Using mezigdomide after CAR T-cell therapy for relapsed multiple myeloma

A Phase 1 Study of Mezigdomide (CC-92480) and Dexamethasone Post Idecabtagene Vicleucel in Relapsed Multiple Myeloma

This study is testing if a new medication called mezigdomide can help people with relapsed multiple myeloma feel better after receiving CAR T-cell therapy.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: City of Hope Medical Center (other)
• Drugs / interventions: CAR T, prednisone, chimeric antigen receptor
• Locations: 1 site (Duarte, California)
• Trial ID: NCT06048250 on ClinicalTrials.gov

What this trial studies

This phase I trial investigates the safety and effectiveness of mezigdomide (CC-92480) administered after idecabtagene vicleucel (Abecma CAR T-cell therapy) in patients with relapsed multiple myeloma. The study aims to determine the best dose and assess the persistence of CAR T cells in the body over time. Participants will receive mezigdomide orally for up to 12 cycles, with regular monitoring through imaging and blood tests. The trial also explores the impact of mezigdomide on immune cells and levels of serum BCMA.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed multiple myeloma who have received at least four prior lines of therapy and have shown a stable disease response to CAR T-cell therapy.

Not a fit: Patients who have not received idecabtagene vicleucel or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could prolong the effectiveness of CAR T-cell therapy and improve outcomes for patients with relapsed multiple myeloma.

How similar studies have performed: While this approach is novel, previous studies have shown promise in enhancing CAR T-cell therapy outcomes with additional treatments.

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)

Where this trial is running

Duarte, California

• City of Hope Medical Center — Duarte, California, United States (RECRUITING)

Study contacts

• Principal investigator: Murali Janakiram — City of Hope Medical Center

Conditions: Multiple Myeloma