Inclusion Criteria.
- - Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
- - Subject must understand and voluntarily sign an 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.
- - All subjects must have documented diagnosis of MM with disease progression per IMWG
criteria during or after their last anti-myeloma therapy (Appendix D).
- - All subjects must have measurable disease at screening, defined as one or more of the
following:
1.
Serum IgG, IgA, IgM M-protein ≥ 0.5 g/dL. 2. Urinary M-Protein ≥ 200 mg urinary M-protein excretion in a 24-hour collection
sample. 3. Involved serum free light chain (sFLC) ≥ 10 mg/dL provided the FLC ratio is
abnormal.
- - All patients must have ECOG Performance Status ≤ 2 (Appendix A).
- - Subjects must have received at least 1 and at most 3 lines of therapy (note: induction
and stem cell transplants with or without maintenance therapy is considered 1 line of
therapy) including at least one IMiD (thalidomide, lenalidomide, pomalidomide), a
proteosome inhibitor (bortezomib, carfilzomib, ixazomib), and an anti-CD38 agent
(daratumumab, isatuximab).
- - Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
tests (minimum sensitivity 25 IU/L or equivalent units of HCG), at 10-14 days prior to
start of study drug; another within 24 hours prior to the start of study drug.
- - Women must not be breastfeeding.
- - WOCBP must agree to follow instructions for method(s) of contraception for 1 month (4
weeks) before the start of treatment with study drugs, for the duration of treatment
with study drugs, and for a total of 5 months post-treatment completion.
This includes
2 methods of reliable birth control simultaneously:
1. one highly effective form of contraception
- - tubal ligation, IUD, hormonal (birth
control pills, injections, hormonal patches, vaginal rings, or implants), or
partner's vasectomy, and;
2.
additional effective contraceptive method
- - male latex or synthetic condom,
diaphragm, or cervical cap.
Reliable contraception is indicated even where there
has been a history of infertility, unless due to hysterectomy.
- - Males who are sexually active with WOCBP must always use a latex or synthetic condom
during any sexual contact with females of reproductive potential while taking
Iberdomide (CC-220) and for up to 90 days after discontinuing Iberdomide (CC-220),
even if they have undergone a successful vasectomy.
Male patients must not donate
sperm.
- - Azoospermic males and WOCBP who are continuously not heterosexually active are exempt
from contraceptive requirements.
However, they must still undergo pregnancy testing as
described in this section.
- - All subjects must agree not to share study medication.
- - Male subjects receiving Elotuzumab must agree to follow instructions for method(s) of
contraception for 1 month (4 weeks) before the start of treatment with study drugs,
for the duration of treatment with study drugs, and for a total of 7 months post
treatment completion.
- - Subjects must be willing to refrain from blood donations during study drug therapy and
for 90 days after therapy.
Exclusion Criteria. An individual who meets any of the following criteria will be excluded from participation
in this study:
- - Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of
plasma cells dyscrasia.
- - Subjects with monoclonal gammopathy of undetermined significance (MGUS), smoldering
multiple myeloma (SMM), primary amyloidosis (no active multiple myeloma),
Waldenström's macroglobulinemia, or POEMS syndrome (plasma cell dyscrasia with
polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Subjects with active plasma cell leukemia (defined as either 20% of peripheral blood
white blood cell count comprised of plasma/CD138+ cells or an absolute plasma cell
count of 2 x 109/L)
- Subjects with Central Nervous System involvement with multiple myeloma.
- - Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the patient from signing the informed consent form.
- - Any serious concurrent medical conditions that may make the patient non-evaluable or
put the patient's safety at risk.
- - Active infection that requires parenteral anti-infective treatment >14 days.
- - Unable to tolerate thromboembolic prophylaxis while on the study.
- - Severe hypersensitivity reaction to prior IMiD (thalidomide, lenalidomide or
pomalidomide)
- Grade > 2 peripheral neuropathy (per NCI CTCAE v5.0)
- Any positive test for hepatitis B virus or hepatitis C virus indicating acute or
chronic infection.
- - Known HIV infection or known acquired immunodeficiency syndrome (AIDS).
- - Prior or concurrent malignancy, except for the following:
1.
Adequately treated basal cell or squamous cell skin cancer or in-situ carcinoma.
2. Any other cancer from which the subject has been disease free for > 3 years prior
to study entry.
- - Prior treatment with Iberdomide (CC-220)
- Prior treatment with Elotuzumab.
- - Use of any anti-myeloma drug therapy within 14 days of the initiation of study drug
treatment or use of any experimental drug therapy within 28 days of the initiation of
study drug treatment.
- - Treatment with melphalan within 4 weeks of the first dose of study drug.
- - Treatment with corticosteroids (other than the Dexamethasone of anti-myeloma regimens)
within 3 weeks of the first dose of study drug, except for the equivalent of ≤ 10 mg
prednisone per day or corticosteroids with minimal to no systemic absorption (i.e.,
topical or inhaled corticosteroids)
- Prior autologous stem cell transplant within 12 weeks of the first dose of study drug.
- - Prior allogeneic stem cell transplant except subjects who have completed the stem cell
transplant > 12 months prior to first dose of study drug, have no history of graft
versus host disease, and are not on systemic immunosuppressive therapy.
- - Major cardiac surgery within 8 weeks prior to the first dose of study drug; all other
major surgery within 4 weeks prior to the first dose of study drug.
- - Subjects with following physical and laboratory test findings:
1.
Absolute neutrophil count < 1 x 109/L without growth factor support within 1 week. 2. Platelets < 75 x 109/L without transfusion support within 3 days for the dose
escalation phase. For the DEC: platelets < 75 x 109/L or < 30 x 109/L if ≥ 50% of
bone marrow nucleated cells were plasma cells without transfusion support within
3 days. 3. Hemoglobin < 8 g/dL without transfusion support within 3 days of screening. 4. 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]
5.
Total bilirubin ≥ 2 x ULN (≥ 3 x ULN if documented Gilbert's syndrome)
6. AST or ALT ≥ 3x ULN. 7. Corrected serum calcium > 13.5 mg/dL.
- - Subjects with known severe hypersensitivity or anaphylaxis to Dexamethasone, any
excipients in Elotuzumab, formulation or recombinant protein, or any monoclonal
antibody.
- - Use of strong CYP3A inhibitors within 2 weeks or 5 half-lives of the drug whichever is
shorter prior to the first dose of study drug during the dose escalation portion of
the study.
(In the dose expansion part, strong CYP3A inhibitors may be allowed with
appropriate dose adjustments based on the results of the itraconazole drug-drug
interaction study. The concomitant use of strong CYP3A induces should be avoided.)
- - Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness
