Recruiting

Phase 2

Iberdomide & DexamethasoneIberdomide Alone or in Combination With Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma

Sponsor:

Emory University

Code:

NCT04776395

Conditions

Smoldering Plasma Cell Myeloma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Dexamethasone

Iberdomide Hydrochloride

Quality-of-Life Assessment

Study Details

Brief summary:

This phase II trial studies the effects of iberdomide when given alone or in combination with dexamethasone in treating intermediate or high-risk smoldering multiple myeloma patients. Immunotherapy with iberdomide may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Dexamethasone is a synthetic steroid (similar to steroid hormones produced naturally in the adrenal gland), and is used with other drugs in the treatment of some types of cancer. Giving iberdomide with dexamethasone my improve time to progression to symptomatic myeloma with improved tolerability.

Conditions

Smoldering Plasma Cell Myeloma

Study ID

NCT04776395

Start date

Jul 9, 2021

Status verified date

May, 2026

Completion date

Sep 1, 2029

Anticipated

Primary completion date

Sep 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Subject must have intermediate- or high risk smoldering multiple myeloma (SMM) as confirmed by at least one of the following factors either at screening or within 28 days of screening:

Bone marrow clonal plasma cells >= 20% confirmed on either screening bone marrow biopsy or by outside pathology ≤5 years from initiation of study drug.
Abnormal serum free light chain ratio > 20 by serum free light chain (FLC) assay
Serum monoclonal protein >= 2 g/dL
Subject must have been diagnosed with SMM =< 5 years from initiation of study drug
Both men and women of all races and ethnic groups are eligible for this study
Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 60%) is required for eligibility
Absolute neutrophil count (ANC) >= 1500/uL
Hemoglobin (Hgb) > 11 g/dL
Platelet count >= 100,000 cells/mm\^3 and must be platelet and packed red blood cells (PRBC) transfusion independent with no granulocyte colony-stimulating factor (G-CSF) to ensure eligibility within 8 weeks of screening
Estimated creatinine clearance >= 30 mL/min as defined by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Cockcroft-Gault
Total bilirubin < 2 mg/dL except in subjects with congenital bilirubinemia such as Gilbert syndrome, in which case direct bilirubin =< 2 times the institutional upper limit of normal is required
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times the institutional upper limit of normal
Left ventricular ejection fraction >= 40%
Females of childbearing potential (FCBP) must have two negative pregnancy tests as verified by the investigator prior to starting study treatment. The effects of Iberdomide on the developing human fetus are unknown. For this reason, women of child-bearing potential 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. A FCBP must 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 (including dose interruptions), and for at least 28 days after the last dose of iberdomide. 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
Female of childbearing potential (FCBP) is a sexually mature woman who:

Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
The subject must be willing to comply with fertility requirements as below:

Male subjects must agree to use an adequate method of contraception for the duration of the study and for 3 months afterwards
Female subjects must be either postmenopausal, free from menses >= 2 years (yrs), surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from heterosexual activity starting with screening and for 3 months after last treatment in all patients
Patients must agree not to donate blood, sperm/ova while taking protocol therapy and for at least 4 weeks after stopping treatment
Subject must understand and voluntarily sign an informed consent form (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
Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Exclusion Criteria:

Multiple myeloma requiring treatment as defined by SLiM-CRAB criteria
Monoclonal gammopathy of undetermined significance (MGUS), polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome), plasma cell leukemia, primary systemic light chain (AL) amyloidosis, or Waldenstroms macroglobulinemia
Concurrent intravenous bisphosphonate use more often than once a year
Prior or ongoing treatment for plasma cell disorder
Active hepatitis B or C due to risk of infection made worse by study drug
If subject has human immunodeficiency virus (HIV), they must have a CD4 count >= 350, no history of acquired immune deficiency syndrome-related illness, and not currently prescribed zidovudine or stavudine
Subjects may be receiving concomitant low dose corticosteroids (e.g., prednisone up to but no more than 10 mg by mouth daily or its equivalent) for symptom management and comorbid conditions
Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV), unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements
Subjects with gastrointestinal disease that may significantly alter the absorption of iberdomide
Pregnant women are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to protocol treatment of the mother, breastfeeding should be discontinued
Current or prior use of immunosuppressive medication within 14 days prior to the first dose of iberdomide. The following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection); systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent steroids as premedication for hypersensitivity reactions (e.g, computed tomography \[CT\] scan pre-medications)

Study Design

Enrollment

68 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (iberdomide hydrochloride, dexamethasone)

Patients receive iberdomide hydrochloride PO QD on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

active comparator: Arm B (iberdomide hydrochloride)

Patients receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Dexamethasone

Given PO

Iberdomide Hydrochloride

Given PO

Quality-of-Life Assessment

Ancillary studies

Primary outcome measure

Overall response rate [ Time Frame: Up to 3 years ]

Central Contacts and Locations

Central contacts

Nisha S. Joseph, MD

404-778-1900 nisha.sara.joseph@emory.edu

Locations

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Bryan Burton

404-778-1780 bryan.james.burton@emory.edu

Principal Investigator:

Nisha S. Joseph, MD

More Information

Sponsor

Emory University

Last update posted

Jun 1, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Emory University on 2026-06-01.