Clinical Trials /

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

NCT04776395

Description:

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.

Related Conditions:
  • Smoldering Plasma Cell Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: STUDY00001731
  • SECONDARY ID: NCI-2020-08351
  • SECONDARY ID: WINSHIP5157-20
  • SECONDARY ID: P30CA138292
  • NCT ID: NCT04776395

Conditions

  • Smoldering Plasma Cell Myeloma

Interventions

DrugSynonymsArms
DexamethasoneAacidexam, 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, ZoDexArm A (iberdomide hydrochloride, dexamethasone)
Iberdomide HydrochlorideCC-220 HydrochlorideArm A (iberdomide hydrochloride, dexamethasone)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (iberdomide hydrochloride, dexamethasone)ExperimentalPatients 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.
  • Dexamethasone
  • Iberdomide Hydrochloride
Arm B (iberdomide hydrochloride)Active ComparatorPatients receive iberdomide hydrochloride PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Dexamethasone
  • Iberdomide Hydrochloride

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% or sheets of plasma cells

               -  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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 3 years
Safety Issue:
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).

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:From start of protocol therapy to disease progression or death from any cause, whichever comes first, assessed at 1 and 2 years
Safety Issue:
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.
Measure:Time to progression
Time Frame:From start of protocol therapy to disease progression, assessed at 1 and 2 years
Safety Issue:
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.
Measure:Overall survival
Time Frame:From start of protocol therapy to death, censoring patients who are alive at last follow-up, assessed at 1 and 2 years
Safety Issue:
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.
Measure:Rate of grade 3-4 adverse events
Time Frame:Up to 30 days after the last day of study participation
Safety Issue:
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.
Measure:Successful stem cell mobilization
Time Frame:Up to 3 years
Safety Issue:
Description:Defined as collection of 3.5 x 10^6 CD34 cells per kilogram weight.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Emory University

Last Updated

April 12, 2021