Trial Title:
A Study of Iberdomide (CC-220) in Combination With Elotuzumab and Dexamethasone for Relapsed/Refractory Multiple Myeloma
NCT ID:
NCT05560399
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Elotuzumab
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Part 1 is a dose-finding evaluation of Iberdomide in combination with Elotuzumab and
Dexamethasone at their approved doses for patients with relapsed/refractory multiple
myeloma.
Part 2 of this study is an open-label, single-arm dose expansion cohort that will enroll
additional patients at the recommended maximum tolerated dose of Iberdomide as determined
in Part 1.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Iberdomide
Description:
Route of administration: oral pill. Schedule: Taken Once daily on days 1-21. Dose: will
be tested at 1 mg, 1.3 mg, and 1.6mg. 1mg dose may be reduced to 0.75mg if not tolerated.
Arm group label:
Iberdomide, Elotuzumab and Dexamethasone
Other name:
CC-220
Intervention type:
Drug
Intervention name:
Elotuzumab
Description:
Route of administration: IV Dose: 10 mg/kg for cycles 1 and 2. 20 mg/kg for cycle 3 and
beyond. Schedule: Days 1, 8, 15, and 22 for cycles 1 and 2. Then taken on Day 1 (every 28
days) of each cycle thereafter.
Arm group label:
Iberdomide, Elotuzumab and Dexamethasone
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Route of administration: Oral pill or IV Dose: 36 mg within 24 hrs of day 1 of each cycle
and day 8, 15, and 22 of cycle 1 and 2.
40 mg on days 8, 15, 22 of cycle 3 and all subsequent cycles. (20 mg for > 75 years old).
Schedule: On days that Elotuzumab is administered, Dexamethasone to be taken 28mg orally
(for ≤75 years old) or 8mg orally (for > 75 years old) between 3 and 24 hours before
Elotuzumab plus 8 mg IV between 45 and 90 minutes before Elotuzumab for all patients.
On days that Elotuzumab is not administered but a dose of Dexamethasone is scheduled
(Days 8, 15, and 22 of cycle 3 and all subsequent cycles), 40 mg orally for ≤75 years
older and 20 mg for
Arm group label:
Iberdomide, Elotuzumab and Dexamethasone
Summary:
This is a single-arm, open-label study evaluating the safety, tolerability and efficacy
of Iberdomide (CC-220) in combination with Elotuzumab and Dexamethasone in patients with
RRMM. The researchers hypothesize that the combination of Iberdomide and Elotuzumab will
synergize to promote myeloma cell death, resulting in an overall response rate of at
least 53%, with an acceptable safety profile. Patients will be enrolled in a 3+3 dose
escalation cohort to evaluate the safety of this combination and to establish the MTD
(maximum tolerated dose). The MTD will be the dose for the patients enrolled in dose
expansion cohort. A total maximum of 37 patients will be recruited: maximum 18 patients
will be recruited in the dose escalation phase, followed by an additional 19 patients in
the dose expansion cohort for a total of 25 patients treated at the MTD.
Detailed description:
Part 1 is an open-label, sequential allocation, dose-finding evaluation of the sequential
administration of Iberdomide in combination with Elotuzumab and Dexamethasone at their
approved doses for patients with relapsed/refractory multiple myeloma. This phase will
follow a standard 3+3 design. During this phase, the maximum tolerated dose of Iberdomide
in combination with Elotuzumab and Dexamethasone will be determined and recommended for
the dose expansion cohort.
Part 2 of this study is an open-label, single-arm dose expansion cohort that will enroll
additional patients at the recommended maximum tolerated dose of Iberdomide as determined
in Part 1. Researchers will continue to verify the safety and tolerability of this
combination and examine the anti-myeloma activity of the regimen. In addition to
measuring overall response rate, duration of response, and survival data, researchers
will explore the effect of this combination on the biology of multiple myeloma and the
immune system in order to gain insight into patterns of response that may help predict
patient population most-likely to benefit from this treatment in the future.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Icahn School of Medicine
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Contact:
Last name:
Donna Catamero, MHS
Phone:
617-834-9792
Email:
Donna.Catamero@mssm.edu
Contact backup:
Last name:
Kiran Grover, MPH
Phone:
646-629-3783
Email:
kiran.grover@mssm.edu
Investigator:
Last name:
Samir Parekh
Email:
Principal Investigator
Start date:
February 6, 2023
Completion date:
June 2026
Lead sponsor:
Agency:
Icahn School of Medicine at Mount Sinai
Agency class:
Other
Collaborator:
Agency:
Multiple Myeloma Research Consortium
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Source:
Icahn School of Medicine at Mount Sinai
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05560399
