Newly Diagnosed Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, CAR-T, ddBCMA, BCMA
Brief summary
The goal of this clinical study iMMagine-4 is to compare and assess the safety and effectiveness of anitocabtagene autoleucel versus standard of care therapy (SOCT) in participants with newly diagnosed multiple myeloma (NDMM) who are not eligible for autologous stem cell transplant. The primary objective of this study is to compare the efficacy of anitocabtagene autoleucel versus quadruplet-based SOCT in participants with NDMM who are not eligible for autologous stem cell transplant (auto-SCT).
Detailed description
After completing quadruplet-based induction therapy followed by anitocabtagene autoleucel or continuous maintenance therapy, participants will continue to be followed for disease assessments and outcomes.
Interventions
A single infusion of CAR+ transduced autologous T cells
DRUGDaratumumab
Administered subcutaneously (SC)
DRUGBortezomib
Administered SC
DRUGLenalidomide
Administered orally (PO)
DRUGDexamethasone
Administered PO or intravenously (IV)
DRUGFludarabine
Administered IV
DRUGCyclophosphamide
Administered IV
Sponsors
Kite, A Gilead Company
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: * Determined by the Investigator to be not eligible for auto-SCT * Documented newly diagnosed multiple myeloma (NDMM) according to IMWG diagnostic criteria * Measurable disease at screening per IMWG: 1. Serum M-protein level ≥ 1.0 g/dL; or 2. Urine M-protein level ≥ 200 mg/24 hours; or 3. Serum free light chain (FLC) ≥ 10 mg/dL (100 mg/L) and abnormal serum FLC ratio * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Adequate hematological function * Adequate renal, hepatic, pulmonary, and cardiac function Key
Exclusion criteria
* Any prior anti-MM therapy (including B-cell maturation antigen (BCMA)-directed therapy, CAR T-cell therapy, or genetically modified cells), with the exception of protocol-specified anti-MM stabilizing therapy and palliative radiation * Central nervous system (CNS) or meningeal involvement of MM * History of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or amyloidosis * Active malignancy (other than MM) requiring ongoing treatment for disease control within the last 24 months. * Prior allogeneic stem cell transplant * Any prior systemic treatment or radiotherapy treatment for any cancer other than MM within 24 months before randomization. * Live vaccine ≤ 4 weeks before randomization * Presence or suspicion of infection that is uncontrolled * History or presence of intracranial or CNS disorders, or CNS neoplasms (benign and malignant) * Females who are pregnant or breastfeeding * Females of childbearing potential who are not willing to use a highly effective method of contraception from the time of informed consent through the protocol-specified duration * Contraindication to fludarabine or cyclophosphamide * History of allergy or hypersensitivity to any trial agent or trial drug components * Life expectancy \< 12 weeks Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD)-Negative Complete Response (CR) or Stringent CR (sCR) Rate at 12 Months | 12 months | Minimal residual disease (MRD)-negative CR/sCR is defined as the proportion of participants achieving CR/sCR and MRD-negative status (10\^5 cutoff) at 12 months. CR/sCR per International Myeloma Working Group (IMWG) criteria is determined by the Independent Review Committee (IRC). |
| Progression-Free Survival (PFS) | Up to 15 years | PFS is defined as the time from randomization to the first documented disease progression per International Myeloma Working Group (IMWG) criteria as determined by the Independent Review Committee (IRC), or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to 15 years | OS is defined as the time from randomization to death due to any cause. |
| Overall Response Rate (ORR) | Up to 15 years | ORR is defined as the proportion of participants who achieve a best overall response of at least PR or better (sCR, CR, very good partial response (VGPR), or PR) per the 2016 IMWG criteria as determined by the IRC. |
| Rate of Very Good Partial Response or Better | Up to 15 years | Rate of VGPR or better is defined as the proportion of participants who achieve a best overall response of sCR, CR, or VGPR per the 2016 IMWG criteria as determined by the IRC. |
| Rate of CR or Better | Up to 15 years | Rate of CR or better is defined as the proportion of participants who achieve a best overall response of CR or sCR per the 2016 IMWG criteria as determined by the IRC. |
| Time to Response (TTR) | Up to 15 years | Time to response is defined as the time from date of randomization to the earliest date when a participant achieves a best overall response of sCR, CR, VGPR, or PR per 2016 IMWG criteria as determined by the IRC. |
| Duration of response (DOR) | Up to 15 years | DOR is derived only among participants who experience an overall response (sCR, CR, VGPR, or PR) per the 2016 IMWG criteria (Kumar 2016) and is defined as the time from first overall response to disease progression per the 2016 IMWG criteria as determined by the IRC, or death from any cause, whichever occurs first. |
| Time to Progression | Up to 15 years | Time to progression (TTP) is defined as the time from randomization to the first documented disease progression per the 2016 IMWG criteria as determined by the IRC, or death due to disease progression, whichever occurs first. |
| Duration of Treatment-Free Interval | Up to 15 years | Duration of treatment-free interval is defined as time from date of anitocabtagene autoleucel infusion to date of initiation of maintenance therapy. |
| Percentage of Participants Experiencing Serious Adverse Events (SAEs) | Enrollment up to 15 years | — |
| Percentage of Participants Experiencing Adverse Events (AEs) | Enrollment up to 15 years | — |
| Percentage of Participants With Anti-Anitocabtagene Autoleucel Chimeric Antigen Receptor (CAR) Antibodies (Anitocabtagene Autoleucel Arm B) | Up to 15 years | — |
| Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores | Baseline, up to 5 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, and one combined global health status/global quality of life (QoL) scale. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status /Global QoL scale indicate a higher level of functioning and a better QoL (ie, a better state of the participant), respectively, whereas higher scores in symptom scales represent a higher level of symptoms (ie, a worse state of the participant). |
| Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) - Multiple Myeloma Module (EORTC QLQ-MY20) Score | Baseline, up to 5 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 (EuroQol) 5-Dimension 5-Level (EQ-5D-5L) Scale index Score and VAS Scale Score | Baseline, up to 5 years | The EuroQol EQ-5D-5L questionnaire is a generic measure of health status with two components: the EQ-5D descriptive system and the EQ visual analog scale (VAS). The descriptive system can be used to estimate a single index value through application of a tariff of values based on direct valuations of health. The index typically ranges from 0 to 1 where a higher score indicates a better outcome. The VAS is a 20-cm VAS for recording self-rated current HRQoL state where a score of 0 represents ("the worst health you can imagine") and a score of 100 represents ("the best health you can imagine"). |
| Percentages of Participants With Responses for Patient Global Impression Scale - Severity (PGI-S) | Screening, up to 1 year | The PGI-S is a 5-point, single-item measure that assesses a patient's perception of disease symptom severity at a point in time. |
| Percentages of Participants Responses for Patient Global Impression Scale Change (PGI-C) | Screening, up to 1 year | The PGI-C is a 7-point, single-item measure that evaluates patients' perceptions of change in their symptoms over time. |
| Percentages of Participants With Responses for Functional Assessment of Cancer Therapy Item GP5 (FACT-GP5) | Screening, up to 2 years | The FACT-GP5 is a single-item question for assessing global treatment side effect bother from a patient's perspective. |
| Percentage of Participants Hospitalizations, Inpatient Days, Intensive Care Unit Days, and Reasons for Hospitalization | Up to 15 years | — |
Contacts
CONTACTMedical Information
STUDY_CHAIRKite Study Director
Kite, A Gilead Company
Outcome results
None listed