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

Primary Purpose

Smoldering Plasma Cell Myeloma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dexamethasone
Iberdomide Hydrochloride
Quality-of-Life Assessment
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Smoldering Plasma Cell Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Emory University Hospital/Winship Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A (iberdomide hydrochloride, dexamethasone)

Arm B (iberdomide hydrochloride)

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Progression-free survival
Will be estimated with the Kaplan-Meier method with 95% confidence interval (CI) for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Time to progression
Will be estimated with the Kaplan-Meier method with 95% CI for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Overall survival
Will be estimated with the Kaplan-Meier method with 95% CI for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Rate of grade 3-4 adverse events
Adverse event data will be described and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events guidelines. Grade 3-4 adverse events will be estimated as frequency and percentage, and then compared between the two patient groups using Chi-Square test.
Successful stem cell mobilization
Defined as collection of 3.5 x 10^6 CD34 cells per kilogram weight.

Full Information

First Posted
February 11, 2021
Last Updated
June 9, 2023
Sponsor
Emory University
Collaborators
Bristol-Myers Squibb, National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04776395
Brief Title
Iberdomide Alone or in Combination With Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma
Official Title
Iberdomide in Intermediate- and High-Risk Smoldering Myeloma (SMM) Patients: A Phase 2 Study With a Safety Run-in
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2021 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
August 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
Bristol-Myers Squibb, National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) of iberdomide hydrochloride (iberdomide) and iberdomide with dexamethasone in intermediate- and high-risk smoldering multiple myeloma (SMM). SECONDARY OBJECTIVES: I. To determine the 1- and 2- year progression free survival rates of patients receiving iberdomide with and without dexamethasone in intermediate-risk and high-risk smoldering myeloma. II. To determine the time to progression, and overall survival of patients with intermediate- and high-risk smoldering myeloma receiving iberdomide with and without dexamethasone. III. To study the risk of adverse hematologic and non-hematologic events observed in patients receiving iberdomide with and without dexamethasone for treatment of intermediate- and high-risk smoldering myeloma. IV. To evaluate stem cell mobilization failure and early stem cell mobilization feasibility. TERTIARY/EXPLORATORY OBJECTIVES: I. To assess the effects of iberdomide on cereblon targets Aiolos and Ikaros in natural killer (NK)- and T- cells. II. To measure the effect of iberdomide with and without dexamethasone on T-cell and NK-cell counts and activation. III. To determine the prognostic impact of high-risk cytogenetic abnormalities on clinical outcomes. IV. To assess minimal residual disease (MRD) on bone marrow samples in subjects who achieved a complete response (CR) or better and evaluate the correlation between MRD status and clinical outcome measures. V. To assess the association between anti-tumor activity and immune cells in tumor and blood. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive iberdomide hydrochloride orally (PO) once daily (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. ARM B: Patients receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks and then every 6 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smoldering Plasma Cell Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (iberdomide hydrochloride, dexamethasone)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B (iberdomide hydrochloride)
Arm Type
Active Comparator
Arm Description
Patients receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
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
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Iberdomide Hydrochloride
Other Intervention Name(s)
CC-220 Hydrochloride
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Overall response rate
Description
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).
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Will be estimated with the Kaplan-Meier method with 95% confidence interval (CI) for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Time Frame
From start of protocol therapy to disease progression or death from any cause, whichever comes first, assessed at 1 and 2 years
Title
Time to progression
Description
Will be estimated with the Kaplan-Meier method with 95% CI for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Time Frame
From start of protocol therapy to disease progression, assessed at 1 and 2 years
Title
Overall survival
Description
Will be estimated with the Kaplan-Meier method with 95% CI for the two randomized arms separately and combined. Cox proportional hazards models will be further used to compare the two randomized arm with hazard ratio and its 95% CI reported.
Time Frame
From start of protocol therapy to death, censoring patients who are alive at last follow-up, assessed at 1 and 2 years
Title
Rate of grade 3-4 adverse events
Description
Adverse event data will be described and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events guidelines. Grade 3-4 adverse events will be estimated as frequency and percentage, and then compared between the two patient groups using Chi-Square test.
Time Frame
Up to 30 days after the last day of study participation
Title
Successful stem cell mobilization
Description
Defined as collection of 3.5 x 10^6 CD34 cells per kilogram weight.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nisha S. Joseph, MD
Phone
404-778-1900
Email
nisha.sara.joseph@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nisha S Joseph, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bryan Burton
Phone
404-778-1780
Email
bryan.james.burton@emory.edu
First Name & Middle Initial & Last Name & Degree
Nisha S. Joseph, MD

12. IPD Sharing Statement

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

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