Trial Title:
Elotuzumab, CC-92480, and Dexamethasone for the Treatment of Relapsed or Refractory Myeloma After CD38- and BCMA-Targeted Therapies
NCT ID:
NCT05981209
Condition:
Recurrent Multiple Myeloma
Refractory Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Dexamethasone acetate
Elotuzumab
Ichthammol
BB 1101
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow biopsy and aspiration
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy and aspiration
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Given IV or PO
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
Aacidexam
Other name:
Adexone
Other name:
Aknichthol Dexa
Other name:
Alba-Dex
Other name:
Alin
Other name:
Alin Depot
Other name:
Alin Oftalmico
Other name:
Amplidermis
Other name:
Anemul mono
Other name:
Auricularum
Other name:
Auxiloson
Other name:
Baycadron
Other name:
Baycuten
Other name:
Baycuten N
Other name:
Cortidexason
Other name:
Cortisumman
Other name:
Decacort
Other name:
Decadrol
Other name:
Decadron
Other name:
Decadron DP
Other name:
Decalix
Other name:
Decameth
Other name:
Decasone R.p.
Other name:
Dectancyl
Other name:
Dekacort
Other name:
Deltafluorene
Other name:
Deronil
Other name:
Desamethasone
Other name:
Desameton
Other name:
Dexa-Mamallet
Other name:
Dexa-Rhinosan
Other name:
Dexa-Scheroson
Other name:
Dexa-sine
Other name:
Dexacortal
Other name:
Dexacortin
Other name:
Dexafarma
Other name:
Dexafluorene
Other name:
Dexalocal
Other name:
Dexamecortin
Other name:
Dexameth
Other name:
Dexamethasone Intensol
Other name:
Dexamethasonum
Other name:
Dexamonozon
Other name:
Dexapos
Other name:
Dexinoral
Other name:
Dexone
Other name:
Dinormon
Other name:
Dxevo
Other name:
Fluorodelta
Other name:
Fortecortin
Other name:
Gammacorten
Other name:
Hemady
Other name:
Hexadecadrol
Other name:
Hexadrol
Other name:
Lokalison-F
Other name:
Loverine
Other name:
Methylfluorprednisolone
Other name:
Millicorten
Other name:
Mymethasone
Other name:
Orgadrone
Other name:
Spersadex
Other name:
TaperDex
Other name:
Visumetazone
Other name:
ZoDex
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
EC
Intervention type:
Biological
Intervention name:
Elotuzumab
Description:
Given IV
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
BMS-901608
Other name:
Empliciti
Other name:
HuLuc-63
Other name:
HuLuc63
Other name:
PDL-063
Other name:
PDL063
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Biological
Intervention name:
Mezigdomide
Description:
Given PO
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
BMS 986348
Other name:
BMS-986348
Other name:
BMS986348
Other name:
CC 92480
Other name:
CC-92480
Other name:
CELMoD CC-92480
Other name:
Cereblon E3 Ligase Modulation Drug CC-92480
Other name:
Cereblon E3 Ubiquitin Ligase Modulating Agent CC-92480
Other name:
Cereblon Modulator CC-92480
Intervention type:
Procedure
Intervention name:
X-Ray Imaging
Description:
Undergo x-ray imaging
Arm group label:
Treatment (elotuzumab, CC-92480, dexamethasone)
Other name:
Conventional X-Ray
Other name:
Diagnostic Radiology
Other name:
Medical Imaging, X-Ray
Other name:
Plain film radiographs
Other name:
Radiographic Imaging
Other name:
Radiographic imaging procedure (procedure)
Other name:
Radiography
Other name:
RG
Other name:
Static X-Ray
Other name:
X-Ray
Summary:
This phase Ib trial tests the safety, side effects, and best dose of CC-92480 in
combination with elotuzumab and dexamethasone in treating patients with multiple myeloma
that has come back after a period of improvement (relapsed) or that does not respond to
treatment or has not responded to previous treatment (refractory). Multiple myeloma (MM)
remains the second most common hematologic malignancy in the United States. A number of
therapies have been approved for patients with MM, including CD38- and B-cell maturating
antigen (BCMA)-targeted therapies (antibody and plasma cell treatments that help the
body's immune system to kill cancer cells); however, patients will often relapse and
become refractory to these therapies. Because of this, it is important to identify
effective treatment options for patients progressing on anti-CD38 therapy and
BCMA-directed therapies. Elotuzumab is a humanized IgG1 monoclonal antibody, which is a
type of protein that can bind to other target cells to prevent them from working the way
they should or cause them to act differently. Elotuzumab works by targeting a protein
called SLAMF7, which is present on myeloma cells, and makes it easier for the immune
system to target the cancer. CC-92480 works by binding to a protein called CRBN that
triggers the breakdown of proteins: Ikaros and Aiolos, leading to cell death in multiple
myeloma cells. Dexamethasone is a synthetic adrenocortical steroid, or steroid normally
naturally made by the adrenal gland in the brain which has been produced in a laboratory,
that helps to regulate the amount of different chemicals and water that are being
processed by the kidneys. It is also used in patients with myeloma to help treat their
disease. The combination of CC-92480 with elotuzumab and dexamethasone may be a safe and
effective treatment when given to patients with relapsed or recurrent MM.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the safety and tolerability of elotuzumab, mezigdomide (CC-92480), and
dexamethasone (E480d) in patients with relapsed/refractory multiple myeloma (RRMM) who
have received >= 2 prior regimens including CD38- and BCMA-targeted therapies.
