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
- Conditions
- Multiple Myeloma / symptomatic plasma cell disorder10018865
- Registration Number
- NL-OMON52781
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 9
- 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 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 4 to 8 cycles of initial therapy as specified below.
The dose/schedule of cycles administered will be as per standard of care. Up to
1 cycle of the regimens specified may not include one agent listed (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; daratumumab, lenalidomide and dexamethasone (D-Rd) or; a
carfilzomib-based triplet or quadruplet regimen - 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
- 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint:<br /><br>- MRD negative rate at a 10-5 threshold as defined by the International Myeloma<br /><br>Working Group (IMWG) criteria using next generation sequencing<br /><br>(NGS)</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Response Rates and clinical benefit rates per IMWG criteria<br /><br>- Duration of response (DOR) and time to response (TTR)<br /><br>- MRD negative rate at 12 months for subjects who achieved a complete response<br /><br>(CR MRD neg 12 month)<br /><br>- Time to MRD negativity, duration of MRD negativity, MRD negative rate across<br /><br>clinical response groups (CR, stringent complete response [sCR], very good<br /><br>partial response [VGPR])<br /><br>- Incidence and severity of adverse events, laboratory results, and other<br /><br>safety parameters<br /><br>- Pharmacokinetic and pharmacodynamic markers<br /><br>- Presence of anti- JNJ-68284528 antibodies</p><br>