A Study of Iberdomide (CC-220) in Combination With Elotuzumab and Dexamethasone for Relapsed/Refractory Multiple Myeloma

NCT05560399 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: GCO 22-0016
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label study evaluating the safety, tolerability and efficacy of Iberdomide (CC-220) in combination with Elotuzumab and Dexamethasone in patients with RRMM. The researchers hypothesize that the combination of Iberdomide and Elotuzumab will synergize to promote myeloma cell death, resulting in an overall response rate of at least 53%, with an acceptable safety profile. Patients will be enrolled in a 3+3 dose escalation cohort to evaluate the safety of this combination and to establish the MTD (maximum tolerated dose). The MTD will be the dose for the patients enrolled in dose expansion cohort. A total maximum of 37 patients will be recruited: maximum 18 patients will be recruited in the dose escalation phase, followed by an additional 19 patients in the dose expansion cohort for a total of 25 patients treated at the MTD.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Iberdomide dose limiting toxicity

  The dose limiting toxicity (DLT) rate at the Maximum Tolerated Dose, defined as the proportion of patients in the safety population of the study that experience at least 1 DLT within the first cycle of Iberdomide (CC-220) in combination with Elotuzumab and Dexamethasone treated at the maximum tolerated dose (MTD).

  28 days

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  up to 3 months

• Number of adverse events (AE)

  up to 3 months

• Progression-free survival (PFS)

  up to 3 months

• Best Overall Response Rate (BOR)

  up to 3 months

• Duration of Response (DOR)

  up to 3 months

Study Arms (1)

Iberdomide, Elotuzumab and Dexamethasone

EXPERIMENTAL

Dose-Finding: Patients will be enrolled in a 3+3 dose escalation cohort. Dose-Expansion: additionally enrolled patients at the recommended maximum tolerated dose of Iberdomide as was determined in Part 1 (Dose-Finding Phase).

Drug: Iberdomide; Drug: Elotuzumab; Drug: Dexamethasone

Interventions

Iberdomide DRUG

Route of administration: oral pill. Schedule: Taken Once daily on days 1-21. Dose: will be tested at 1 mg, 1.3 mg, and 1.6mg. 1mg dose may be reduced to 0.75mg if not tolerated.

Also known as: CC-220

Iberdomide, Elotuzumab and Dexamethasone

Elotuzumab DRUG

Route of administration: IV Dose: 10 mg/kg for cycles 1 and 2. 20 mg/kg for cycle 3 and beyond. Schedule: Days 1, 8, 15, and 22 for cycles 1 and 2. Then taken on Day 1 (every 28 days) of each cycle thereafter.

Iberdomide, Elotuzumab and Dexamethasone

Dexamethasone DRUG

Route of administration: Oral pill or IV Dose: 36 mg within 24 hrs of day 1 of each cycle and day 8, 15, and 22 of cycle 1 and 2. 40 mg on days 8, 15, 22 of cycle 3 and all subsequent cycles. (20 mg for \> 75 years old). Schedule: On days that Elotuzumab is administered, Dexamethasone to be taken 28mg orally (for ≤75 years old) or 8mg orally (for \> 75 years old) between 3 and 24 hours before Elotuzumab plus 8 mg IV between 45 and 90 minutes before Elotuzumab for all patients. On days that Elotuzumab is not administered but a dose of Dexamethasone is scheduled (Days 8, 15, and 22 of cycle 3 and all subsequent cycles), 40 mg orally for ≤75 years older and 20 mg for

Iberdomide, Elotuzumab and Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• All subjects must have documented diagnosis of MM with disease progression per IMWG criteria during or after their last anti-myeloma therapy (Appendix D).
• All subjects must have measurable disease at screening, defined as one or more of the following:
• Serum IgG, IgA, IgM M-protein ≥ 0.5 g/dL
• Urinary M-Protein ≥ 200 mg urinary M-protein excretion in a 24-hour collection sample
• Involved serum free light chain (sFLC) ≥ 10 mg/dL provided the FLC ratio is abnormal.
• All patients must have ECOG Performance Status ≤ 2 (Appendix A).
• Subjects must have received at least 1 and at most 3 lines of therapy (note: induction and stem cell transplants with or without maintenance therapy is considered 1 line of therapy) including at least one IMiD (thalidomide, lenalidomide, pomalidomide), a proteosome inhibitor (bortezomib, carfilzomib, ixazomib), and an anti-CD38 agent (daratumumab, isatuximab).
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy tests (minimum sensitivity 25 IU/L or equivalent units of HCG), at 10-14 days prior to start of study drug; another within 24 hours prior to the start of study drug.
• Women must not be breastfeeding
• WOCBP must agree to follow instructions for method(s) of contraception for 1 month (4 weeks) before the start of treatment with study drugs, for the duration of treatment with study drugs, and for a total of 5 months post-treatment completion. This includes 2 methods of reliable birth control simultaneously:
• one highly effective form of contraception - tubal ligation, IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings, or implants), or partner's vasectomy, and;
• additional effective contraceptive method - male latex or synthetic condom, diaphragm, or cervical cap. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cells dyscrasia.
• Subjects with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), primary amyloidosis (no active multiple myeloma), Waldenström's macroglobulinemia, or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Subjects with active plasma cell leukemia (defined as either 20% of peripheral blood white blood cell count comprised of plasma/CD138+ cells or an absolute plasma cell count of 2 x 109/L)
• Subjects with Central Nervous System involvement with multiple myeloma
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
• Any serious concurrent medical conditions that may make the patient non-evaluable or put the patient's safety at risk
• Active infection that requires parenteral anti-infective treatment \>14 days
• Unable to tolerate thromboembolic prophylaxis while on the study
• Severe hypersensitivity reaction to prior IMiD (thalidomide, lenalidomide or pomalidomide)
• Grade \> 2 peripheral neuropathy (per NCI CTCAE v5.0)
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
• Known HIV infection or known acquired immunodeficiency syndrome (AIDS).
• Prior or concurrent malignancy, except for the following:
• Adequately treated basal cell or squamous cell skin cancer or in-situ carcinoma.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Multiple Myeloma Research Consortium: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Icahn School of Medicine

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

iberdomide; elotuzumab; Dexamethasone

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

Study Officials

• Samir Parekh, MBBS

  Icahn school of medicine

  PRINCIPAL INVESTIGATOR

• Cesar Rodriguez, MD

  Icahn School of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Part 1 is a dose-finding evaluation of Iberdomide in combination with Elotuzumab and Dexamethasone at their approved doses for patients with relapsed/refractory multiple myeloma. Part 2 of this study is an open-label, single-arm dose expansion cohort that will enroll additional patients at the recommended maximum tolerated dose of Iberdomide as determined in Part 1.

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: September 29, 2022
• Study Start: February 6, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)