A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT04133636
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 237
- 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 milligrams 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 total copies) in at least 20 percent (%) of the total plasma cell population
- 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
- Received initial therapy as specified below. The dose/schedule of cycles administered will be as per standard of care. It is acceptable for up to 1 cycle of the protocol-specified regimens to be missing one of the listed agents (example, held due to toxicity). Acceptable combinations include: At least 5 to 8 cycles of initial therapy with daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd). The dose/schedule of cycles administered will be as per standard of care or; at least 4 to 8 cycles of initial therapy with daratumumab, lenalidomide and dexamethasone (D-Rd) or; at least 4 to 8 cycles of initial therapy with a carfilzomib-based triplet or quadruplet regimen
- Cohort G: Not considered for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to: a) Ineligibility due to advanced age; or b) Ineligibility due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or c) Subject refusal of high-dose chemotherapy with ASCT as initial treatment
- Cohort H: Considered a candidate for high-dose chemotherapy with ASCT as initial treatment
- Cohorts A, B, C, E, G, H:
- Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligrams (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, G, H: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
- 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
- Cohorts F, G, and H: Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: a) non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured; b) skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; c) non-invasive cervical cancer treated within the last 24 months that is considered completely cured; d) localized prostate cancer (N0M0): with a Gleason score of greater than or equal to (=>)6, treated within the last 24 months or untreated and under surveillance, with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence, e) breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence; f) malignancy that is considered cured with minimal risk of recurrence
- Cohorts E, G, and H: Frailty index of >= 2 according to Myeloma Geriatric Assessment score
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description JNJ-68284528 JNJ-68284528 Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel. JNJ-68284528 Bortezomib Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel. JNJ-68284528 Dexamethasone Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel. JNJ-68284528 Lenalidomide Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel. JNJ-68284528 Daratumumab Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel.
- Primary Outcome Measures
Name Time Method Cohorts A, B, C, D, E, and F: Percentage of Participants with Negative Minimal Residual Disease (MRD) At least 1 year after JNJ-68284528 infusion on Day 1 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.
Cohorts G and H: Percentage of Participants with Sustained MRD Negative Complete Response (CR) At least 1 year after JNJ-68284528 infusion on Day 1 Sustained MRD-negative CR is defined as participants with CR or better who sustain MRD-negative status, as determined by next-generation sequencing (NGS) or next generation flowcytometry (NGF) with sensitivity of 10\^-5, for at least 12 months without any examination showing MRD positive status or progressive disease in between.
- Secondary Outcome Measures
Name Time Method Cohorts G and H: Progression-free Survival on Next-line Therapy (PFS2) Up to 2 years and 6 months PFS2 is defined as the time interval between the start of study treatment and date of event, which is defined as death from any cause or PD as assessed by investigator that starts after the next line of therapy, whichever occurs first.
Cohorts G and H: Progression-free Survival (PFS) Up to 2 years and 6 months PFS is defined as the time from the start of study treatment to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.
Duration of Response (DOR) Up to 2 years and 6 months 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.
Number of Participants with Adverse Events by Severity Up to 2 years and 6 months 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.
Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability Up to 2 years and 6 months 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.
Cohorts A, B, C, D, E, and F: Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA Up to 1 year 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.
Cohorts A, B, C, D, E, and F: Clinical Benefit Rate (CBR) Up to 2 years and 6 months CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.
Cohorts A, B, C, D, E, and F: MRD Negative Rate Across Clinical Response Up to 2 years and 6 months 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.
Number of Participants with Laboratory Abnormalities Up to 2 years and 6 months Number of participants with laboratory abnormalities will be reported.
Cohorts G and H: Percentage of Participants with MRD-negative CR or sCR Up to 2 years 6 months MRD-negative CR/sCR is defined as the percentage of participants who achieve MRD-negative status, as determined by NGS/NGF with sensitivity of 10\^-5, at any time after enrollment and prior to progressive disease or subsequent antimyeloma therapy and who achieve CR/sCR or better.
Overall Response Rate (ORR) Up to 2 years and 6 months ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.
Cohorts A, B, C, D, E, and F: VGPR or Better Rate Up to 2 years and 6 months 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.
Cohorts A, B, C, D, E, and F: MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR) 12 months 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.
Duration of MRD Negativity Up to 2 years and 6 months 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).
Number of Participants with Vital Signs Abnormalities Up to 2 years and 6 months Number of participants with vital signs abnormalities will be reported.
Time to Response (TTR) Up to 2 years and 6 months 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.
Time to MRD Negativity Up to 2 years and 6 months 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.
Cohorts A, B, C, D, E, and F: Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence Up to 1 year Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
Cohorts A, B, C, D, E, and F: Number of Participants with Anti-JNJ-68284528 Antibodies Up to 1 year Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.
Cohorts G and H: Percentage of Participants with Complete Response (CR) or Better Up to 2 years 6 months CR or better is defined as the percentage of participants achieving CR or sCR prior to subsequent antimyeloma therapy in accordance with the IMWG criteria during or after the study treatment.
Cohorts G and H: Overall Survival (OS) Up to 2 years and 6 months OS is defined as the time from the start of study treatment to the date of the participant's death.
Cohorts A, B, C, D, E, and F: Systemic Inflammatory Cytokine Concentrations Up to 1 year Blood cytokine concentrations (Interleukin \[IL\]-6, IL-15, IL-10, and Interferon \[IFN-gamma\]) will be measured for biomarker assessment.
Cohorts G and H: Number of Participants with Measurable Replication Competent Lentivirus (RCL) in Whole Blood Up to 2 years and 6 months Number of participants with measurable RCL in whole blood will be reported.
Trial Locations
- Locations (46)
Virginia Commonwealth University - Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University Of California San Diego
🇺🇸San Diego, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Levine Cancer Institute, Carolinas HealthCare System
🇺🇸Charlotte, North Carolina, United States
Oregon Health And Science University
🇺🇸Portland, Oregon, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
UZ Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
CHRU de Lille Hopital Claude Huriez
🇫🇷Lille, France
C.H.U. Hotel Dieu - France
🇫🇷Nantes, France
Hopital Saint Louis
🇫🇷Paris cedex 10, France
Universitaetsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Universitatsklinikum Wurzburg
🇩🇪Wuerzburg, Germany
Sheba Medical Center Tel Hashomer
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
King Faisal Specialist Hospital & Research Center
🇸🇦Riyadh, Saudi Arabia
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
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