Description:
The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
Recruiting
Phase 2
Drug | Synonyms | Arms |
---|---|---|
JNJ-68284528 | Ciltacabtagene autoleucel (cilta-cel) | JNJ-68284528 |
Lenalidomide | JNJ-68284528 | |
Daratumumab | JNJ-68284528 | |
Bortezomib | JNJ-68284528 | |
Dexamethasone | JNJ-68284528 |
Multiple myeloma is characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. The main aim of the study is to determine the safety and efficacy of JNJ-68284528 in various clinical settings. JNJ-68284528 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA). The study comprises of a Screening Phase (less than or equal to [<=] 28 days prior to apheresis) followed by Apheresis (will occur upon enrollment); a Treatment Phase including a conditioning regimen followed by infusion of JNJ-68284528 and post-infusion assessments from Day 1 to Day 100 (participants who receive an infusion of JNJ-68284528 should continue all subsequent assessments); and a Post-treatment Phase (Day 101 and up to the end of each study cohort). Safety evaluations will include a review of adverse events, laboratory test results, vital sign measurements, physical examination findings (including neurologic examination), assessment of cardiac function, immune effector cell-associated encephalopathy (ICE) score, handwriting assessment, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade. Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. For certain participants (those without measurable disease in serum or urine) efficacy will be assessed via imaging: positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI). The overall duration of the study is up to 2.5 years.
Name | Type | Description | Interventions |
---|---|---|---|
JNJ-68284528 | Experimental | Single group assignment-After lymphodepletion, JNJ-68284528 will be administered as single infusion to participants in cohort A (Progressive disease after 1-3 prior lines of therapy), cohort B (Early relapse after front-line), cohort C (Relapsed/refractory multiple myeloma after PI, IMiD, anti-CD38, and anti- BCMA therapy), cohort D (Less than CR after ASCT front-line therapy; some participants will be administered JNJ-68284528 followed by lenalidomide), cohort F (Newly diagnosed multiple myeloma [NDMM] with standard risk [international staging system {ISS} Stage I and II] and after initiation of therapy). Participants in cohort E (NDMM, transplant not planned, high risk disease) will first be administered with quadruplet induction regimen of daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd), followed by lymphodepletion and JNJ-68284528, followed by consolidation regimen of daratumumab and lenalidomide (D+R). |
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Inclusion Criteria: - Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide refractory per International Myeloma Working Group (IMWG) guidelines - Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease progression per IMWG criteria less than or equal to (<=) 12 months after treatment with autologous stem cell transplantation (ASCT) or <=12 months from the start of anti-myeloma therapy for participants who have not had an ASCT - Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and B-cell maturation antigen (BCMA)-directed therapy - Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation - Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle of prior therapy before enrollment is acceptable) and classified as high risk defined as either: 1) International Staging System (ISS) stage III criteria, Beta 2 microglobulin greater than or equal to (>=) 5.5 milligram per liter (mg/L) (via local or central laboratory assessment) or 2) high risk cytogenetic features del(17/17p), t (14;16), t(14;20), 1q amplification (at least 4 copies) Cohorts A, B, C, E: - Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours - Light chain multiple myeloma in whom only measurable disease is by serum free light chain (FLC) levels in the serum: Serum immunoglobulin FLC >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio - Cohort A: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole -body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. A minimum of one lesion with a bi-dimensional measurement of at least 1 centimeter (cm)*1 cm is required - Cohorts B, C: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria - Cohorts A, B, C, D, E, F: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 - Cohort F: Participant must have a documented efficacy response of very good partial response (VGPR) or better, without progressive disease prior to enrollment, as assessed per IMWG 2016 criteria Exclusion Criteria: - Cohorts A, B, D, F: Any therapy that is targeted to BCMA - Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target Cohorts A, B, C, D, F: - Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy - Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis - Serious underlying medical condition, such as (a) evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection; (b) active autoimmune disease or a history of autoimmune disease within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d) any history of Parkinson's disease or other neurodegenerative disorder - Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Measure: | Percentage of Participants with Negative Minimal Residual Disease (MRD) |
Time Frame: | At least 1 year after JNJ-68284528 infusion on Day 1 |
Safety Issue: | |
Description: | MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate as defined by the International Myeloma Working Group (IMWG) criteria. |
Measure: | Overall Response Rate (ORR) |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria. |
Measure: | VGPR or Better Rate |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | The VGPR or better rate (stringent complete responses [sCR] + complete response [CR] + VGPR), defined as the percentage of participants achieving VGPR or better response according to IMWG criteria during or after the study treatment. |
Measure: | Clinical Benefit Rate (CBR) |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria. |
Measure: | Duration of Response (DOR) |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | DOR will be calculated among responders from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria. |
Measure: | Time to Response (TTR) |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | TTR is defined as the time from the date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better. |
Measure: | MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR) |
Time Frame: | 12 months |
Safety Issue: | |
Description: | MRD negative rate at 12 months for participants who achieved a complete response (CR) is defined as the percentage of participants who are MRD negative by bone marrow aspirate and meet the IMWG criteria for CR at 12 months after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy including retreatment of JNJ-68284528. |
Measure: | Time to MRD Negativity |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | Time to MRD negativity will be calculated in participants who are MRD negative by bone marrow aspirate from the date of the initial infusion of JNJ-68284528 to the initial date of reaching the MRD negative status. |
Measure: | Duration of MRD Negativity |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | Duration of MRD negativity will be calculated among participants who are MRD negative by bone marrow aspirate from the date of initial MRD negativity to the date when MRD is detected at the same threshold (10^-5). |
Measure: | MRD Negative Rate Across Clinical Response |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | MRD negative rate across clinical response groups will be assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR) or very good partial response (VGPR) according to the IMWG criteria during or after the study treatment. MRD negative rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any timepoint. |
Measure: | Number of Participants with Adverse Events by Severity |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. |
Measure: | Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. |
Measure: | Number of Participants with Laboratory Abnormalities |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | Number of participants with laboratory abnormalities will be reported. |
Measure: | Number of Participants with Vital Sign Abnormalities |
Time Frame: | Up to 2 years and 6 months |
Safety Issue: | |
Description: | Number of participants with vital sign abnormalities will be reported. |
Measure: | Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | Levels of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood will be reported. |
Measure: | Systemic Inflammatory Cytokine Concentrations |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment. |
Measure: | Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported. |
Measure: | Number of Participants with Anti-JNJ-68284528 Antibodies |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported. |
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
August 13, 2021