Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, CAR-T, ddBCMA, BCMA
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.
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.
Interventions
A single infusion of CAR+ transduced autologous T cells
DRUGCyclophosphamide
Administered intravenously
DRUGFludarabine
Administered intravenously
DRUGPomalidomide
Tablet administered orally
DRUGBortezomib
Administered intravenously or subcutaneously
DRUGDexamethasone
Tablet administered orally
DRUGDaratumumab
Administered intravenously or subcutaneously
DRUGCarfilzomib
Administered intravenously
Sponsors
Kite, A Gilead Company
Arcellx, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 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
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Minimal Residual Disease (MRD) Complete Response (CR) Rate at 9 Months | Up to 9 months | Minimal MRD is defined as the proportion of participants achieving CR/stringent CR (sCR) and MRD-negative status at 9 months. MRD negativity at 9 months is defined as negative MRD value at 9 months (± 3 months) in bone marrow assessment (\< 1 in 105 nucleated cells per IMWG criteria using NGS) (Kumar 2016). CR/sCR per IMWG criteria is determined by IRC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Overall 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. |
| 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 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. |
| 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. |
| 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. |
| 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. |
| 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 | — |
| Percentage of Participants With Anti-Anitocabtagene Autoleucel CAR Antibodies (Anitocabtagene Autoleucel Arm) | Up to 7 years | — |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Italy, Japan, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
CONTACTMedical Information
STUDY_DIRECTORKite Study Director
Kite, A Gilead Company
Outcome results
None listed