Multiple Myeloma
Conditions
Brief summary
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).
Interventions
DRUGCilta-cel
Cilta-cel infusion will be administered at a target dose of 0.75 \* 10\^6 CAR-positive viable T cells/kilogram (kg).
DRUGPomalidomide
Pomalidomide 4 mg will be administered orally.
DRUGBortezomib
Bortezomib 1.3 milligram per meter square (mg/m\^2) will be administered subcutaneously (SC).
DRUGDexamethasone
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.
DRUGDaratumumab
Daratumumab 1800 mg will be administered SC.
Sponsors
Janssen Research & Development, LLC
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
* Measurable disease at screening as defined by any of the following: (a) Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 0.5 gram per deciliter (g/dL) or urine M-protein level \>=200 milligram (mg)/24 hours; or (b) Light chain multiple myeloma without measurable M-protein in the serum or the urine: Serum free light chain \>=10 mg/dL and abnormal serum free light chain ratio * Have received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) * Have documented evidence of PD by International Myeloma Working Group (IMWG) criteria based on investigator's determination on or within 6 months of their last regimen * Be refractory to lenalidomide per IMWG consensus guidelines (failure to achieve minimal response or progression on or within 60 days of completing lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion. For participants with more than 1 prior line of therapy, there is no requirement to be lenalidomide refractory to the most recent line of prior therapy. However, participants must be refractory to lenalidomide in at least one prior line * Have clinical laboratory values meeting the following criteria during the Screening Phase (re testing is allowed but the below criteria must be met in the latest test prior to randomization): 1. Hemoglobin \>=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted); 2. Absolute neutrophil count (ANC) \>=1 \* 10\^9 per liter (L) (without recombinant human granulocyte colony-stimulating factor \[G-CSF\] within 7 days and without pegylated G-CSF within 14 days of the laboratory test); 3. Platelet count \>=75 \* 10\^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom less than (\<) 50 percent (%) of bone marrow nucleated cells are plasma cells; platelet count \>=50 \* 10\^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom \>=50% of bone marrow nucleated cells are plasma cells; 4. Lymphocyte count \>=0.3 \* 10\^9/L; 5. Aspartate aminotransferase (AST) less than or equal to (\<=)3 \* upper limit of normal (ULN); 6. Alanine aminotransferase (ALT) \<=3 \* ULN; 7. Total bilirubin \<=2.0 \* ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin \<=1.5 \* ULN is required); 8. Estimated glomerular filtration rate \>=40 milliliter per minute (mL/min) per 1.73 meter square (m\^2) (to be calculated using the Modification of Diet in Renal Disease \[MDRD\] formula)
Exclusion criteria
* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy directed at any target * Any previous therapy that is targeted to B-cell maturation antigen (BCMA) * Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia * Participants with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive pomalidomide, bortezomib, and dexamethasone (PVd) as standard therapy or bridging therapy; however, participants may receive daratumumab, pomalidomide, and dexamethasone (DPd) as standard therapy or bridging therapy * Received a cumulative dose of corticosteroids equivalent to \>=70 mg of prednisone within the 7 days prior to randomization * Monoclonal antibody treatment within 21 days * Cytotoxic therapy within 14 days * Proteasome inhibitor therapy within 14 days * Immunomodulatory drug (IMiD) therapy within 7 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization (Day 1) to either progressive disease or death, whichever occurred first (up to 3.9 years) | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Achieved Complete Response (CR) or Stringent Complete Response (sCR) | From randomization (Day 1) up to 7 years |
| Percentage of Participants Who Achieved Overall Minimal Residual Disease (MRD) Negative Status (at 10^-5) | 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 | From randomization (Day 1) up to 12 months +/- 3 months |
| Percentage of Participants Who Achieved Sustained MRD-negative Status | From randomization (Day 1) up to 7 years |
| Overall Survival (OS) | 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 | From randomization (Day 1) up to 7 years |
| Overall Response Rate (ORR) | From randomization (Day 1) up to 7 years |
| Progression Free Survival on Next-line Therapy (PFS2) | From randomization (Day 1) up to 7 years |
| Number of Participants With Treatment-emergent Adverse Events (AEs) | From Cycle 1 Day 1 up to 7 years |
| Number of Participants With Treatment-emergent Adverse Events (AEs) by Severity | 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) | 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) | 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) | 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) | 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 | 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 | 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 | 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 | 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 | From randomization (Day 1) up to 7 years |
Countries
Australia, Belgium, Denmark, France, Germany, Greece, Israel, Italy, Japan, Netherlands, Poland, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
