CLINICAL TRIAL / NCT04133636
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
- Interventional
- Active
- NCT04133636
Contact Information
A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma
The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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
- 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
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
- 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