A Study Comparing Anitocabtagene Autoleucel to Standard of Care Therapy in Participants With Relapsed/ Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT06413498
- Lead Sponsor
- Kite, A Gilead Company
- Brief Summary
The goal of this study (iMMagine-3) is to compare the study drug, anitocabtagene autoleucel to standard of care therapy (SOCT) in participants with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an immunomodulatory drug.
The primary objective of this study is to compare the efficacy of anitocabtagene autoleucel versus SOCT in participants with RRMM as measured by progression-free survival (PFS) per blinded independent review committee (IRC).
- Detailed Description
After completing the treatment period, all participants who will receive anitocabtagene autoleucel, will be followed in the post-treatment follow-up period. Thereafter, participants will transition to a separate long-term follow-up study (KT-US-982-5968) to continue follow-up out to 15 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 450
-
Documented historical diagnosis of multiple myeloma (MM)
-
Received 1 to 3 prior lines of antimyeloma therapy, including an immunomodulatory drug (IMiD) and an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb). A minimum of 2 consecutive cycles of an IMiD and an anti-CD38 mAb in any prior line of therapy is required. The IMiD and anti-CD38 mAb do not need to be from the same regimen in the prior line(s) of therapy.
-
Documented evidence of progressive disease by IMWG criteria based on the investigator's determination on or within 12 months of the last dose of the last regimen
-
Measurable disease at screening per IMWG, defined as any of the following:
- Serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
- Light chain MM without measurable disease in the serum or urine: serum free light chain ≥ 10 mg/dL and abnormal serum free light chain ratio
-
Only individuals who are candidates to receive at least 1 of the 4 SOCT regimens (PVd, DPd, KDd, or Kd), as determined by the investigator, should be considered for this study
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
Key
- Prior B-cell maturation antigen (BCMA)-targeted therapy
- Prior T-cell engager therapy
- Prior CAR therapy or other genetically modified T-cell therapy
- Active or prior history of central nervous system (CNS) or meningeal involvement of MM
- Cardiac atrial or cardiac ventricular MM involvement
- History of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
- Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. Myelodysplastic syndrome (even without ongoing treatment) is not permitted.
- Prior auto-SCT within 12 weeks before randomization
- Prior allogeneic stem cell transplant (allo-SCT)
- High-dose (eg, cumulative > 70 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days before randomization
- Live vaccine ≤ 4 weeks before randomization
- Contraindication to fludarabine or cyclophosphamide
- History of allergy or hypersensitivity to any study agent or study drug components. Individuals with a history of severe hypersensitivity reaction to dimethyl sulfoxide (DMSO) are excluded.
- Life expectancy < 12 weeks
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Anitocabtagene Autoleucel Anitocabtagene Autoleucel Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1. Anitocabtagene Autoleucel Cyclophosphamide Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1. Anitocabtagene Autoleucel Fludarabine Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1. Standard of Care Therapy (SOCT) Dexamethasone Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles) Standard of Care Therapy (SOCT) Pomalidomide Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles) Standard of Care Therapy (SOCT) Bortezomib Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles) Standard of Care Therapy (SOCT) Daratumumab Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles) Standard of Care Therapy (SOCT) Carfilzomib Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles)
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to 4 years PFS is defined as the time from randomization to disease progression per International Myeloma Working Group (IMWG) criteria as determined by independent review committee (IRC), or death due to any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Complete Response (CR) Rate (CR/ Stringent Complete Response (sCR)) Up to 4 years CR rate is defined as the proportion of participants who achieved a best overall response of CR or sCR per IMWG criteria as determined by IRC.
MRD-negative CR/sCR Up to 7 years MRD-negative CR/sCR is defined as the proportion of participants achieving MRD-negative CR/sCR until disease progression, subsequent anti-MM therapy, or death.
Overall survival (OS) Up to 7 years OS is defined as the time from randomization to death due to any cause.
Overall Response Rate (ORR) Up to 7 years ORR is defined as the proportion of participants who achieve a best overall response of at least partial response (PR) or better (sCR, CR, very good partial response (VGPR), or PR) per IMWG criteria.
MRD-negative VGPR+ Up to 7 years MRD-negative VGPR+ is defined as the proportion of participants achieving MRD negativity and sCR/CR/VGPR until disease progression, subsequent anti-MM therapy, or death.
