The purpose of this study is to compare the efficacy of ciltacabtagene autoleucel (cilta-cel) with standard therapy, either Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
419
Cilta-cel infusion will be administered at a target dose of 0.75 \* 10\^6 CAR-positive viable T cells/kilogram (kg).
Pomalidomide 4 mg will be administered orally.
Bortezomib 1.3 milligram per meter square (mg/m\^2) will be administered subcutaneously (SC).
Dexamethasone 20 mg/day (10mg/day for participants \>75 years of age) (on bortezomib treatment days and the days following bortezomib treatment) will be administered orally in PVd treatment; and orally or intravenous (IV) at 40 mg weekly (20mg weekly for participants \>75 years of age) in DPd treatment.
Daratumumab 1800 mg will be administered SC.
University of Alabama at Birmingham
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Stanford, California, United States
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Yale New Haven Hospital
New Haven, Connecticut, United States
Progression Free Survival (PFS)
PFS: defined as time from date of randomization to date of first documented progressed disease (PD) as per International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurred first. PD: increase of 25% from lowest response value: serum and urine M-component (absolute increase must be \>=0.5 grams per deciliter \[g/dL\] and \>=200 milligrams \[mg\] per 24 hours, respectively); only in participants without measurable serum and urine M-protein levels, difference between involved and uninvolved free light chain (FLC) levels (absolute increase of \>10 mg/dL); only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell (PC)% (absolute increase of \>=10%), appearance of new lesion; definite development of new bone lesions or definite increase in size of existing bone lesions, \>=50% increase in circulating PCs (minimum of 200 cells per microliter \[uL\]) if this was only measure of disease.
Time frame: From randomization (Day 1) to either progressive disease or death, whichever occurred first (up to 3.9 years)
Percentage of Participants Who Achieved Complete Response (CR) or Stringent Complete Response (sCR)
Time frame: From randomization (Day 1) up to 7 years
Percentage of Participants Who Achieved Overall Minimal Residual Disease (MRD) Negative Status (at 10^-5)
Time frame: From randomization (Day 1) up to 7 years
Percentage of Participants Who Were in CR or sCR and Achieved MRD-negative Status at 12 Months +/-3 Months
Time frame: From randomization (Day 1) up to 12 months +/- 3 months
Percentage of Participants Who Achieved Sustained MRD-negative Status
Time frame: From randomization (Day 1) up to 7 years
Overall Survival (OS)
Time frame: From randomization (Day 1) up to 7 years
Time to Worsening of Symptoms Using the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Total Symptom Score
Time frame: From randomization (Day 1) up to 7 years
Overall Response Rate (ORR)
Time frame: From randomization (Day 1) up to 7 years
Progression Free Survival on Next-line Therapy (PFS2)
Time frame: From randomization (Day 1) up to 7 years
Number of Participants With Treatment-emergent Adverse Events (AEs)
Time frame: From Cycle 1 Day 1 up to 7 years
Number of Participants With Treatment-emergent Adverse Events (AEs) by Severity
Time frame: From Cycle 1 Day 1 up to 7 years
Change From Baseline in Systemic Cytokine Concentrations on Participants Who Received Cilta-cel as Study Treatment (Arm B)
Time frame: From baseline (Cycle 1 Day 1) up to 7 years
Change From Baseline in Levels of CAR-T Cell Activation Markers on Participants Who Received Cilta-cel as Study Treatment (Arm B)
Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
Change From Baseline in Levels of JNJ-68284528 T Cell Expansion (Proliferation), and Persistence on Participants Who Received Cilta-cel as Study Treatment (Arm B)
Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
Number of Participants With Anti-JNJ-68284528 Antibodies on Participants Who Received Cilta-cel as Study Treatment (Arm B)
Time frame: From Cycle 1 Day 1 up to 7 years
Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 Item (EORTC-QLQ-C30) Scale Score
Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
Change From Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore
Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
Change From Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Scale Score
Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
Change From Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
Time frame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
Number of Participants in Health-Related Quality of Life as Assessed by The Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item
Time frame: From randomization (Day 1) up to 7 years
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