Mezigdomide (CC-92480) Post Idecabtagene Vicleucel in Treating Patients With Relapsed Multiple Myeloma

NCT ID: NCT06048250

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-09
• Study Completion Date: 2026-03-21

Brief Summary

This phase I trial studies the safety, side effects, best dose and effectiveness of mezigdomide (CC-92480) when given after idecabtagene vicleucel (Abecma chimeric antigen receptor [CAR] T-cell therapy) in patients with multiple myeloma that has come back after a period of improvement (relapsed). 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. Giving mezigdomide after Abecma CAR T cell therapy may extending the amount of time that the CAR T cells persist in the body in patients with relapsed multiple myeloma.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the safety and tolerability of mezigdomide (CC-92480) given post idecabtagene vicleucel when administered as a continued therapy.

SECONDARY OBJECTIVES:

I. To evaluate the anti-tumor activity of mezigdomide (CC-92480) when administered post idecabtagene vicleucel.

II. To determine the persistence of CAR T cells at day 90 (D90), day 180 (D180), and day 365 (D365) after start of mezigdomide (CC-92480) therapy.

EXPLORATORY OBJECTIVES:

I. To assess levels of serum BCMA monthly at day 1 of every cycle. II. To assess the effects of mezigdomide (CC-92480) on non-cancer immune cells in the peripheral blood and bone marrow samples.

OUTLINE: This is a dose-escalation study of mezigdomide.

Starting between 30 and 90 days after infusion of idecabtagene vicleucel, patients receive mezigdomide orally (PO) on days 1-21 or days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)/computed tomography (CT) during screening. Patients also undergo bone marrow aspiration and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days, every 3 months within 1 year of start of treatment, and then every 6 months until progression or for up to 2 years.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (mezigdomide)

Starting between 30 and 90 days after infusion of idecabtagene vicleucel, patients receive mezigdomide PO on days 1-21 or days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT during screening. Patients also undergo bone marrow aspiration and blood sample collection throughout the study.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Bone Marrow Aspiration

Intervention Type: PROCEDURE

Undergo bone marrow aspiration

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT

Mezigdomide

Intervention Type: BIOLOGICAL

Receive PO

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET/CT

Interventions

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type: PROCEDURE

Computed Tomography

Undergo CT

Intervention Type: PROCEDURE

Mezigdomide

Receive PO

Intervention Type: BIOLOGICAL

Positron Emission Tomography

Undergo PET/CT

Intervention Type: PROCEDURE

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; CT; CT Scan; tomography; BMS 986348; BMS-986348; BMS986348; CC 92480; CC-92480; CELMoD CC-92480; Cereblon E3 Ligase Modulation Drug CC-92480; Cereblon E3 Ubiquitin Ligase Modulating Agent CC-92480; Cereblon Modulator CC-92480; Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron emission tomography (procedure); Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT

Eligibility Criteria

Inclusion Criteria

• Documented informed consent of the participant and/or legally authorized representative.

• Assent, when appropriate, will be obtained per institutional guidelines
• Age: >= 18 years
• Eastern Cooperative Oncology Group (ECOG) =< 2
• Diagnosis of multiple myeloma
• Subject must have received at least 4 prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody
• Receipt of commercially available idecabtagene vicleucel (Abecma) according to FDA approved US Prescribing Information. Note: Patients who received non-conforming Abecma who were originally prescribed Abecma according to the FDA approved label may be considered for inclusion per the investigators discretion. Subject must be between day 30 and day 90 post receipt of idecabtagene vicleucel
• Subject must have experienced at least a stable disease in response to idecabtagene vicleucel
• Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy, including idecabtagene vicleucel
• Absolute neutrophil count (ANC) >= 1,500/mm^3 without the use of filgrastim in the previous 3 days (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)

• Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• Platelets >= 75,000/mm^3 without platelet transfusion in the previous 3 days. (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)

• Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has known Gilbert's disease) (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated).

• Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• Aspartate aminotransferase (AST) =< 3 x ULN (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated).

• Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• Alanine transaminase (ALT) =< 3 x ULN (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated).

• Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• Alkaline phosphatase =< 5 x ULN (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated).

• Two repeat tests are allowed. If the repeat test satisfies criteria, the participant may enroll provided all other criteria are met
• Oxygen saturation > 92% on room air (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (To be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• Agreement by females of childbearing potential and males to follow the guidelines of the mezigdomide (CC-92480) pregnancy prevention plan

Exclusion Criteria

• Prior exposure to mezigdomide (CC-92480)
• Current or planned use of other therapies other than mezigdomide (CC-92480)
• Patients who are currently receiving or likely to require systemic immunosuppressive therapy. Physiologic replacement of steroids (=< 5.0 mg/day prednisone or equivalent) is allowed
• Concomitant use of CYP3A4/5 inhibitors and inducers
• Concomitant use of proton pump inhibitors
• Evidence of relapse as evaluated by the treating physician or study investigator
• Active central nervous system involvement
• Ongoing toxicities associated with cytokine release syndrome (CRS) or Immune effector cell-associated neurotoxicity syndrome (ICANS) from CAR T cell therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Coronavirus disease 2019 (COVID-19) positive, as assessed by a polymerase chain reaction (PCR) test or active uncontrolled infections (defined as active antibiotic use within 7 days of starting the investigational drug)
• If human immunodeficiency virus (HIV) positive: CD4+ T cell count < 200
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Murali Janakiram

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Murali Janakiram

Role: primary

MJANAKIRAM@COH.ORG

626-256-4673 ext. 85200

Other Identifiers

NCI-2023-06771

Identifier Type: REGISTRY

Identifier Source: secondary_id

22143

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22143

Identifier Type: -

Identifier Source: org_study_id