Time to Next Treatment Up to 7 years Time to next treatment is defined as the time from randomization to the start of subsequent anti-MM therapy or death from any cause, whichever occurs first.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) First dose up to 7 years Change From Baseline in the EORTC - Multiple Myeloma Module (EORTC QLQ-MY20) Score Up to 7 years The EORTC QLQ-MY20 has 20 items across 4 independent subscales; 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment) with a recall period of one week. Scores from each subscale are transformed from 0 to 100. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.
Percentage of Participants Using Healthcare Resources Up to 7 years Healthcare resource utilization will be assessed based on the numbers of hospitalizations, intensive care unit (ICU) inpatient days, and non-ICU inpatient days.
Overall Minimal Residual Disease (MRD) Negativity Up to 7 years Overall MRD negativity, defined as the proportion of any MRD negativity in participants with bone marrow aspirate (\< 1 in 10\^5 nucleated cells per IMWG criteria using next-generation sequencing (NGS)) at any time after randomization until disease progression, subsequent anti-multiple myeloma (MM) therapy, or death.
Sustained MRD Negativity Up to 7 years Sustained MRD negativity is defined as the proportion of participants remaining MRD-negative at the 10\^-5 sensitivity threshold for the specified number of months starting from the first MRD-negative assessment date to the last MRD-negative assessment date prior to disease progression, subsequent anti-MM therapy, or death. Duration may include ≥ 12 months. Sustained MRD negativity will be evaluated for overall MRD negativity, MRD-negative CR/sCR, and MRD-negative VGPR+.
Duration of Response (DOR) Up to 7 years DOR is derived only among participants who experience an overall response (sCR, CR, VGPR, or PR) per IMWG criteria and is defined as the time from first overall response to disease progression per IMWG criteria, or death from any cause, whichever occurs first.
Percentage of Participants With Presence of Replication-Competent Lentivirus (Anitocabtagene Autoleucel Arm) Up to 7 years Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score Up to 7 years The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) single item symptoms scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a high level of symptoms.
Time to Progression Up to 7 years Time to progression is defined as the time from randomization to the first documented disease progression per IMWG criteria, or death due to disease progression, whichever occurs first.
Percentage of Participants With Anti-Anitocabtagene Autoleucel CAR Antibodies (Anitocabtagene Autoleucel Arm) Up to 7 years Change From Baseline in the European Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Score Up to 7 years The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). The total score for EQ-5D-5L index is presented on a range where higher scores indicate better outcome. A positive change from Baseline indicates improvement.
Trial Locations
- Locations (51)
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Hospitalier Universitaire de Nantes
🇫🇷Nantes, France
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UC San Diego Moores Cancer Center
🇺🇸San Diego, California, United States
University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
UCLA Department of Medicine-Hematology/Oncology
🇺🇸Santa Monica, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Norton Cancer Institute, St. Matthews Campus
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Corewell Health - Lemmen-Holton Cancer Pavilion
🇺🇸Grand Rapids, Michigan, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Royal North Shore Hospital
🇦🇺St. Leonards, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Epworth HealthCare
🇦🇺Richmond, Victoria, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Ordensklinikum Linz GmbH Elisabethinen, Hamatologie mit Stammzelltransplantation, Hamostaseologie und medizinische Onkologie
🇦🇹Linz, Austria
University Hospital St. Poelten, Department of Internal Medicine I
🇦🇹St. Poelten, Austria
UZ Leuven
🇧🇪Flemish Brabant, Belgium
UZ Gent
🇧🇪Gent Oost-Vlaanderen, Belgium
CHU de Lille- Hopital Claude Huriez
🇫🇷Lille, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
CHU de Rennes
🇫🇷Rennes, France
CHU de Toulouse. IUCT Oncopole
🇫🇷Toulouse, France
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, MI, Italy
IRCCS AOU di Bologna
🇮🇹Bologna, Italy
Hyogo Medical University Hospital
🇯🇵Hyogo, Japan
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Complejo Asistencial Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Seville, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
University Hospitals Bristol NHS Foundation Trust, Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Leeds Teaching Hospitals NHS Trust, St James's University Hospital
🇬🇧Leeds, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
Newcastle Hospitals NHS Foundation Trust, Freeman Hospital
🇬🇧Newcastle, United Kingdom