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.
To evaluate the overall minimal residual disease (MRD) negative rate of subjects who receive JNJ-68284528.
- Rutgers Cancer Institute of New Jersey
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
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.