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A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1)

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ClinicalTrials.gov Identifier: NCT03548207
Recruitment Status : Active, not recruiting
First Posted : June 7, 2018
Last Update Posted : December 31, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE May 25, 2018
First Posted Date  ICMJE June 7, 2018
Last Update Posted Date December 31, 2020
Actual Study Start Date  ICMJE June 29, 2018
Estimated Primary Completion Date February 24, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2019)
  • Phase 1b: Number of Participants with Adverse Events [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    An adverse event 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.
  • Phase 1b: Number of Participants with Adverse Events by Severity [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    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 should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.
  • Phase 2: Overall Response Rate (ORR) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to International Myeloma Working Group (IMWG) criteria as assessed by the Independent Review Committee (IRC).
Original Primary Outcome Measures  ICMJE
 (submitted: May 25, 2018)
  • Phase 1b: Number of Participants with Adverse Events [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    An adverse event 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.
  • Phase 1b: Number of Participants with Adverse Events by Severity [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    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), which will be graded according to the CRS revised grading system (Grade 1 to Grade 5) where Grade 1 being mild, asymptomatic or mild symptoms and Grade 5 indicating death related to adverse event.
  • Phase 2: Overall Response Rate (ORR) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to International Myeloma Working Group (IMWG) criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2019)
  • Phase 2: Number of Participants with Adverse Events [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    An adverse event 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.
  • Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    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.
  • Systemic Cytokine Concentrations [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Serum cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-g]) will be measured for biomarker assessment.
  • Levels of CAR-T Cells [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    CAR-T cells 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.
  • Level of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
  • Number of Participants with Anti-JNJ-68284528 Antibodies [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.
  • Very Good Partial Response (VGPR) or Better Rate [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    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. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (<) 100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.
  • Percentage of Participants who Achieve Clinical Benefit Rate [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Clinical benefit rate is the CR + VGPR + PR + minimal response [MR] based on IMWG defined response criteria.
  • Duration of Response (DOR) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.
  • Progression-free Survival (PFS) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    PFS defined as time from date of initial infusion of JNJ-68284528 to date of first documented disease progression, or death due to any cause, whichever occurs first. IMWG criteria for PD: Increase of 25% from lowest response value in anyone of following: Serum M-component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas.
  • Overall Survival (OS) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    OS is measured from the date of the initial infusion of JNJ-68284528 to the date of the participant's death.
  • Percentage of Participants With Negative Minimal Residual Disease (MRD) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    MRD negative rate is defined as the proportion of participants who achieve MRD negative status by the respective time point. MRD negativity will be evaluated as a potential surrogate for PFS and OS in multiple myeloma treatment.
  • Time to Response (TTR) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    TTR is defined as the time between date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.
  • Change from Baseline in Health-related Quality of Life (HRQoL) as Measured by EORTC QLQ-C30 [ Time Frame: Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1) ]
    HRQoL will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) items. Subscale and single item scores are reported on a 0-100 scale with higher scores representing better global health status, better functioning, and worst symptoms.
  • Change from Baseline in HRQoL as Measured by EORTC QLQ-MY20 [ Time Frame: Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1) ]
    HRQoL will be assessed by the EORTC QLQ-Multiple Myeloma ((MY20) module items. Subscale and single item scores are reported on a 0-100 scale with higher scores representing better global health status, better functioning, and worst symptoms.
  • Change from Baseline in Participant-reported Health Status Measured by EQ-5D-5L [ Time Frame: Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1) ]
    Participant-reported health status measured by the EuroQol Group 5-dimension, 5-level (EQ-5D-5L) questionnaire. A total utility score is reported based on the health status, ranging from 0 to 1, where higher values indicate better health utility. The visual analog scale ranges from 0 to 100 where higher values indicate better overall health status.
  • Change from Baseline in Global Health Status Using PGIC Scale [ Time Frame: Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1) ]
    Global health status as measured by the Patient Global Impression of Change (PGIC) scale in overall health. The PGIC is a single verbal rating scale ranging from 1 = a lot better now to 7 = a lot worse now.
  • Change from Baseline in Pain Measured by PGIS Scale [ Time Frame: Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1) ]
    Participant reported pain measured by Patient Global Impression of Severity (PGIS) Scale. The PGIS is a single item to assess pain severity. The 5-point verbal rating scale ranged from 1 (none) to 5 (very severe).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 25, 2018)
  • Phase 2: Number of Participants with Adverse Events [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    An adverse event 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.
  • Chimeric Antigen Receptor T (cells) (CAR-T) Positive Cellular Concentration of JNJ-68284528 [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Post-dose blood and bone marrow samples will be analyzed to determine CAR-T positive cellular concentration.