Currently results are reported until the primary completion date (01-May-2024). Results of remaining duration of the study will be reported after study completion.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Standard Therapy: PVd or DPd Participants received either PVd or DPd as standard therapy. In pomalidomide, bortezomib and dexamethasone (PVd) treatment, participants received pomalidomide 4 milligrams (mg) orally (PO) on Days 1 to 14 in each treatment cycle; bortezomib 1.3 mg/meter square (m\^2) subcutaneous (SC) injection on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards); and dexamethasone 20 mg (or 10 mg for participants aged greater than \[\>\] 75 years) PO on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each treatment cycle of 21 days. In daratumumab, pomalidomide and dexamethasone (DPd) treatment, participants received daratumumab 1800 mg SC injection weekly on Days 1, 8, 15 and 22 (Cycle 1 and 2), every 2 weeks on Days 1 and 15 (Cycle 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); pomalidomide 4 mg PO on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg (or 20 mg for participants aged \>75 years) PO or intravenous(IV) weekly during Cycle 1-2 on Days 1, 8, 15, and 22 or split with 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23. Each treatment cycle of 28 days. Participants continued to receive PVd or DPd until confirmed progressive disease (PD), death, intolerable toxicity, withdrawal of consent, or end of study, whichever occurred earlier. | 211 |
| Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel]) Participants received at least one cycle of bridging therapy, that is PVd: pomalidomide 4 mg PO on Days 1 to 14, bortezomib 1.3 mg/m\^2 SC injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg (or 10 mg for participants aged \>75 years) PO on Days 1, 2, 4, 5, 8, 9, 11, and 12; each treatment cycle of 21 days. DPd: daratumumab SC 1800 mg (co-formulated with rHuPH20) weekly on Days 1, 8, 15, and 22, pomalidomide 4 mg PO on Days 1 to 21, and dexamethasone PO or IV 40 mg (or 20 mg for participants aged \>75 years) weekly during Cycle 1-2 on Days 1, 8, 15, and 22 or split with 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23. Each treatment cycle of 28 days. Additional cycles of bridging therapy was considered based on participant's clinical status and timing of availability of JNJ-68284528 (cilta-cel). Followed by bridging therapy, participants received conditioning regimen: cyclophosphamide 300 mg/m\^2 IV and fludarabine 30 mg/m\^2 IV daily, for 3 days on chimeric antigen receptor T cells (CAR-T) Day -5, -4, -3 (prior to JNJ-68284528 infusion), followed by JNJ-68284528 (cilta-cel) infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells per kilogram (kg) 5 to 7 days after the start of conditioning regimen. | 208 |
| Total | 419 |
Baseline characteristics
| Characteristic | Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel]) | Total | Arm A: Standard Therapy: PVd or DPd |
|---|---|---|---|
| Age, Continuous | 59.7 Years STANDARD_DEVIATION 10.09 | 60.1 Years STANDARD_DEVIATION 9.6 | 60.4 Years STANDARD_DEVIATION 9.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 28 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 152 Participants | 317 Participants | 165 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 38 Participants | 74 Participants | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 36 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 13 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 28 Participants | 54 Participants | 26 Participants |
| Race (NIH/OMB) White | 157 Participants | 314 Participants | 157 Participants |
| Sex: Female, Male Female | 92 Participants | 179 Participants | 87 Participants |
| Sex: Female, Male Male | 116 Participants | 240 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 83 / 211 | 50 / 208 |
| other Total, other adverse events | 207 / 208 | 208 / 208 |
| serious Total, serious adverse events | 98 / 208 | 98 / 208 |
Outcome results
Primary
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)
Population: The intent-to-treat (ITT) analysis set included all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Standard Therapy: PVd or DPd | Progression Free Survival (PFS) | 11.79 months |
| Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel]) | Progression Free Survival (PFS) | NA months |
Secondary
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)
Secondary
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)
Secondary
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)
Secondary
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)
Secondary
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)
Secondary
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)
Secondary
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
Secondary
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
Secondary
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
Secondary
Number of Participants With Treatment-emergent Adverse Events (AEs)
Time frame: From Cycle 1 Day 1 up to 7 years
Secondary
Number of Participants With Treatment-emergent Adverse Events (AEs) by Severity
Time frame: From Cycle 1 Day 1 up to 7 years
Secondary
Overall Response Rate (ORR)
Time frame: From randomization (Day 1) up to 7 years
Secondary
Overall Survival (OS)
Time frame: From randomization (Day 1) up to 7 years
Secondary
Percentage of Participants Who Achieved Complete Response (CR) or Stringent Complete Response (sCR)
Time frame: From randomization (Day 1) up to 7 years
Secondary
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
Secondary
Percentage of Participants Who Achieved Sustained MRD-negative Status
Time frame: From randomization (Day 1) up to 7 years
Secondary
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
Secondary
Progression Free Survival on Next-line Therapy (PFS2)
Time frame: From randomization (Day 1) up to 7 years
Secondary
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