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

NCT04133636 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: CR10858168284528MMY20032018-004124-102023-506587-13-00
• Study Type: interventional
• Target: 210
• Locations: 8 countries
• Sites: 47

Brief Summary

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

Conditions

Multiple Myeloma

Keywords

Cellular Therapy; CAR-T Therapy; BCMA CAR-T

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (23)

• Overall Response Rate (ORR)

  Up to 2 years and 6 months

• Cohorts A, B, C, D, E, and F: VGPR or Better Rate

  Up to 2 years and 6 months

• Cohorts A, B, C, D, E, and F: Clinical Benefit Rate (CBR)

  Up to 2 years and 6 months

• Duration of Response (DOR)

  Up to 2 years and 6 months

• Time to Response (TTR)

  Up to 2 years and 6 months

Study Arms (1)

JNJ-68284528

EXPERIMENTAL

Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel.

Drug: JNJ-68284528; Drug: Lenalidomide; Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone

Interventions

JNJ-68284528 DRUG

Participants in Cohorts A,B,C, D, E, F, G, and H will receive JNJ-68284528 intravenously.

Also known as: Ciltacabtagene autoleucel (cilta-cel)

JNJ-68284528

Lenalidomide DRUG

Some participants in Cohort D and all participants in Cohorts E, G, and H will also receive lenalidomide capsules orally.

JNJ-68284528

Daratumumab DRUG

Participants in Cohorts E, G, and H will also receive daratumumab subcutaneous (SC) injection.

JNJ-68284528

Bortezomib DRUG

Participants in Cohorts E and H will also receive bortezomib subcutaneously.

JNJ-68284528

Dexamethasone DRUG

Participants in Cohorts E, G, and H will also receive dexamethasone orally or intravenously.

JNJ-68284528

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (47)

University Of California San Diego

San Diego, California, 92037, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06510, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63108, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health And Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University - Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHRU de Lille Hopital Claude Huriez

Lille, 59037, France

Location

C.H.U. Hotel Dieu - France

Nantes, 44093, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Universitaetsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, 97080, Germany

Location

Sheba Medical Center Tel Hashomer

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

King Faisal Specialist Hospital & Research Center

Riyadh, 11211, Saudi Arabia

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Related Publications (1)

• 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.

  PMID: 36095849 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; daratumumab; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: October 21, 2019
• Study Start: November 7, 2019
• Primary Completion (Estimated): August 4, 2026
• Study Completion (Estimated): September 3, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); FR (3); NL (2); US (33); IL (2); BE (2); DE (2); SA (1)