search
Back to results

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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Biospecimen Collection
Bone Marrow Aspiration
Computed Tomography
Mezigdomide
Positron Emission Tomography
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • City of Hope Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (mezigdomide)

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of adverse events
Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0). Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

Secondary Outcome Measures

Overall response rate
Will be defined as the proportion of subjects with a best overall response of stringent complete response (sCR), CR, very good partial response (VGPR), or partial response (PR), as determined by the investigator according to standard International Myeloma Working Group (IMWG) response criteria.
Complete response rate
Will be defined as the proportion of patients meeting the criteria CR or sCR.
Overall survival
Progression free survival
Will be determined by the investigator according to standard IMWG response criteria.
Time to progression
Duration of response
Will be determined by the investigator according to standard IMWG response criteria.

Full Information

First Posted
September 15, 2023
Last Updated
September 21, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT06048250
Brief Title
Mezigdomide (CC-92480) Post Idecabtagene Vicleucel in Treating Patients With Relapsed Multiple Myeloma
Official Title
A Phase 1 Study of Mezigdomide (CC-92480) and Dexamethasone Post Idecabtagene Vicleucel in Relapsed Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2023 (Anticipated)
Primary Completion Date
July 12, 2025 (Anticipated)
Study Completion Date
July 12, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (mezigdomide)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo blood sample collection
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Aspiration
Intervention Description
Undergo bone marrow aspiration
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT
Intervention Type
Biological
Intervention Name(s)
Mezigdomide
Other Intervention Name(s)
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
Intervention Description
Receive PO
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
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
Intervention Description
Undergo PET/CT
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0). Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Overall response rate
Description
Will be defined as the proportion of subjects with a best overall response of stringent complete response (sCR), CR, very good partial response (VGPR), or partial response (PR), as determined by the investigator according to standard International Myeloma Working Group (IMWG) response criteria.
Time Frame
Up to 2 years
Title
Complete response rate
Description
Will be defined as the proportion of patients meeting the criteria CR or sCR.
Time Frame
Up to 2 years
Title
Overall survival
Time Frame
From first day of treatment to time of death due to any cause, assessed up to 2 years
Title
Progression free survival
Description
Will be determined by the investigator according to standard IMWG response criteria.
Time Frame
From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 2 years
Title
Time to progression
Time Frame
From first day of treatment to the first observation of disease progression or death due to disease, assessed up to 2 years
Title
Duration of response
Description
Will be determined by the investigator according to standard IMWG response criteria.
Time Frame
From first response documented until disease progression, assessed up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Murali Janakiram
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Murali Janakiram
Phone
626-256-4673
Ext
85200
Email
MJANAKIRAM@COH.ORG
First Name & Middle Initial & Last Name & Degree
Murali Janakiram

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs