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History of Changes for Study: 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 (CARTITUDE-2)
Latest version (submitted September 8, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 October 18, 2019 None (earliest Version on record)
2 November 27, 2019 Recruitment Status, Arms and Interventions, Study Status, Outcome Measures, Contacts/Locations, Eligibility and Study Design
3 December 24, 2019 Contacts/Locations, Study Status and Eligibility
4 January 21, 2020 Arms and Interventions, Study Design and Study Status
5 January 30, 2020 Contacts/Locations and Study Status
6 February 27, 2020 Study Status and Contacts/Locations
7 April 13, 2020 Contacts/Locations, Arms and Interventions, Study Status, Eligibility and Oversight
8 May 19, 2020 Study Status
9 June 18, 2020 Study Status and Contacts/Locations
10 July 13, 2020 Study Status and Contacts/Locations
11 August 12, 2020 Arms and Interventions, Study Status, Contacts/Locations, Eligibility, Study Design and Study Description
12 September 10, 2020 Study Status and Contacts/Locations
13 October 8, 2020 Study Status and Contacts/Locations
14 November 5, 2020 Contacts/Locations, Study Status and Study Design
15 November 23, 2020 Study Status, Contacts/Locations and Study Design
16 January 28, 2021 Study Status and Contacts/Locations
17 March 25, 2021 Study Status and Contacts/Locations
18 June 21, 2021 Arms and Interventions, Study Status, Contacts/Locations, Eligibility, Outcome Measures, Study Design and Conditions
19 July 15, 2021 Study Status and Contacts/Locations
20 August 11, 2021 Study Status and Contacts/Locations
21 September 9, 2021 Study Status and Contacts/Locations
22 October 7, 2021 Study Status and Contacts/Locations
23 November 4, 2021 Contacts/Locations and Study Status
24 December 2, 2021 Study Status
25 January 27, 2022 Study Status
26 March 28, 2022 Study Status, Contacts/Locations, Eligibility, Arms and Interventions and Study Design
27 April 21, 2022 Contacts/Locations and Study Status
28 May 19, 2022 Study Status
29 June 16, 2022 Study Status
30 July 26, 2022 Study Status and Eligibility
31 July 27, 2022 Study Status
32 August 11, 2022 Contacts/Locations and Study Status
33 September 8, 2022 Study Status
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Study NCT04133636
Submitted Date:  October 18, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: CR108581
Brief Title: 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 (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
Secondary IDs: 2018-004124-10 [EudraCT Number]
68284528MMY2003 [Janssen Research & Development, LLC]
Open or close this module Study Status
Record Verification: October 2019
Overall Status: Not yet recruiting
Study Start: October 23, 2019
Primary Completion: April 12, 2022 [Anticipated]
Study Completion: September 28, 2022 [Anticipated]
First Submitted: October 18, 2019
First Submitted that
Met QC Criteria:
October 18, 2019
First Posted: October 21, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
October 18, 2019
Last Update Posted: October 21, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Janssen Research & Development, LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
Detailed Description: Multiple myeloma is characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. The main aim of the study is to determine the safety and efficacy of JNJ-68284528 in various clinical settings. JNJ-68284528 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA). The study comprises of a Screening Phase (less than or equal to [<=] 28 days prior to apheresis) followed by Apheresis (will occur upon enrollment); a Treatment Phase including a conditioning regimen followed by infusion of JNJ-68284528 and post-infusion assessments from Day 1 to Day 100 (participants who receive an infusion of JNJ-68284528 should continue all subsequent assessments); and a Post-treatment Phase (Day 101 and up to the end of each study cohort). Safety evaluations will include a review of adverse events, laboratory test results, vital sign measurements, physical examination findings (including neurologic examination), assessment of cardiac function, immune effector cell-associated encephalopathy (ICE) score, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade. Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. The overall duration of the study is up to 2.5 years.
Open or close this module Conditions
Conditions: Multiple Myeloma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 40 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort A: Progressive Disease After 1-3 Prior Lines of Therapy
After lymphodepletion JNJ-68284528 will be administered as a single infusion.
Drug: JNJ-68284528
JNJ-68284528 consist of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).
Experimental: Cohort B: Early Relapse after Front-line Therapy
After lymphodepletion JNJ-68284528 will be administered as a single infusion.
Drug: JNJ-68284528
JNJ-68284528 consist of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percentage of Participants with Negative Minimal Residual Disease (MRD)
[ Time Frame: At least 1 year after JNJ-68284528 infusion on Day 1 ]

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.
Secondary Outcome Measures:
1. MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR)
[ Time Frame: 12 months ]

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.
2. Time to MRD Negativity
[ Time Frame: Up to 2 years ]

