Phase 1/2 Trial of Elotuzumab, Daratumumab, Iberdomide, and Dexamethasone for Relapsed Multiple Myeloma

Status: Recruiting
Location: See location...
Intervention Type: Procedure, Biological, Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This phase I/II trial tests the safety, side effects, and best dose of iberdomide and how well it works in combination with daratumumab, elotuzumab, and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed). Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Elotuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving iberdomide in combination with daratumumab, elotuzumab, and dexamethasone may be safe, tolerable and/or effective in patients with relapsed multiple myeloma.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Age ≥ 18 years at the time of signing the informed consent form (ICF).

• Diagnosis of relapsed multiple myeloma with ≤ 3 prior lines of therapy including treatment with proteasome inhibitors (i.e., ixazomib, carfilzomib, bortezomib), immunomodulatory imide drugs (i.e., lenalidomide, pomalidomide), and anti-CD38 drugs (i.e., daratumumab, isatuximab). Patients are required to have received a proteasome inhibitor, immunomodulatory imide drug, or combination of the two drug classes during first-line treatment.

‣ Note: Prior treatment with iberdomide is not allowed. Patients should not be refractory simultaneously to all other drugs in the combination.

• Measurable disease.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2.

• Hemoglobin ≥ 8.0 g/dL (obtained ≤14 days prior to registration).

• Absolute neutrophil count (ANC) ≥ 1000/m\^3 (obtained ≤14 days prior to registration).

• Platelet count ≥ 50,000/mm\^3. Note: It is not permissible to transfuse subjects to achieve minimum platelet counts (obtained ≤14 days prior to registration).

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3 x ULN for patients with Gilbert's syndrome) (obtained ≤14 days prior to registration).

• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2 x ULN and alkaline phosphatase ≤ 1.5 x ULN (obtained ≤14 days prior to registration).

• Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault (obtained ≤14 days prior to registration).

• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. Note: A person of childbearing potential (PCBP) is a person who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) and must:

‣ Have 2 negative pregnancy tests prior to starting study treatment and must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.

⁃ AND

• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment, and for at least 28 days after the last dose of iberdomide, 90 days after the last dose of daratumumab, 7 months after last dose of elotuzumab whichever is longer.

• NOTE: Non-childbearing potential is defined as follows (by other than medical reasons):

‣ ≥ 45 years of age and has not had menses for \> 24 months.

⁃ Patients who have been amenorrhoeic for \< 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation.

⁃ Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.

• Willingness to follow Pregnancy Prevention Program requirements:

• Persons of childbearing potential must agree to use a contraceptive method that is highly effective (with a failure rate of \< 1% per year), preferably with low user dependency, during the intervention period and for at least 7 months after the last dose of study intervention. These patients must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period.

• Persons able to father a child must agree that during the treatment intervention period and for 6 months after the last dose of study treatment (to allow for clearance of any altered sperm), the participant will:

‣ Refrain from donating sperm while on study treatment, during dose interruptions and for at least 6 months following last dose of study treatment, PLUS either:

⁃ Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR,

⁃ Must agree to use contraception/barrier such as a male condom (even if they have undergone successful vasectomy), and when having sexual intercourse with a person of childbearing potential who is not currently pregnant his partner will use an additional highly effective contraceptive method with a failure rate of \< 1% per year.

• Provide written informed consent.

∙ Willingness to provide mandatory bone marrow specimens for correlative research.

∙ Willing and able to adhere to the study visit schedule and other protocol requirements. Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

∙ Willing to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of study treatment.

Locations
United States
Minnesota
Mayo Clinic in Rochester
RECRUITING
Rochester
Contact Information
Primary
Clinical Trials Referral Office
mayocliniccancerstudies@mayo.edu
855-776-0015
Time Frame
Start Date: 2025-03-18
Estimated Completion Date: 2031-04-01
Participants
Target number of participants: 37
Treatments
Experimental: Treatment (iberdomide, daratumumab, elotuzumab, dexamethasone)
Patients receive iberdomide PO QD on days 1-21 of each cycle, daratumumab SC on days 1, 8, 15, 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive elotuzumab IV on days 1, 8, 15, and 22 of cycles 1 and 2, and on day 1 of subsequent cycles and dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12 or at the discretion of the treating physician. Cycles repeat every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy during screening, on study and optionally at disease progression and CT, bone scan, MRI or PET/CT during screening, on study or at the discretion of the treating physician and EOT. Patients may undergo chest x-ray during screening.
Sponsors
Leads: Mayo Clinic

This content was sourced from clinicaltrials.gov