PROCEDURE

Undergo chest x-ray

Also known as: Chest X-ray

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Computed Tomography PROCEDURE

Undergo CT and/or PET/CT

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

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Daratumumab BIOLOGICAL

Given SC

Also known as: Daratumumab Biosimilar HLX15, Daratumumab-fihj, Darzalex, HLX15, HuMax-CD38, JNJ 54767414, JNJ-54767414, JNJ54767414

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Dexamethasone DRUG

Given 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, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Elotuzumab BIOLOGICAL

Given IV

Also known as: BMS 901608, BMS-901608, BMS901608, Empliciti, HuLuc-63, HuLuc63, PDL 063, PDL-063, PDL063

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Iberdomide DRUG

Given PO

Also known as: CC 220, CC-220

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

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

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)

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 at the time of signing the informed consent form (ICF).
• Diagnosis of relapsed multiple myeloma with ≤ 3 prior lines of therapy including treatment with proteasome inhibitors (i.e., ixazomib, carfilzomib, bortezomib), immunomodulatory imide drugs (i.e., lenalidomide, pomalidomide), and anti-CD38 drugs (i.e., daratumumab, isatuximab). Patients are required to have received a proteasome inhibitor, immunomodulatory imide drug, or combination of the two drug classes during first-line treatment.
• Note: Prior treatment with iberdomide is not allowed. Patients should not be refractory simultaneously to all other drugs in the combination.
• Measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2.
• Hemoglobin ≥ 8.0 g/dL (obtained ≤14 days prior to registration).
• Absolute neutrophil count (ANC) ≥ 1000/m\^3 (obtained ≤14 days prior to registration).
• Platelet count ≥ 50,000/mm\^3. Note: It is not permissible to transfuse subjects to achieve minimum platelet counts (obtained ≤14 days prior to registration).
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3 x ULN for patients with Gilbert's syndrome) (obtained ≤14 days prior to registration).
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2 x ULN and alkaline phosphatase ≤ 1.5 x ULN (obtained ≤14 days prior to registration).
• Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault (obtained ≤14 days prior to registration).
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. Note: A person of childbearing potential (PCBP) is a person who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) and must:
• Have 2 negative pregnancy tests prior to starting study treatment and must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
• AND
• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment, and for at least 28 days after the last dose of iberdomide, 90 days after the last dose of daratumumab, 7 months after last dose of elotuzumab whichever is longer.

You may not qualify if:

• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant persons
• Nursing persons
• Men or women of childbearing potential who are unwilling to employ adequate contraception.
• Receiving any other concurrent chemotherapy, or any ancillary therapy considered investigational.
• Note: Bisphosphonates are supportive care rather than therapy and are thus allowed while on protocol treatment.
• Known to be human immunodeficiency virus (HIV) positive known or suspected active hepatitis C infection or seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]) at registration or ≤ 3 months prior to registration.
• Note: Participants with resolved hepatitis B infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded.
• EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Evidence of cardiovascular disease risk, as defined by any of the following:
• Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting ≤ three (3) months prior to registration.
• Class III or IV heart failure as defined by the New York Heart Association functional classification system \[NYHA, 1994\]
• Uncontrolled hypertension
• History of life-threatening ventricular arrhythmias.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Biopsy; X-Rays; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; elotuzumab; iberdomide; 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)

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

Study Officials

• Moritz Binder, MD, MPH

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.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

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: January 21, 2025
• Study Start: March 18, 2025
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2031
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

US (1)