SECONDARY OBJECTIVES:
I. Determine the time to response (TTR), the duration of response (DOR), very good
partial response [VGPR] or better and complete response [CR] rates, progression free
survival (PFS) at 1 year, and overall survival (OS) at 1 year.
II. Check minimal residual disease (MRD) negativity rates by next generation sequencing
in patients who are suspected of attaining a complete response (CR).
III. Correlative studies will include changes in lymphocyte subsets with therapy,
immunophenotype of MM cells, and expression of CRBN, Ikaros, and Aiolos.
IV. Quality of life (QOL) will be assessed.
OUTLINE: This is a dose-escalation study of CC-92480, followed by a dose-expansion study.
Patients receive elotuzumab intravenously (IV) on days 1, 8, 15, and 22 of cycles 1 and 2
and then on day 1 of each subsequent cycle. Patients also receive CC-92480 orally (PO) on
days 1-21 of each cycle and dexamethasone IV or PO on days 1, 8, 15, and 22 of each
cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable
toxicity. Patients may undergo an echocardiography (ECHO) during screening and undergo
magnetic resonance imaging (MRI), computed tomography (CT), or x-ray imaging during
screening and on study as clinically indicated. Patients also undergo blood sample
collection as well as bone marrow biopsy and aspiration during screening and on study.
After completion of study treatment, patients are followed up at 30 and 60 days and then
every 12 weeks for up to 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients 18 years of age or older with evidence of relapsed or refractory disease as
defined by International Myeloma Working Group (IMWG) criteria and measurable
disease as defined by any of the following:
- Serum M-protein >= 1.0 g/dl
- Urine monoclonal protein >= 200 mg/24h
- Involved free light chain (FLC) level >= 10mg/dl (>= 100mg/l) and an abnormal
serum free light chain ratio (< 0.26, or > 1.65)
- Patients must have had at least 2 prior lines of therapy including lenalidomide,
proteasome inhibitor (PI), anti-CD38 directed antibody, and BCMA-targeted therapy
- Prior elotuzumab is permitted but patients with progressive disease (PD) as
best reponse on elotuzumab are excluded; at least 6 months must have lapsed
from prior elotuzumab exposure
- Patients must have hemoglobin >= 7g/dL
- Absolute neutrophil count (ANC) >= 1000/uL
- Platelets >= 70,000/uL
- If plasma cell percentage on bone marrow biopsy aspirate or core is > 30%,
platelet requirement will be adjusted to 50,000/ul
- Total bilirubin =< 1.5 x the upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase
< 2.5 x the ULN
- Calculated creatinine clearance of >= 45ml/min using Modification of Diet in Renal
Disease (MDRD) formula
- Left ventricular ejection fraction >= 30%; baseline echocardiography (ECHO) is not
required if ECHO was done within the preceding one year and patients do not have new
signs/symptoms suggestive of heart failure
- No uncontrolled arrhythmias
- No New York Heart Association class III-IV heart failure
- 12-lead electrocardiogram (ECG) with QT interval calculated by Fridericia formula
(QTcF) interval of =< 470 msec
- Patient must be able to swallow capsule or tablet
- Patients must provide informed consent
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status
(PS) score of < 2
- Women of child bearing potential (WOCBP) must commit to either abstain continuously
from heterosexual sexual intercourse or to use 2 methods of reliable birth control
simultaneously. This includes one highly effective form of contraception (tubal
ligation, intrauterine device [IUD], hormonal [birth control pills, injections,
hormonal patches, vaginal rings or implants] or partner's vasectomy) and one
additional effective contraceptive method (male latex or synthetic condom,
diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing and
continue to 6 months after study treatment ending. Reliable contraception is
indicated even where there has been a history of infertility, unless due to
hysterectomy
- Investigators shall counsel WOCBP and male participants who are sexually active with
WOCBP on the importance of pregnancy prevention and the implications of an
unexpected pregnancy
- A negative pregnancy test will be required for all WOCBP within 24 hours before
starting treatment drugs
- Breast feeding is not permitted
