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

NCT04776395 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00001731NCI-2020-08351WINSHIP5157-20P30CA138292
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Assessed per International Myeloma Working Group response criteria (to be done with serum and urine immunologic studies monthly; bone marrow biopsy and repeat imaging at either complete response or progressive disease).

  Up to 3 years

Secondary Outcomes (5)

• Progression-free survival

  From start of protocol therapy to disease progression or death from any cause, whichever comes first, assessed at 1 and 2 years

• Time to progression

  From start of protocol therapy to disease progression, assessed at 1 and 2 years

• Overall survival

  From start of protocol therapy to death, censoring patients who are alive at last follow-up, assessed at 1 and 2 years

• Rate of grade 3-4 adverse events

  Up to 30 days after the last day of study participation

• Successful stem cell mobilization

  Up to 3 years

Study Arms (2)

Arm A (iberdomide hydrochloride, dexamethasone)

EXPERIMENTAL

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.

Drug: Dexamethasone; Drug: Iberdomide Hydrochloride; Other: Quality-of-Life Assessment

Arm B (iberdomide hydrochloride)

ACTIVE COMPARATOR

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

Drug: Dexamethasone; Drug: Iberdomide Hydrochloride; Other: Quality-of-Life Assessment

Interventions

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, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm A (iberdomide hydrochloride, dexamethasone); Arm B (iberdomide hydrochloride)

Iberdomide Hydrochloride DRUG

Given PO

Also known as: CC-220 Hydrochloride

Arm A (iberdomide hydrochloride, dexamethasone); Arm B (iberdomide hydrochloride)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (iberdomide hydrochloride, dexamethasone); Arm B (iberdomide hydrochloride)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Emory University: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; iberdomide

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nisha S Joseph, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nisha S. Joseph, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: March 1, 2021
• Study Start: July 9, 2021
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-03

Locations

US (1)