Active, not recruiting
Phase 2
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
Condition(s) studied
Multiple Myeloma
Investigational drug(s) / intervention(s)
JNJ-68284528: Participants in Cohorts A,B,C, D, E, F and Cohort G (for US sites only) will receive JNJ-68284528 intravenously.
Lenalidomide: Some participants in Cohort D and all participants in Cohorts E and Cohort G (for US sites only) will also receive lenalidomide capsules orally.
Daratumumab: Participants in Cohorts E and Cohort G (for US sites only) will also receive daratumumab subcutaneous (SC) injection.
Bortezomib: Participants in Cohorts E will also receive bortezomib subcutaneously.
Dexamethasone: Participants in Cohorts E and Cohort G (for US sites only) will also receive dexamethasone orally or intravenously.
Study summary
The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
Eligibility
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 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
* For US sites only: 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
* Cohorts A, B, C, E and Cohort G (for US sites only):
* 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 and Cohort G (for US sites only): Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
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
* Cohort F and Cohort G (for US sites only): 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
* Cohort E and Cohort G (for US sites only): Frailty index of \>= 2 according to Myeloma Geriatric Assessment score
Primary outcome measure(s)
- 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.
- For US sites only: Cohort G: 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.
Trial sites (47)
| Facility | City | Region | Status |
| University Of California San Diego |
San Diego |
California |
|
| University of California San Francisco |
San Francisco |
California |
|
| Yale University School Of Medicine |
New Haven |
Connecticut |
|
| Moffitt Cancer Center |
Tampa |
Florida |
|
| Emory University |
Atlanta |
Georgia |
|
| Northwestern University |
Chicago |
Illinois |
|
| University of Chicago |
Chicago |
Illinois |
|
| Indiana University |
Indianapolis |
Indiana |
|
| University of Iowa Hospitals and Clinics |
Iowa City |
Iowa |
|
| University of Kansas Cancer Center |
Westwood |
Kansas |
|
| Norton Cancer Institute |
Louisville |
Kentucky |
|
| Dana Farber Cancer Institute |
Boston |
Massachusetts |
|
| Barbara Ann Karmanos Cancer Institute |
Detroit |
Michigan |
|
| Mayo Clinic Rochester |
Rochester |
Minnesota |
|
| Washington University School Of Medicine |
St Louis |
Missouri |
|
| Hackensack University Medical Center |
Hackensack |
New Jersey |
|
| Rutgers Cancer Institute of New Jersey |
New Brunswick |
New Jersey |
|
| Roswell Park Cancer Institute |
Buffalo |
New York |
|
| Mount Sinai Medical Center |
New York |
New York |
|
| Memorial Sloan-Kettering Cancer Center |
New York |
New York |
|
| Montefiore Medical Center |
The Bronx |
New York |
|
| Levine Cancer Institute, Carolinas HealthCare System |
Charlotte |
North Carolina |
|
| Cleveland Clinic |
Cleveland |
Ohio |
|
| Oregon Health And Science University |
Portland |
Oregon |
|
| University of Pennsylvania |
Philadelphia |
Pennsylvania |
|
| Thomas Jefferson University |
Philadelphia |
Pennsylvania |
|
| University of Pittsburgh |
Pittsburgh |
Pennsylvania |
|
| University of Texas Southwestern Medical Center |
Dallas |
Texas |
|
| University of Utah |
Salt Lake City |
Utah |
|
| University of Virginia |
Charlottesville |
Virginia |
|
| Virginia Commonwealth University - Massey Cancer Center |
Richmond |
Virginia |
|
| Fred Hutchinson Cancer Center |
Seattle |
Washington |
|
| University of Wisconsin Carbone Cancer Center |
Madison |
Wisconsin |
|
| UZ Gent |
Ghent |
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 |
France |
|
| Universitaetsklinikum Hamburg Eppendorf |
Hamburg |
Germany |
|
| Universitatsklinikum Wurzburg |
Würzburg |
Germany |
|
+ 7 more sites — see the full list on the official registry below.
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