Combining Elotuzumab and Iberdomide with Dexamethasone for Relapsed Multiple Myeloma

Inclusion Criteria:

* Previously diagnosed with MM based on standard IMWG criteria
* Patient has given voluntary written informed consent before any study-related procedures not part of normal medical care are performed, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* Patient who has been treated with at least 4 prior lines of anti-myeloma treatment including immunomodulating agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
* In addition, to at least 4 prior lines of anti-myeloma treatment, patient has received ide-cel in accordance with the FDA approved US Prescribing Information and has achieved at least a partial response, and is within 90 days of infusion
* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
* Screening Laboratory evaluations within the following parameters

  * Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors cannot be used more recently than 7 days prior to initiation of therapy)
  * Platelet count ≥ 75,000 cells/dL (75 x 109/L) (without transfusions during the 7 days prior to initiation of therapy)
  * Hemoglobin ≥ 8.0 g/dL (RBC transfusions are permitted)
  * Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
  * AST or ALT ≤ 3x ULN
  * Creatinine clearance ≥ 30 ml/min according to the Cockroft-Gault formula:

    * Female CrCl = \[(140 - age in years) x weight in kg x 0.85\] / \[72 x serum creatinine in mg/dL\]
    * Male CrCl = \[(140 - age in years) x weight in kg x 1.00\] / \[72 x serum creatinine in mg/dL\]
* Age ≥18 years.
* Ability to understand and the willingness to sign a written informed consent document.
* A Female of childbearing potential (FCBP) must:

  * Have two negative pregnancy tests before enrollment and randomization into the clinical studies and prior to each re-supply of study drug during the clinical studies based on the frequency outlined in the Pregnancy Prevention Plan (PPP, Appendix D).
  * Sexually active FCBP must agree to use protocol-specified contraceptive methods during participation in the clinical studies and for at least 28 days after the last dose of study drug.
* Sexually active males (including those who have had a vasectomy) must agree to use protocol specified contraceptive methods during participation in the clinical studies and for at least 28 days after the last dose of study drug.
* All participants (male and female with or without childbearing potential) must agree to abstain from donating blood products for at least 28 days after the last dose of study drug and semen or sperm while taking study drug and for at least 28 days after the last dose of study drug.

Exclusion Criteria

* Prior exposure to Iberdomide
* Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
* Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy
* Known central nervous system involvement.
* Systemic treatment, within 14 days before the first dose of treatment, with strong CYP3A or inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort OR systemic treatment within 14 days of the first dose of treatment with a strong inhibitor of CYP1A2 (ciprofloxacin, fluvoxamine, cimetidine, enoxacin, ethynyl estradiol, mexiletine)
* Any medical or psychiatric illness/social situation that in the Investigator's opinion, would impose excessive risk to the patient, would adversely affect his/her participating in this study or would limit compliance with study requirements.
* Currently active graft versus host disease of any stage or grade after allogeneic stem cell transplantation
* Prior major surgical procedure or radiation therapy within 14 days of initiation of therapy.

  * Those who require a limited course of radiation for management of bone pain more than 14 days out from initiation of therapy are not excluded
* Any active, or uncontrolled cardiovascular conditions, including but not limited to uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, grade 3 thromboembolic event or myocardial infarction within the past 6 months.
* The following therapies within the stated time frames prior to initiation of therapy:

  * Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 21 days (42 days for nitrosoureas).
  * The use of live vaccines within 30 days.
  * IMiDs or proteasome inhibitors within 14 days.
  * Other investigational therapies and/or monoclonal antibodies within 4 weeks.
  * Prior peripheral stem cell transplant within 12 weeks.
  * Prior allogeneic stem cell transplantation with active graft-versus-host-disease.
* Those who require a limited course of daily requirement for corticosteroids (equivalent to \>10 mg/day prednisone, though \>10mg/day is acceptable if physiological levels require, so long as the dose is stable for at least 7 days prior to initiation of therapy. Inhalation corticosteroids are exempt from this criterion.

  * Lower amounts of corticosteroids that are not part of a daily requirement within 14 days prior to initiating therapy
* Concurrent symptomatic amyloidosis or plasma cell leukemia
* POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
* Infection requiring systemic antibiotic therapy or other serious infection within 7 days of starting therapy.

  * Those who are on prophylactic antibiotics only, or on antibiotics and have confirmation of resolution of active infection are eligible.
* Known seropositive for active viral infection with human immunodeficiency virus (HIV) hepatitis B (HBV) or hepatitis C viral (HCV). Those who are seropositive because of hepatitis B vaccine are eligible. Patients who are positive for HBV core antibody or HBV surface antigen must have a negative polymerase chain reaction (PCR) result prior to enrollment. Those who are PCR positive will be excluded
* Female patients who are pregnant or lactating.
* Participants who are receiving any other investigational agents for any indication
* History of erythema multiforme or severe hypersensitivity to prior IMiD's® or those who have a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
* Inability to tolerate thromboprophylaxis
* Failure to have fully recovered (≤ Grade 2 according to CTCAE v 5) from the reversible effects of prior chemotherapy