RECRUITING

Elotuzumab, CC-92480, and Dexamethasone for the Treatment of Relapsed or Refractory Myeloma After CD38- and BCMA-Targeted Therapies

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Conditions

Recurrent Multiple MyelomaRefractory Multiple Myeloma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase 1b Study to Assess Safety and Efficacy of Elotuzumab, CC-92480, and Dexamethasone in Relapsed/Refractory Myeloma After CD38- and BCMA-Targeted Therapies

Quick Facts

Study Start:2023-12-21
Study Completion:2025-12-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05981209

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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:
  2. * Serum M-protein \>= 1.0 g/dl
  3. * Urine monoclonal protein \>= 200 mg/24h
  4. * Involved free light chain (FLC) level \>= 10mg/dl (\>= 100mg/l) and an abnormal serum free light chain ratio (\< 0.26, or \> 1.65)
  5. * Patients must have had at least 2 prior lines of therapy including lenalidomide, proteasome inhibitor (PI), anti-CD38 directed antibody, and BCMA-targeted therapy
  6. * 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
  7. * Patients must have hemoglobin \>= 7g/dL
  8. * Absolute neutrophil count (ANC) \>= 1000/uL
  9. * Platelets \>= 70,000/uL
  10. * If plasma cell percentage on bone marrow biopsy aspirate or core is \> 30%, platelet requirement will be adjusted to 50,000/ul
  11. * Total bilirubin =\< 1.5 x the upper limit of normal (ULN)
  12. * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase \< 2.5 x the ULN
  13. * Calculated creatinine clearance of \>= 45ml/min using Modification of Diet in Renal Disease (MDRD) formula
  14. * 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
  15. * No uncontrolled arrhythmias
  16. * No New York Heart Association class III-IV heart failure
  17. * 12-lead electrocardiogram (ECG) with QT interval calculated by Fridericia formula (QTcF) interval of =\< 470 msec
  18. * Patient must be able to swallow capsule or tablet
  19. * Patients must provide informed consent
  20. * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of \< 2
  21. * 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
  22. * 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
  23. * A negative pregnancy test will be required for all WOCBP within 24 hours before starting treatment drugs
  24. * Breast feeding is not permitted
  25. * 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
  26. * Criteria also applies to azoospermic males
  27. * Males should refrain from sperm donation during this time and continue for 6 months after study treatment ending
  1. * 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
  2. * Patients with secondary plasma cell leukemia are permitted
  3. * Patients with peripheral neuropathy \> National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2, or grade 2 peripheral neuropathy with pain
  4. * Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
  5. * Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
  6. * Patients with history of anaphylaxis or hypersensitivity to elotuzumab, lenalidomide, or pomalidomide
  7. * Concurrent use of strong CYP3A modulators; concurrent use of proton-pump inhibitors =\< 2 weeks prior to started CC-92480
  8. * Unacceptable respiratory risk factors defined by any one of the following criteria:
  9. * Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than 50% of predicted normal
  10. * Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
  11. * Unacceptable cardiac risk factors defined by any of the following criteria:
  12. * Left ventricular ejection fraction \< 30%
  13. * Complete left bundle branch, bifascicular block or clinically significant abnormal electrocardiogram (EKG) finding at screening
  14. * 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
  15. * Myocardial infarction within 6 months
  16. * Unstable angina
  17. * 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
  18. * Patients who have undergone major surgery =\< 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
  19. * Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  20. * Patients with active hepatitis B (defined as hepatitis B surface antigen \[HBsAg\]+); hepatitis b virus (HBV) screening is required prior to beginning therapy
  21. * Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, hepatitis B virus surface antibody \[anti-HBs\]+, hepatitis B virus core antibody \[anti-HBc\]-)
  22. * 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)
  23. * 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
  24. * 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
  25. * 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
  26. * 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

Contacts and Locations

Study Contact

The Ohio State Comprehensive Cancer Center
CONTACT
800-293-5066
OSUCCCClinicaltrials@osumc.edu

Principal Investigator

Abdullah M Khan, MBBS, MSc
PRINCIPAL_INVESTIGATOR
Ohio State University Comprehensive Cancer Center

Study Locations (Sites)

Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
United States

Collaborators and Investigators

Sponsor: Abdullah Khan

  • Abdullah M Khan, MBBS, MSc, PRINCIPAL_INVESTIGATOR, Ohio State University Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-21
Study Completion Date2025-12-31

Study Record Updates

Study Start Date2023-12-21
Study Completion Date2025-12-31

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Multiple Myeloma
  • Refractory Multiple Myeloma