  • Transgene Levels of JNJ-68284528 [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Transgene levels of JNJ-68284528 using specific and sensitive assay methods will be assessed.
  • Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    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.
  • Systemic Cytokine Concentrations [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Serum cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-g]) will be measured for biomarker assessment.
  • Immune Related Proteins Levels [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Immune related proteins (such as perforin and granzymes) levels will be assessed.
  • Levels of CAR-T cell Activation Markers [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    CAR-T cell activation markers including, but not limited to, CD4+, CD8+, 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.
  • Level of JNJ-68284528 CAR-T cell Expansion (proliferation), and Persistence [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Levels of JNJ-68284528 CAR-T cell expansion (proliferation), and persistence will be reported.
  • Number of Participants with Anti-JNJ-68284528 Antibodies [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.
  • Very Good Partial Response (VGPR) or Better Rate [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    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. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (<) 100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.
  • Percentage of Participants who Achieve Clinical Benefit Rate [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    Clinical benefit rate is the CR + VGPR + PR + minimal response [MR] based on IMWG defined response criteria.
  • Duration of and Response (DOR) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.
  • Progression-free Survival (PFS) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    PFS defined as time from date of initial infusion of JNJ-68284528 to date of first documented disease progression, or death due to any cause, whichever occurs first. IMWG criteria for PD: Increase of 25% from lowest response value in anyone of following: Serum M-component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
  • Overall Survival (OS) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    OS is measured from the date of the initial infusion of JNJ-68284528 to the date of the participant's death.
  • Percentage of Participants With Negative Minimal Residual Disease (MRD) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    MRD negative rate is defined as the proportion of participants who achieve MRD negative status by the respective time point. MRD negativity will be evaluated as a potential surrogate for PFS and OS in multiple myeloma treatment.
  • Time to Response (TTR) [ Time Frame: Minimum 2 years after JNJ-68284528 infusion (Day 1) ]
    TTR is defined as the time between date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE A Phase 1b-2, Open-Label Study of JNJ-68284528, A Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Relapsed or Refractory Multiple Myeloma
Brief Summary The purpose of the study is to characterize safety of JNJ-68284528 and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of JNJ-68284528 (Phase 2).
Detailed Description This study will evaluate the safety and efficacy of JNJ-68284528. The study will include two phases. In Phase1b the study will enroll adults with multiple myeloma with interval assessments for potential dose escalation or de-escalation in subsequent participants. The dose selected at the completion of phase 1b will be used in Phase 2. Following consent, enrolled participants will undergo an apheresis procedure to collect cells for manufacture of investigational drug product (JNJ-68284528). Following manufacture of the drug product, participants will undergo lymphodepletion prior to infusion of JNJ-68284528. Participants will be followed for at least 2 years after study drug infusion, with long-term 15 year follow-up on a separate study. The study will evaluate safety, biomarkers, pharmacokinetic/pharmacodynamic evaluations and efficacy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Biological: 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).
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 8, 2020)
126
Original Estimated Enrollment  ICMJE
 (submitted: May 25, 2018)
84
Estimated Study Completion Date  ICMJE April 30, 2022
Estimated Primary Completion Date February 24, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
  • Have measurable disease at Screening as defined by any of the following a) Serum monoclonal paraprotein (M-protein) level more than or equal to (>=) 1.0 gram per deciliter(g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24hr); or b) Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
  • Have received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) (refractory multiple myeloma as defined by IMWG consensus criteria). Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single lines of therapy a) Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease (PD) was the best response to the regimen
  • Have received as part of previous therapy a PI, an IMiD, and an anti-CD38 antibody
  • Participant must have documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria on or within 12 months of their last line of therapy. Confirmation may be from either central or local testing. Also, participants with documented evidence of progressive disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible
  • Have Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1

Exclusion Criteria:

  • Have received prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
  • Have received any therapy that is targeted to B-cell maturation antigen (BCMA)
  • Have following cardiac conditions: a) New York Heart Association (NYHA) stage III or IV congestive heart failure b) Myocardial infarction or coronary artery bypass graft (CABG) less than or equal to (<=) 6 months prior to enrollment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) History of severe non-ischemic cardiomyopathy e) Impaired cardiac function (left ventricular ejection fraction [LVEF] less than [<]45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed less than or equal to (<=) 8 weeks of apheresis)
  • Received a cumulative dose of corticosteroids equivalent to >= 70 mg of prednisone within the 7 days prior to apheresis
  • Have received either of the following: a) An allogenic stem cell transplant within 6 months before apheresis. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD) b) An autologous stem cell transplant less than or equal to (<=) 12 weeks before apheresis
  • Have known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan,   United States
Removed Location Countries Belgium,   France,   Israel,   Netherlands,   Spain
 
Administrative Information
NCT Number  ICMJE NCT03548207
Other Study ID Numbers  ICMJE CR108480
2018-000121-32 ( EudraCT Number )
68284528MMY2001 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP