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

Multiple Myeloma Clinical Trial

— CARTITUDE-2  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04133636
• Other study ID #: CR108581
• Secondary ID: 2018-004124-1068
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 7, 2019
• Est. completion date: November 13, 2028

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 169
• Est. completion date: November 13, 2028
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

• 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• JNJ-68284528
Participants in Cohorts A,B,C, D, E, F, G, and H will receive JNJ-68284528 intravenously.
• Lenalidomide
Some participants in Cohort D and all participants in Cohorts E, G, and H will also receive lenalidomide capsules orally.
• Daratumumab
Participants in Cohorts E, G, and H will also receive daratumumab subcutaneous (SC) injection.
• Bortezomib
Participants in Cohorts E and H will also receive bortezomib subcutaneously.
• Dexamethasone
Participants in Cohorts E, G, and H will also receive dexamethasone orally or intravenously.

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
France	CHRU de Lille Hopital Claude Huriez	Lille
France	C.H.U. Hotel Dieu - France	Nantes
France	Hopital Saint Louis	Paris cedex 10
Germany	Universitaetsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitatsklinikum Wurzburg	Wuerzburg
Israel	Sheba Medical Center Tel Hashomer	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Riyadh
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp Clinico Univ de Salamanca	Salamanca
United States	Emory University	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Levine Cancer Institute, Carolinas HealthCare System	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Israel,  Netherlands,  Saudi Arabia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohorts A, B, C, D, E, and F: Percentage of Participants with Negative Minimal Residual Disease (MRD)	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.	At least 1 year after JNJ-68284528 infusion on Day 1
Primary	Cohorts G and H: Percentage of Participants with Sustained MRD Negative Complete Response (CR)	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.	At least 1 year after JNJ-68284528 infusion on Day 1
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.	Up to 2 years and 6 months
Secondary	Cohorts A, B, C, D, E, and F: VGPR or Better Rate	The VGPR or better rate (stringent complete responses [sCR] + complete response [CR] + VGPR), defined as the percentage of participants achieving VGPR or better response according to IMWG criteria during or after the study treatment.	Up to 2 years and 6 months
Secondary	Cohorts A, B, C, D, E, and F: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.	Up to 2 years and 6 months
Secondary	Duration of Response (DOR)	DOR will be calculated among responders from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria.	Up to 2 years and 6 months
Secondary	Time to Response (TTR)	TTR is defined as the time from the date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.	Up to 2 years and 6 months
Secondary	Cohorts A, B, C, D, E, and F: MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR)	MRD negative rate at 12 months for participants who achieved a complete response (CR) is defined as the percentage of participants who are MRD negative by bone marrow aspirate and meet the IMWG criteria for CR at 12 months after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy including retreatment of JNJ-68284528.	12 months
Secondary	Time to MRD Negativity	Time to MRD negativity will be calculated in participants who are MRD negative by bone marrow aspirate from the date of the initial infusion of JNJ-68284528 to the initial date of reaching the MRD negative status.	Up to 2 years and 6 months
Secondary	Duration of MRD Negativity	Duration of MRD negativity will be calculated among participants who are MRD negative by bone marrow aspirate from the date of initial MRD negativity to the date when MRD is detected at the same threshold (10^-5).	Up to 2 years and 6 months
Secondary	Cohorts A, B, C, D, E, and F: MRD Negative Rate Across Clinical Response	MRD negative rate across clinical response groups will be assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR) or very good partial response (VGPR) according to the IMWG criteria during or after the study treatment. MRD negative rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any timepoint.	Up to 2 years and 6 months
Secondary	Number of Participants with Adverse Events by Severity	An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.	Up to 2 years and 6 months
Secondary	Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 2 years and 6 months
Secondary	Number of Participants with Laboratory Abnormalities	Number of participants with laboratory abnormalities will be reported.	Up to 2 years and 6 months
Secondary	Number of Participants with Vital Signs Abnormalities	Number of participants with vital signs abnormalities will be reported.	Up to 2 years and 6 months
Secondary	Cohorts A, B, C, D, E, and F: Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA	Levels of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood will be reported.	Up to 1 year
Secondary	Cohorts A, B, C, D, E, and F: Systemic Inflammatory Cytokine Concentrations	Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.	Up to 1 year
Secondary	Cohorts A, B, C, D, E, and F: Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence	Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.	Up to 1 year
Secondary	Cohorts A, B, C, D, E, and F: Number of Participants with Anti-JNJ-68284528 Antibodies	Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.	Up to 1 year
Secondary	Cohorts G and H: Percentage of Participants with Complete Response (CR) or Better	CR or better is defined as the percentage of participants achieving CR or sCR prior to subsequent antimyeloma therapy in accordance with the IMWG criteria during or after the study treatment.	Up to 2 years 6 months
Secondary	Cohorts G and H: Percentage of Participants with MRD-negative CR or sCR	MRD-negative CR/sCR is defined as the percentage of participants who achieve MRD-negative status, as determined by NGS/NGF with sensitivity of 10^-5, at any time after enrollment and prior to progressive disease or subsequent antimyeloma therapy and who achieve CR/sCR or better.	Up to 2 years 6 months
Secondary	Cohorts G and H: Progression-free Survival on Next-line Therapy (PFS2)	PFS2 is defined as the time interval between the start of study treatment and date of event, which is defined as death from any cause or PD as assessed by investigator that starts after the next line of therapy, whichever occurs first.	Up to 2 years and 6 months
Secondary	Cohorts G and H: Overall Survival (OS)	OS is defined as the time from the start of study treatment to the date of the participant's death.	Up to 2 years and 6 months
Secondary	Cohorts G and H: Progression-free Survival (PFS)	PFS is defined as the time from the start of study treatment to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.	Up to 2 years and 6 months
Secondary	Cohorts G and H: Number of Participants with Measurable Replication Competent Lentivirus (RCL) in Whole Blood	Number of participants with measurable RCL in whole blood will be reported.	Up to 2 years and 6 months