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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Cellular Therapy
CAR-T Therapy
BCMA CAR-T
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-10-21
Enrollment: 237
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.


Eligibility criteria: 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

Primary outcomes:
measure: Cohorts A, B, C, D, E, and F: Percentage of Participants with Negative Minimal Residual Disease (MRD)
timeFrame: At least 1 year after JNJ-68284528 infusion on Day 1
measure: Cohorts G and H: Percentage of Participants with Sustained MRD Negative Complete Response (CR)
timeFrame: At least 1 year after JNJ-68284528 infusion on Day 1
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years and 6 months
measure: Cohorts A, B, C, D, E, and F: VGPR or Better Rate
timeFrame: Up to 2 years and 6 months
measure: Cohorts A, B, C, D, E, and F: Clinical Benefit Rate (CBR)
timeFrame: Up to 2 years and 6 months
measure: Duration of Response (DOR)
timeFrame: Up to 2 years and 6 months
measure: Time to Response (TTR)
timeFrame: Up to 2 years and 6 months
measure: Cohorts A, B, C, D, E, and F: MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR)
timeFrame: 12 months
measure: Time to MRD Negativity
timeFrame: Up to 2 years and 6 months
measure: Duration of MRD Negativity
timeFrame: Up to 2 years and 6 months
measure: Cohorts A, B, C, D, E, and F: MRD Negative Rate Across Clinical Response
timeFrame: Up to 2 years and 6 months
measure: Number of Participants with Adverse Events by Severity
timeFrame: Up to 2 years and 6 months
measure: Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability
timeFrame: Up to 2 years and 6 months
measure: Number of Participants with Laboratory Abnormalities
timeFrame: Up to 2 years and 6 months
measure: Number of Participants with Vital Signs Abnormalities
timeFrame: Up to 2 years and 6 months
measure: Cohorts A, B, C, D, E, and F: Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA
timeFrame: Up to 1 year
measure: Cohorts A, B, C, D, E, and F: Systemic Inflammatory Cytokine Concentrations
timeFrame: Up to 1 year
measure: Cohorts A, B, C, D, E, and F: Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence
timeFrame: Up to 1 year
measure: Cohorts A, B, C, D, E, and F: Number of Participants with Anti-JNJ-68284528 Antibodies
timeFrame: Up to 1 year
measure: Cohorts G and H: Percentage of Participants with Complete Response (CR) or Better
timeFrame: Up to 2 years 6 months
measure: Cohorts G and H: Percentage of Participants with MRD-negative CR or sCR
timeFrame: Up to 2 years 6 months
measure: Cohorts G and H: Progression-free Survival on Next-line Therapy (PFS2)
timeFrame: Up to 2 years and 6 months
measure: Cohorts G and H: Overall Survival (OS)
timeFrame: Up to 2 years and 6 months
measure: Cohorts G and H: Progression-free Survival (PFS)
timeFrame: Up to 2 years and 6 months
measure: Cohorts G and H: Number of Participants with Measurable Replication Competent Lentivirus (RCL) in Whole Blood
timeFrame: Up to 2 years and 6 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University Of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute, Carolinas HealthCare System
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health And Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University - Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Lille
country: France
facility: CHRU de Lille Hopital Claude Huriez
city: Nantes
country: France
facility: C.H.U. Hotel Dieu - France
city: Paris cedex 10
country: France
facility: Hopital Saint Louis
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Ramat Gan
country: Israel
facility: Sheba Medical Center Tel Hashomer
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Cohen AD, Mateos MV, Cohen YC, Rodriguez-Otero P, Paiva B, van de Donk NWCJ, Martin T, Suvannasankha A, De Braganca KC, Corsale C, Schecter JM, Varsos H, Deraedt W, Wang L, Vogel M, Roccia T, Xu X, Mistry P, Zudaire E, Akram M, Nesheiwat T, Pacaud L, Avivi I, San-Miguel J. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023 Jan 19;141(3):219-230. doi: 10.1182/blood.2022015526.