- Male patients must agree to use an adequate method of contraception (latex or
synthetic condom) for the duration of the study and up to 6 months after study
treatment ending
- Criteria also applies to azoospermic males
- Males should refrain from sperm donation during this time and continue for 6 months
after study treatment ending
Exclusion Criteria:
- Patients with Waldenstrom macroglobulinemia, primary amyloid light chain (AL)
amyloidosis, primary plasma cell leukemia, or polyneuropathy, organomegaly,
endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome
- Patients with secondary plasma cell leukemia are permitted
- Patients with peripheral neuropathy > National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) grade 2, or grade 2 peripheral
neuropathy with pain
- Patients receiving concurrent corticosteroids at the time protocol therapy is
initiated other than for physiologic maintenance treatment
- Concurrent use of complementary or alternative medicines that would confound the
interpretation of toxicities and antitumor activity of the study drugs
- Patients with history of anaphylaxis or hypersensitivity to elotuzumab,
lenalidomide, or pomalidomide
- Concurrent use of strong CYP3A modulators; concurrent use of proton-pump inhibitors
=< 2 weeks prior to started CC-92480
- Unacceptable respiratory risk factors defined by any one of the following criteria:
- Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in
1 second (FEV1) less than 50% of predicted normal
- Moderate or severe persistent asthma within the past 2 years, or currently has
uncontrolled asthma of any classification
- Unacceptable cardiac risk factors defined by any of the following criteria:
- Left ventricular ejection fraction < 30%
- Complete left bundle branch, bifascicular block or clinically significant
abnormal electrocardiogram (EKG) finding at screening
- A prolongation of QT interval on screening ECG as defined by repeated
demonstration of a QTc interval > 470 msec using Fridericia's QT correction
formula; a family history of long QT syndrome
- Myocardial infarction within 6 months
- Unstable angina
- Patients who have received targeted or investigational agents within 2 weeks or
within 5 half-lives of the agent and active metabolites (whichever is shorter) and
who have not recovered from side effects of those therapies
- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from the side-effects of surgery
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis
C; baseline testing for HIV and hepatitis C is not required
- Patients with active hepatitis B (defined as hepatitis B surface antigen [HBsAg]+);
hepatitis b virus (HBV) screening is required prior to beginning therapy
- Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-,
hepatitis B virus surface antibody [anti-HBs]+, hepatitis B virus core antibody
[anti-HBc]-)
- Non-active hepatitis B (HBsAg-, anti-HBs+, anti-HBc+) may only be enrolled
following approval by the sponsor after consideration of risk of reactivation
(additional screening and monitoring for hepatitis B and consultation with a
liver disease specialist may be required)
- Patients with a history of another primary malignancy that is currently clinically
significant or currently requires active intervention, other than non-melanoma skin
cancer and carcinoma in situ of the cervix or breast, should not be enrolled
- Patients with a history of gastrointestinal surgery or other procedure that might,
in the opinion of the investigator(s), interfere with the absorption or swallowing
of the study drugs
- Patients with any significant history of non-compliance to medical regimens or
unwilling or unable to comply with the instructions given to them by the study staff
- Any other medical condition, including mental illness or substance abuse, deemed by
the investigator(s) to likely interfere with the patient's ability to sign informed
consent, cooperate and participate in the study, or interfere with the
interpretation of the results
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Abdullah M. Khan, MBBS, MSc
Phone:
614-293-3196
Email:
Abdullah.Khan@osumc.edu
Investigator:
Last name:
Abdullah M. Khan, MBBS, MSc
Email:
Principal Investigator
Start date:
December 21, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Abdullah Khan
Agency class:
Other
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05981209
http://cancer.osu.edu