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.
3. Duration of MRD Negativity
[ Time Frame: Up to 2 years ]

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).
4. MRD Negative Rate Across Clinical Response
[ Time Frame: Up to 2 years ]

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.
5. Overall Response Rate (ORR)
[ Time Frame: Up to 2 years ]

ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.
6. VGPR or Better Rate
[ Time Frame: Up to 2 years ]

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.
7. Clinical Benefit Rate (CBR)
[ Time Frame: Up to 2 years ]

CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.
8. Duration of Response (DOR)
[ Time Frame: Up to 2 years ]

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.
9. Time to Response (TTR)
[ Time Frame: Up to 2 years ]

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.
10. Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability
[ Time Frame: Up to 2 years ]

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.
11. Number of Participants with Adverse Events by Severity
[ Time Frame: Up to 2 years ]

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.
12. Maximum Blood Concentration (Cmax) of JNJ-68284528
[ Time Frame: Up to 1 year ]

Cmax is defined as the maximum observed blood concentration.
13. Time to Reach Maximum Observed Blood Concentration (Tmax) of JNJ-68284528
[ Time Frame: Up to 1 year ]

Tmax is defined as actual sampling time to reach maximum observed blood concentration.
14. Time to Last Quantifiable Blood Concentration (Tlast) of JNJ-68284528
[ Time Frame: Up to 1 year ]

Tlast is defined as the time to last observed quantifiable blood concentration.
15. Area Under the Blood Concentration-Time Curve from Time Zero to Last Quantifiable Time (AUClast) of JNJ-68284528
[ Time Frame: Up to 1 year ]

The AUClast is the area under the blood concentration-time curve from time zero to last quantifiable time.
16. Area Under the Blood Concentration-Time Curve from Time Zero to Infinite Time (AUCinfinity) of JNJ-68284528
[ Time Frame: Up to 1 year ]

AUCinfinity is defined as area under the blood analyte concentration-time curve from time 0 to infinite time of JNJ-68284528.
17. Rate Constant (Lambda[z])
[ Time Frame: Up to 1 year ]

Lambda(z) is the first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
18. Elimination Half-Life (t1/2) of JNJ-68284528
[ Time Frame: Up to 1 year ]

t1/2 is defined as the time measured for the blood concentration to decrease by 1 half of its original concentration.
19. Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA
[ Time Frame: Up to 2 years ]

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.
20. Systemic Inflammatory Cytokine Concentrations
[ Time Frame: Up to 2 years ]

Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.
21. Levels of CAR-T Cell Activation Markers
[ Time Frame: Up to 2 years ]

CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry or cytometry by time of flight (CyTOF) or both and correlated with response.
22. Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence
[ Time Frame: Up to 2 years ]

Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
23. Number of Participants with Anti-JNJ-68284528 Antibodies
[ Time Frame: Up to 2 years ]

Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Cohort A: Received from 1 to 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 (<) 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
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

Exclusion Criteria:

  • Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
  • Any therapy that is targeted to B-cell maturation antigen (BCMA)
  • 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 prior to apheresis
  • Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
  • Serious underlying medical condition, such as (a) evidence of serious active viral, bacterial, 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
Open or close this module Contacts/Locations
Central Contact Person: Study Contact
Telephone: 844-434-4210
Email: JNJ.CT@sylogent.com
Study Officials: Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC
Locations: United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, North Carolina
Levine Cancer Institute, Carolinas HealthCare System
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
United States, Washington
Fred Hutchinson Cancer Center
Seattle, Washington, United States, 98109
Belgium
UZ Gent
Gent, Belgium, 9000
UZ Leuven
Leuven, Belgium, 3000
France
CHRU de Lille - Hôpital Claude Huriez
Lille, France, 59000
C.H.U. Hotel Dieu - France
Nantes, France, 44093
Germany
Universitaetsklinikum Hamburg Eppendorf
Hamburg, Germany, 20246
Universitaetsklinikum Heidelberg
Heidelberg, Germany, 69120
Universitätsklinikum Würzburg
Würzburg, Germany, 97080
Israel
Sheba Medical Center Tel Hashomer
Ramat Gan, Israel, 52621
Tel-Aviv Sourasky Medical Center
Tel-Aviv, Israel, 64239
Netherlands
VU Medisch Centrum
Amsterdam, Netherlands, 1081 HV
Spain
Clinica Univ. de Navarra
Pamplona, Spain, 31008
Hosp. Clinico Univ. de Salamanca
Salamanca, Spain, 37007
Open or close this module IPDSharing
Plan to Share IPD: Yes

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Supporting Information:
Time Frame:
Access Criteria:
URL: https://www.janssen.com/clinical-trials/transparency
Open or close this module References
Links:
Available IPD/Information:

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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services